Treatment-Radiotherapy Template Instructions

TREATMENT-RADIOTHERAPY TEMPLATE INSTRUCTIONS v. 5/5/2017

The protocol template is a tool to facilitate rapid protocol development. It is not intended to supersede the role of the Principal Investigator in the authoring and scientific development of the protocol. It contains the “boilerplate” language commonly required. Content may be modified as necessary to meet the scientific aims of the study and development of the protocol.

For further details and examples, please refer to the reference document located: http://cancer.case.edu/researchadmin/forms/

The BLUE text is meant to provide instructions and examples, please delete the BLUE instructions and examples and replace them with protocol specific designs.

Please refer to CCCC PRMC website for comprehensive list of definitions and examples for each protocol section. APPENDIX [record letter]

NEW YORK HEART ASSOCIATION (NYHA) CARDIAC CLASSIFICATION

The NYHA classification system relates symptoms to everyday activities and the patient’s quality of life.

Class Symptoms

No limitation of physical activity. Ordinary physical Class I (Mild) activity does not cause fatigue, palpitation, or dyspnea (shortness of breath).

Slight limitation of physical activity. Comfortable at rest, Class II (Mild) but ordinary physical activity results in fatigue, palpitation, or dyspnea.

Marked limitation of physical activity. Comfortable at Class III (Moderate) rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea.

Unable to carry out any physical activity without Class IV (Severe) discomfort. Symptoms of cardiac insufficiency at rest. If any physical activity is undertaken, discomfort is increased.

APPENDIX B

ELIGIBILITY CHECKLIST

PROTOCOL# “Protocol Name”

Research Staff will complete the eligibility checklist for the PI.

Name ______Medical Record # ______

Physician ______Study ID #______

Inclusion Criteria: ALL questions must be answered “YES” in order for a patient to be eligible. 1  Yes  No 2  Yes  No 3  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Exclusion Criteria: ALL questions must be answered “NO” in order for a patient to be eligible. 1  Yes  No 2  Yes  No 3  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No

Study Coordinator: ______Date ______

Treating Physician/ PI ______Date ______APPENDIX [record letter]

Class Symptoms

APPENDIX B

STUDY NUMBER: CASE XXXX Number willInclusion be assigned Criteria: by Cancer ALL Centerquestions at time must of be PRMC answered Submission “YES” in order for a patient to be eligible. ClinicalTrials.gov NCT #: TBD 1  Yes  No Protocol2 Date:  Yes  No 3  Yes  No STUDY4 TITLE: Full study title here (600 characters maximum)  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______PRINCIPAL INVESTIGATOR: A study can only have one Principal Investigator. Trials that are being conducted at both University Hospitals and Cleveland Clinic will list the Principal Investigator Inclusion at the Lead Criteria: Institution ALL as questions the overall must Principal be answered Investigator “YES” for thein study. order for a patient to be eligible. The Co-PI(s) refer to the physician(s) who will lead the study at non-lead institution(s). 1  Yes  No Example:2 Joint Protocol with UH Lead  Yes  No 3  Yes  No PRINCIPAL4 INVESTIGATOR: Name of Physician, MD  Yes  No Case Comprehensive Cancer Center 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______University Hospitals Cleveland Medical Center Seidman Cancer Center Inclusion Criteria: ALL11100 questions Euclid must Avenue be answered “YES” in order for a patient to beCleveland, eligible. OH 44106 1 Telephone including area code Email address  Yes  No 2  Yes  No CO-PI:3 Name of Physician, MD  Yes  No 4 Case Comprehensive Cancer Center  Yes  No Cleveland Clinic 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Taussig Cancer Center 9500 Euclid Avenue Inclusion Criteria: ALLCleveland, questions OH must 44195 be answered “YES” in order for a patient to beTelephone eligible. including area code Email address 1  Yes  No 2  Yes  No CO- INVESTIGATOR:3  Yes  No List co-investigators4 alphabetically by site in the following order:  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Case Comprehensive Cancer Center, Lead Institution, Main Site Case Comprehensive Cancer Center, Lead Institution, Regional Sites Case Comprehensive Inclusion Criteria: Cancer Center, ALL questions Non-Lead must Institution, be answered Main Site “YES” in Case Comprehensiveorder for a Cancerpatient Center,to be eligible. Non-Lead Institution, Regional Sites *If this1 is a multi-institutional study, the protocol title page should include the name of each participating institution, the investigator responsible for the study at that institution, Yes and his/her No telephone2 # and e-mail address.  Yes  No 3  Yes  No STATISTICIAN4 : Name of Statistician, degree  Yes  No Case Comprehensive Cancer Center 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Name of Institution Street Address Inclusion Criteria: ALLCity, questions State, Zip must code be answered “YES” in order for a patient to beTelephone eligible. including area code Email address 1  Yes  No STUDY2 COORDINATOR: Name of Lead Study Coordinator  Yes  No 3 Case Comprehensive Cancer Center  Yes  No 4 Name of Institution  Yes  No Street Address 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______City, State, Zip code Telephone including area code Inclusion Criteria: ALLEmail questions address must be answered “YES” in order for a patient to be eligible. SPONSOR: Case Comprehensive Cancer Center 1  Yes  No SUPPORT/FUNDING2 : List any support/grants or any funding source (partial Yes or  full) No 3 here  Yes  No 4  Yes  No SUPPLIED AGENT (S): Name of supplied agents and supplier, if applicable 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

IND #: If applicable Inclusion Criteria: ALL questions must be answered “YES” in OTHER AGENTorder for (S): a patient to beName eligible. of other agents 1  Yes  No 2  Yes  No 3  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______SUMMARY OF CHANGES

Please provideInclusion a list Criteria: of changes ALL from questions the previous must approved be answered version “YES” of the in protocol starting at IRB approval.order This for atable patient will toremain be eligible. blank until initial IRB approval. The list shall be a brief overview.1 When appropriate, a brief justification for the change should be included. This is a running list for the life of the study.  Yes  No 2  Yes  No Protocol3 Section Change  Yes  No Date 4  Yes  No Initial IRB approval 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Protocol Section Change Date

Summarize changes to first protocol amendment Inclusion Criteria: ALL questions must be answered “YES” in order for a patient to be eligible. 1  Yes  No 2  Yes  No 3  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______STUDY SCHEMA Please provide a visual schema for the study. If preferred, a summary or synopsis may be provided. Inclusion Criteria: ALL questions must be answered “YES” in order for a patient to be eligible. EXAMPLE STUDY SCHEMA - hyperlink to separate document 1  Yes  No 2  Yes  No 3  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Class Symptoms

APPENDIX B

Class Symptoms

APPENDIX B

Class Symptoms

APPENDIX B

Class Symptoms

APPENDIX B

Physician ______Study ID #______Protocol Synopsis: Please refer to PROTOCOL SUMMARY guidance document for examples Inclusion Criteria: ALL questions must be answered “YES” in PROTOCOLorder SUMMARY for a patient to be eligible. 1  Yes  No Protocol Number/Title Case CCC assigned number/Title 2 Study Phase Study phase as defined by clinicaltrials.gov  Yes  No Brief 3Background/Rationale Include:  Yes  No 4 Why doing this study on this population with this drug. Yes  No Incidence/burden 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Primary Objective Primary Endpoint(s) Inclusion Criteria: Endpoints:ALL questions how itmust will be be answeredmeasured “YES”and at what in time point. order for a patient toDo be not eligible. use “end of study” or “at progression”. Secondary Objective(s) Secondary Endpoint(s) 1  Yes  No Exploratory Objective(s) Exploratory Endpoints (s) 2 This is where exploratory research endpoints will Yesgo. For  No 3 example, gathering preliminary data  Yes  No Correlative4 Objective(s) Correlative Endpoint(s)  Yes  No This is where correlative study objectives will go. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Pharmacokinetics, Pharmacodynamics, and biomarkers, etc. Sample Size Number expected to accrue Inclusion Criteria: Age,ALL genderquestions must be answered “YES” in Disease sites/Conditionsorder for a patient toICD be terminologyeligible. Interventions1 Agent X, route, dose, cycle length, number of cycles Yes  No Agent Y, route, dose, cycle length, number of cycles 2  Yes  No 3  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______ABBREVIATIONS Please update CCCC Case Comprehensive Cancer Center table with relevant abbreviations used CRF Case Report Form in the protocol DCRU Dahm’sInclusion Clinical Criteria: Research ALL Unitquestions must be answered “YES” in DSTC Dataorder Safety for a andpatient Toxicity to be Committee eligible. FDA 1 Food and Drug Administration  Yes  No ICF 2 Informed Consent Form  Yes  No IRB 3 Institutional Review Board  Yes  No PRMC Protocol Review and Monitoring Committee 4  Yes  No SOC Standard of Care 5 CCF Cleveland Clinic Foundation  Yes  No UH 6 University Hospitals  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______TABLE OF CONTENTS

1.0 INTRODUCTIONInclusion Criteria: ALL questions must be answered “YES” in 1.1 Backgroundorder for aof patient Study Diseaseto be eligible. 1.2 1 Preclinical Data 1.3 Clinical Data to date  Yes  No 1.4 2 Rationale  Yes  No 1.5 3 Background and rationale of correlative studies  Yes  No 4  Yes  No 2.0 OBJECTIVES 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______2.1 Primary Objective 2.2 Secondary Objective(s) 2.3 ExploratoryInclusion Objective(s)Criteria: ALL questions must be answered “YES” in order for a patient to be eligible. 3.0 1 STUDY DESIGN 3.1 Study design, dose escalation, and cohorts  Yes  No 3.2 2 Number of Subjects  Yes  No 3.3 3 Replacement of Subjects  Yes  No 3.4 4 Expected Duration of Treatment and Subject Participation  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______4.0 SUBJECT SELECTION 4.1 Inclusion Criteria 4.2 ExclusionInclusion Criteria Criteria: ALL questions must be answered “YES” in 4.3 Inclusionorder for of Womena patient and to beMinorities eligible. 1 5.0 REGISTRATION  Yes  No 2  Yes  No 6.0 3 TREATMENT PLAN  Yes  No 6.1 4 Radiation Therapy  Yes  No 6.1.1 General Guidelines and Timing 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______6.1.2 Equipment and Techniques to be Used 6.1.3 Target Volumes 6.1.4Inclusion Dose Target Criteria: and OrgansALL questions at Risk Constraints must be answered “YES” in 6.2 Nameorder of forInvestigational a patient to Agentbe eligible. X Administration 6.3 1 Name of Standard of Care Agent(s) Administration 6.4 Phase I Dose Escalation  Yes  No 6.5 2 Definition of Dose Limiting Toxicity  Yes  No 6.6 3 General Concomitant Medications and Supportive Care Guidelines  Yes  No 6.7 4 Criteria for Removal from Study  Yes  No 6.8 Duration of Follow-Up 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

7.0 DOSE DELAYS / DOSE MODIFICATIONS Inclusion Criteria: ALL questions must be answered “YES” in 8.0 ADVERSEorder for EVENTSa patient toAND be eligible. POTENTIAL RISKS 8.1 1 Radiation Therapy Adverse Events 8.2 Agent X/Y Adverse events  Yes  No 8.3 2 Definitions  Yes  No 8.4 3 Serious Adverse Event Report Form  Yes  No 8.5 4 Reporting Procedures for Serious Adverse Event  Yes  No 8.6 Serious Adverse Events and OnCore® 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______8.7 Data Safety Toxicity Committee 8.8 Data and Safety Monitoring Plan Inclusion Criteria: ALL questions must be answered “YES” in 9.0 PHARMACEUTICALorder for a patient to INFORMATIONbe eligible. 9.1 1 Investigational Agent(s) 9.2 Commercial Agent(s)  Yes  No 2  Yes  No 10.0 3 CORRELATIVE/EXPLORATORY  Yes  No 10.1 4 Name of Correlative/Exploratory Study #1  Yes  No 10.2 Name of Correlative/Exploratory Study #2 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______10.3 Name of Correlative/Exploratory Study #3

11.0 STUDYInclusion PARAMETERS Criteria: ALL AND questions CALENDAR must be answered “YES” in 11.1 Studyorder Parameters for a patient to be eligible. 11.2 Calendar 1  Yes  No 12.0 2 MEASUREMENT OF EFFECT choose appropriate measurement Yes of effect;  No ie. RECIST3 (solid tumors) / hematologic diseases / other response measurement  Yes  No 4  Yes  No 13.0 RECORDS TO BE KEPT/REGULATORY CONSIDERATIONS 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______13.1 Data Reporting 13.2 Regulatory Considerations Inclusion Criteria: ALL questions must be answered “YES” in 14.0 STATISTICALorder for a patient CONSIDERATIONS to be eligible. 1 REFERENCES  Yes  No 2  Yes  No APPENDICES3  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______The investigator may choose from the following commonly used appendices and modify per protocol specifications. The investigator must supply additional appendices as needed including questionnaires Inclusion and surveys. Criteria: For ALL further questions resources, must please be answered see reference “YES” document in ____) order for a patient to be eligible. 1 APPENDIX __ ECOG / Karnofsky Performance Status Criteria  Yes  No 2  Yes  No 3 APPENDIX __  Yes  No 4 Subject Diary (pill, injectable, etc)  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______1.0 Introduction

1.1 BackgroundInclusion Criteria: ALL questions must be answered “YES” in Please provideorder background, for a patient incidence, to be eligible. and treatment information on the study disease. 1 Please be specific in the title for disease specific studies.  Yes  No 2  Yes  No Example:3 “Advanced Biliary Cancers” versus “Advanced Cancers”  Yes  No 4  Yes  No 1.2 Preclinical Data 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Provide background and brief information for agent X. Include any animal studies, the explanation of the mechanism of action, and any preclinical data about the agent or treatment. Inclusion Criteria: ALL questions must be answered “YES” in 1.3 Clinicalorder forData a patientto Date to be eligible. Summarize1 the available clinical study data with relevance to the protocol under development. If none is available, include a statement that there is no available clinical research dataYes to date  No on the investigational2 product.  Yes  No 3  Yes  No 1.4 4 Rationale  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Please provide the background and rationale for evaluating this (combination) therapy in this disease. Include the rationale for the proposed starting doses and dose escalation scheme as well as route ofInclusion administration Criteria: and dosageALL questions period. must be answered “YES” in order for a patient to be eligible. 1.5 1 Background and rationale of correlative studies Please provide the background and rationale for correlative studies and exploratory Yes endpoints.  No 2  Yes  No 2.0 3 Objectives  Yes  No Describe4 the overall objectives and purpose of the study, keeping in mind that objectives Yes must  No be measurable. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Records to be kept should capture the measurement. Study parameters (calendar) should indicate when captured. Inclusion Criteria: ALL questions must be answered “YES” in order for a patient to be eligible. 2.1 1 Primary Objective It is preferable to have only one primary objective and primary endpoint. What Yes scientific  No question2 are you trying to answer?  Yes  No 3  Yes  No Example:4 Hyperlink to examples  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______2.2 Secondary Objective(s)

Example: InclusionHyperlink Criteria: to examples ALL questions must be answered “YES” in order for a patient to be eligible. 2.3 Exploratory Objectives (s) 1  Yes  No Example:2 Hyperlink to examples  Yes  No 3.0 3 Study Design  Yes  No Please4 provide an overview of the study design and the rationale for this type of design. Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______3.1 Study design including dose escalation / cohorts This section should include: the type of trial design of the study, stages, cohort information, how subjects willInclusion be randomized Criteria: ALL and ifquestions there are must plans be toanswered use a placebo.“YES” in Please see guidance documentorder for examples for a patient of blinding/unblinding to be eligible. procedures. 1 3.2 Number of Subjects  Yes  No Provide2 the number of subjects that will be included in the study using a sentence format.Yes  No 3  Yes  No Example:4 Approximately 50 subjects will be enrolled in this trial.  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Example if more than one phase: Approximately 50 subjects will be enrolled in this trial. Approximately 15 will be enrolled in the phase I part and 35 in the phase II part. Inclusion Criteria: ALL questions must be answered “YES” in 3.3 Replacementorder for a ofpatient Subjects to be eligible. The replacement of subjects is protocol specific and needs to be tailored to the trial. 1  Yes  No Example2 : If Oral Drug is to be taken 21 out of 21 days and this is not met:  Yes  No 3  Yes  No Example4 : If a subject does not take at least 17 doses in the first cycle, the subject will Yes be replaced  No because he/she has not taken enough drug to confirm safety at that dose level. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Example: Hyperlink to further examples Inclusion Criteria: ALL questions must be answered “YES” in 3.4 Expectedorder for Duration a patient of to Treatment be eligible. and Subject Participation Please1 provide a brief summary of the length of treatment period, plus the length of follow up period and any study windows that are applicable. Please provide length of each cycle, Yes minimum  No and maximum2 number of cycles. If treatment can continue until disease progression Yes (i.e.  No no maximum3 number of cycles), please indicate here. If clinical benefit is not likely Yes until after No a certain4 number of cycles, specify that here.  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Treatment duration may be modified per section ___.

4.0 SubjectInclusion Selection Criteria: ALL questions must be answered “YES” in Each of theorder criteria for ina patientthe sections to be that eligible. follow must be met in order for a subject to be considered eligible for this study. Use the eligibility criteria to confirm a subject’s eligibility. 1  Yes  No For UH2 lead CASE Studies, please use signature lines below. For CCF lead CASE Yes studies,  No please3 remove.  Yes  No 4  Yes  No Subject’s Name ______5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Medical Record # ______Inclusion Criteria: ALL questions must be answered “YES” in Researchorder Nurse for / a patient to be eligible. Study Coordinator Signature: ______1  Yes  No Date 2______ Yes  No 3  Yes  No Treating4 Physician [Print] ______ Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Treating Physician Signature: ______

Date ______Inclusion Criteria: ALL questions must be answered “YES” in order for a patient to be eligible. Hyperlink to Inclusion/Exclusion tips and examples 1  Yes  No 4.1 2 Inclusion Criteria  Yes  No Inclusion3 Criteria must describe the subject population that you want to include Yes in the study. No Each 4statement must be able to be placed into the form of a question with a “positive” Yes response  No received. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Create a numbered list of criteria applicable to the protocol that subjects must meet to be eligible for study enrollment.Inclusion Criteria: ALL questions must be answered “YES” in order for a patient to be eligible. Subjects must meet all of the following inclusion criteria to be eligible for enrollment: 1  Yes  No Below2 are common examples: Edit per protocol or see further examples hyperlinked Yes above.  No 3  Yes  No  4 4.1.1 Subjects must have histologically or cytologically confirmed Name of Yes Disease . No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Please specify eligible disease(s)/stage(s)/prognostic score(s) as well as if staging is pathological or clinical. Inclusion Criteria: ALL questions must be answered “YES” in  4.1.2order Subjects for a patientmust have to bereceived eligible. (no, no more than X) prior therapies for this disease. **If applicable, provide guidance on what constitutes a prior line of therapy, how to count prior 1  Yes  No lines of therapy and breaks in therapy. 2  Yes  No  3 4.1.3 Age >18 years. Please state reason for age restriction.  Yes  No If applicable,4 the following text can be used;  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______“ Because no dosing or adverse event data are currently available on the use of ______in combination with ______in subjects ≤18 years of age, children are excluded from this study.” Inclusion Criteria: ALL questions must be answered “YES” in  4.1.4order Performance for a patient status to be_____ eligible. [See Appendix __]. Choose one method (not both): 1  Yes  No Example: ECOG Performance status ≤ 2 Example:2 Karnofsky Performance status ≥ 60%  Yes  No 3  Yes  No  4 4.1.5 Life expectancy of ≥ # weeks/months, in the opinion of and as documented Yes by Nothe investigator. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

 4.1.6 Subjects must have normal organ and marrow function as defined below: Add time frame if applicable.Inclusion Criteria: ALL questions must be answered “YES” in order for a patient to be eligible.  Please review for relevance to the specific study and modify. 1  Yes  No . 4.1.6.1 Hemoglobin ≥ 10.0 g/dl 2 . 4.1.6.2 Leukocytes ≥ 3,000/mcL  Yes  No 3 . 4.1.6.3 Absolute neutrophil count ≥ 1,500/mcL  Yes  No 4 . 4.1.6.4 Platelet count ≥ 100,000/mcL  Yes  No . 4.1.6.5 Total bilirubin within normal institutional limits 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______. 4.1.6.6 AST (SGOT) ≤ 2.5 X institutional upper limit of normal . 4.1.6.7 ALT (SGPT) ≤ 2.5 X institutional upper limit of normal Inclusion. Criteria:4.1.6.8 SerumALL questions creatinine mustwithin be normal answered institutional “YES” limitsin order for a patient to be eligible.  4.1.7 Please insert other appropriate eligibility criteria. 1  Yes  No 2  4.1.8 Sex (defined as a person’s classification as male or female based Yes on biological  No distinctions)3  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______ 4.1.9 Gender based (defined as self-representation of gender identity). If eligibility is based on gender, describe gender criteria. Inclusion Criteria: ALL questions must be answered “YES” in  4.1.10order Subjects for a patient must have to be the eligible. ability to understand and the willingness to sign a written informed consent document. 1  Yes  No 2 4.2 Exclusion Criteria  Yes  No Exclusion3 Criteria must describe the subject population that you do NOT want to Yes include  in Nothe study.4 Each statement must be able to be placed into the form of a question with Yes a “negative”  No response received. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Create a numbered list of criteria applicable to the protocol that would exclude a subject from study enrollment. Inclusion Criteria: ALL questions must be answered “YES” in order for a patient to be eligible. The presence1 of any of the following will exclude a subject from study enrollment. Below are common examples: Edit per protocol or see further examples hyperlinked Yes above.  No 2  Yes  No  3 4.2.1 Prior treatment toxicities resolved to ≤ Grade X according to NCI CTCAE Yes Version  No 4.0 (list4 exceptions, e.g. alopecia, neuropathy, etc).  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______ 4.2.2 Subjects receiving any other investigational agents.

 4.2.3InclusionTo be Criteria: included ALLif applicable questions to protocol. must be Suggestedanswered text“YES” is provided in below: Subjects withorder untreated for a patient brain to metastases/CNS be eligible. disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic 1  Yes  No dysfunction that would confound the evaluation of neurologic and other adverse events. 2  Yes  No  3 4.2.4 History of allergic reactions attributed to compounds of similar Yes chemical  No or biologic4 composition to Agent X or other agents used in this study.  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______ 4.2.5 Please state appropriate exclusion criteria relating to concomitant medications or substances that have the potential to affect the activity or pharmacokinetics of the study agent(s). Inclusion Criteria: ALL questions must be answered “YES” in  4.2.6orderSubjects for a patient with to uncontrolled be eligible. intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, 1  Yes  No cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study 2 requirements.  Yes  No 3  Yes  No  4 4.2.7 The investigator must state a medical or scientific reason if pregnant Yes or nursing  No subjects will be excluded from the study. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Suggested text is provided below: Pregnant Inclusionor breastfeeding Criteria: women ALL arequestions excluded must from be thisanswered study because“YES” inAgent X is Name of Agent Classorder agent for with a patient the potential to be eligible. for teratogenic or abortifacient effects. Because there is an unknown,1 but potential risk for adverse events in nursing infants secondary to treatment of the mother with Agent X, breastfeeding should be discontinued if the mother is treated Yes with Agent No X. These2 potential risks may also apply to other agents used in this study.  Yes  No 3  Yes  No  4 4.2.8 The investigator must state a medical or scientific reason if subjects Yeswho are  HIV- No positive will be excluded from the study. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Suggested text is provided below: HIV-positive Inclusion subjects Criteria: on combination ALL questions antiretroviral must be answered therapy are “YES” ineligible in because of the potential order for pharmacokinetic for a patient to interactionsbe eligible. with Agent X. In addition, these subjects are at increased1 risk of lethal infections when treated with marrow suppressive therapy. Appropriate studies will be undertaken in subjects receiving combination antiretroviral Yes therapy  when No indicated.2 Also include whether HIV testing is required for this study, or only Yes if a known No diagnosis3 will be excluded.  Yes  No 4  Yes  No  4.2.9 Insert other appropriate agent-specific exclusion criteria. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

4.3 Inclusion of Women and Minorities Make sureInclusion you include Criteria: the appropriate ALL questions verbiage must for the be subjectanswered population. “YES” in Suggestedorder text is for provided a patient below: to be eligible. 1 Men, women and members of all races and ethnic groups are eligible for this trial. Yes  No 2  Yes  No 5.0 3 Registration  Yes  No ® All subjects4 who have been consented are to be registered in the OnCore Database. Yes For  those No subjects who are consented, but not enrolled, the reason for exclusion must be recorded. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

All subjects will be registered through [Name of Lead Site] and will be provided a study number by contacting Inclusion the study Criteria: coordinator ALL listedquestions on the must cover be page. answered “YES” in order for a patient to be eligible. Include if a registration form will be required. 1  Yes  No If the 2trial is randomized the method of randomization should be stated as well as Yesthe proportion  No of subjects3 that will be accrued to each dose level.  Yes  No Example4 : Subjects will be randomized equally to the four dose levels being Yes studied  using No permuted blocks. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

6.0 Treatment Plan Briefly describeInclusion the Criteria:treatment ALLregimen questions planned. must If there be answered are different “YES” cohorts, in label each cohort and appropriateorder treatmentfor a patient schedule: to be eligible.  Pre-medications allowed/required/suggested (if applicable) 1  Yes  No  Agent(s) (if applicable) 2  Dose(s) (of agents and RT)  Yes  No  3 Route of administration  Yes  No  4 Treatment schedule (including pre-treatment prep)  Yes  No  5 Treatment duration  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Please provide separate regimen descriptions for different treatment groups of subjects as necessary. Inclusion Criteria: ALL questions must be answered “YES” in order for a patient to be eligible. The investigator1 must include the following statement if treatment is required to be administered only on an inpatient basis: Treatment must be administered only on an inpatient basis. Yes  No 2  Yes  No 6.1 3 Radiation Therapy  Yes  No 6.1.1 4General Guidelines and Timing  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Describe the general rationale for radiation therapy and indications. Describe how radiation will be scheduled relative to chemotherapy administration if applicable. Inclusion Criteria: ALL questions must be answered “YES” in 6.1.2 Equipmentorder for and a Techniquespatient to be to eligible.be used Provide1 details of treatment machine(s) (linear accelerator, proton beam, cyberknife, gamma knife) and techniques to be utilized (IMRT, TBI, SBRT, 3D CRT, etc). Describe immobilization, Yes  No simulation,2 motion management approach, image fusion, and other techniques.  Yes  No 3  Yes  No 6.1.3 4Target Volumes  Yes  No Provide details on GTV, CTV and PTV and/or other target description as applicable. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

6.1.4 Dose to Target and Organs at Risk Constraints Provide detailsInclusion on prescribed Criteria: dose ALL and questions fractionation. must be Include answered prescription “YES” points, in coverage goals and dose limitsorder onfor OARs. a patient to be eligible. 1 6.2 Name of Investigational Agent X Administration (If applicable, for Yesstudies  using No investigational2 chemotherapy agents or investigational agent combinations) Yes  No In addition3 to a dosing schema, please add a narrative description of the investigational Yes  agent No administration.4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Investigational Agent Administration Example : Subjects willInclusion receive Criteria: Agent X ALL ___ mg/m2questions on mustDays be1-3 answered of each (28 “YES” day) cycle.in Name of Agent will be administeredorder for a IV patient over 2 to hours. be eligible. 1 Example:  Yes  No Subjects2 will receive Agent Y ___ mg/m2 by IV on Day 1 of each 21-day cycle. Yes Prior to  each No Name3 of Agent treatment, pre-hydrate with at least 1000 ml normal saline and use Yes diuretics  Noper institutional4 guidelines.  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Example : Subjects will receive Agent Z ____mg/m2 by IV on days 1, 2, and 3 of each 21-day cycle. Inclusion Criteria: ALL questions must be answered “YES” in Please addorder subsequent for a patient sections to for be additional eligible. investigational agents or agent combinations. 6.3 1 Name of Standard of Care Agent(s) Administration (If applicable, for studies using Standard of Care chemotherapy agents or standard of care agent combinations) Yes  No In addition2 to a dosing schema, please add a narrative description of the non-investigational Yes  No agent 3administration in the same format as above.  Yes  No 4  Yes  No SOC 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Example : Subjects will receive Agent X ___ mg/m2 on Days 1-3 of each (28 day) cycle. Agent X will be administered Inclusion IV over Criteria: 2 hours. ALL questions must be answered “YES” in order for a patient to be eligible. Example1 : Subjects will receive Agent Y ___ mg/m2 by IV on Day 1 of each 21-day cycle. Yes Prior to  each No Agent2 Y treatment, pre-hydrate with at least 1000 ml normal saline and use Yes diuretics  Noper institutional3 guidelines.  Yes  No 4  Yes  No Example: 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Subjects will receive Agent Z ___ mg/m2 by IV on days 1, 2, and 3 of each 21-day cycle.

6.4 PhaseInclusion I Dose Criteria: Escalation ALL (if questionsapplicable) must be answered “YES” in Dose escalationorder forwill a proceed patient within to be eligible.each cohort according to the following scheme. Dose- limiting toxicity (DLT) is defined in section 6.5. 1  Yes  No 2  Yes  No Number of Subjects with DLT 3 Escalation Decision Rule  Yes  No at a Given Dose Level 4  Yes  No 0 out of 3 Enter 3 subjects at the next dose level. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______1 out of 3 Enter at least 3 more subjects at this dose level.  If 0 of these 3 subjects experience DLT, Inclusion Criteria: ALL questions must be answered “YES” in proceed to the next dose level. order for a patient to be eligible. 1  If 1 or more of this group suffer DLT, then Yes  No 2 dose escalation is stopped, and this dose Yes is  No 3 declared the maximally administered dose. Yes  No Three (3) additional subjects will be entered 4  Yes  No at the next lowest dose level if only 3 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______subjects were treated previously at that dose. >2 Dose escalation will be stopped. This dose level Inclusion Criteria: ALL questions must be answered “YES” in will be declared the maximally administered dose order for a patient to be eligible. (highest dose administered). Three (3) additional 1  Yes  No subjects will be entered at the next lowest dose 2  Yes  No level if only 3 subjects were treated previously at 3  Yes  No that dose. 4  Yes  No <1 out of 6 at highest dose level This is generally the recommended phase 2 dose. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______below the maximally At least 6 subjects must be entered at the administered dose recommended phase 2 dose. Inclusion Criteria: ALL questions must be answered “YES” in order for a patient to be eligible. 1  Yes  No 6.5 2 Definition of Dose-Limiting Toxicity (Applicable for dose escalation studies Yes only)  No Dose limiting toxicities must be suspected to be related to the investigational product (please 3  Yes  No refer to section __ for all other dose modifications). For dose escalation studies, please provide explicit4 definitions of the type(s), grade(s), and duration(s) of adverse events Yes that will  No be 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______considered dose-limiting toxicity(s), or provide definitions of other endpoints that will be used to determine dose escalations. Inclusion Criteria: ALL questions must be answered “YES” in Managementorder and for dose a patient modifications to be eligible. are outlined in Section 7. 1 6.6 General Concomitant Medications and Supportive Care Guidelines  Yes  No State 2guidelines for use of which concomitant medicines/therapies are permitted Yes during  Nothe study,3 and which concomitant medicines/therapies are not permitted during Yes the study  No (if applicable).4 Include any additional rescue therapies or supportive care medications Yes or treatments  No required for administration of each agent in the treatment. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Suggestive text, as applicable for supportive care: Subjects should receive full supportive care, including Inclusion transfusions Criteria: of ALL blood questions and blood must products, be answered cytokines, “YES” antibiotics, in antiemetics, etc when appropriate.order for a patient to be eligible. 1 Example:  Yes  No Because2 there is a potential for interaction of Name of Agent(s) with other Yesconcomitantly  No administered3 drugs through the cytochrome P450 system, the case report form must Yes capture  Nothe concurrent4 use of all other drugs, over-the-counter medications, or alternative Yestherapies.  TheNo Principal Investigator should be alerted if the subject is taking any agent known to affect or with 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______the potential to affect selected CYP450 isoenzymes. Please refer to Appendix _____ for a complete list. Inclusion Criteria: ALL questions must be answered “YES” in 6.7 Criteriaorder forfor aRemoval patient tofrom be eligible.Study In the1 absence of treatment delays due to adverse events, treatment may continue for # cycles or until one of the following criteria applies:  Yes  No 2  Yes  No • Disease3 progression,  Yes  No 4  Yes  No • Intercurrent illness that prevents further administration of treatment, 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

• The investigator considers it, for safety reasons, to be in the best interest of the subject. Inclusion Criteria: ALL questions must be answered “YES” in • Unacceptableorder adverse for a patient event(s) to [bebe eligible.specific] 1 Example : Unacceptable treatment related toxicity, NCI CTC AE version 4.0 Grade Yes 3 or  4 thatNo fails to2 recover to baseline or < Grade 3 in the absence of treatment within 4 weeks Yes  No 3  Yes  No Example4 : Any toxicity or other issue that causes a delay of study drug administration Yes by  more No than 4 weeks 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

• General or specific changes in the subject’s condition render the subject unacceptable for further treatmentInclusion in theCriteria: judgment ALL of questionsthe investigator, must be answered “YES” in order for a patient to be eligible. • Subject decision to withdraw from treatment (partial consent) or from the study (full consent), 1  Yes  No • Pregnancy2 during the course of the study for a child-bearing participant  Yes  No 3  Yes  No • Death,4 or  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______• Sponsor reserves the right to temporarily suspend or prematurely discontinue this study. The date and reason for discontinuation must be documented. Every effort should be made to complete Inclusionthe appropriate Criteria: assessments. ALL questions must be answered “YES” in order for a patient to be eligible. 6.8 1 Duration of Follow Up Investigators must be sure to match the duration of follow-up with the calendar Yes regardless  No if survival2 is the endpoint of a study. Please indicate here if the sponsor-investigator Yes intents  No to capture3 information after a patient withdraws from study (per patient agreement). Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Subjects will be followed for toxicity for 30 days (minimum suggested time frame, follow up time frame should be appropriate to the metabolism of the product) after treatment has been discontinued Inclusion or until Criteria: death, whichever ALL questions occurs first. must be answered “YES” in order for a patient to be eligible. The clinical1 course of each event will be followed until resolution, stabilization, or until it has been determined that the study treatment or participation is not the cause. [The investigator Yes  may No want to2 consider a cut off of 6 months.]  Yes  No 3  Yes  No Serious4 adverse events that are still ongoing at the end of the study period will Yes necessitate  No follow-up to determine the final outcome. Any serious adverse event that occurs after the study 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______period and is considered to be possibly related to the study treatment or study participation will be recorded and reported immediately. Inclusion Criteria: ALL questions must be answered “YES” in 7.0 Dosingorder Delays/Dose for a patient Modifications to be eligible. Treatment1 modifications/dosing delays and the factors predicating treatment modification should be explicit and clear. If dose modifications or radiation treatment delays are anticipated, Yes please No provide2 a dose de-escalation schema. If you plan to allow dose re-escalation Yesfor 1 or  more No agents,3 please specify dose re-escalation process in this section.  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______All treatment modifications must be expressed as a specific dose or amount rather than as a percentage of the starting or previous dose. Inclusion Criteria: ALL questions must be answered “YES” in Please considerorder dosingfor a patient formulation to be wheneligible. calculating dose modifications for ORAL agents. 1 Dose modifications/treatment delays may be presented separately or together as appropriate. Yes  No 2  Yes  No Please3 see examples of dosing delays and modifications in the guidance document. Yes  No 4  Yes  No 8.0 Adverse Events and Potential Risks 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

8.1 Radiation Therapy For RT, pleaseInclusion include Criteria: a comprehensive ALL questions list mustof all be reported answered adverse “YES” events in and any potential risks. order for a patient to be eligible. 1 8.2 Agent X/Y  Yes  No For treatment2 agents, please include a comprehensive list of all reported adverse eventsYes and  anyNo potential3 risks for each agent (such as the toxicities seen with another agent of the Yes same class  No or risks seen4 in animals administered this agent) as provided by the manufacturer/CAEPR. Yes Please No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______also include the recommended treatment for the commonly occurring events. This information may be provided in tabular format. Inclusion Criteria: ALL questions must be answered “YES” in For a commercialorder for agent, a patient please to provide be eligible. a list of those adverse events most likely to occur on this study,1 and refer the reader to the package insert(s) for the comprehensive list of adverse events. Please also include the recommended clinical management for the commonly occurring Yes events.  No 2  Yes  No This information3 may be provided in tabular format.  Yes  No 4  Yes  No 8.3 Definitions 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

8.3.1 Adverse Event An adverse Inclusion event Criteria: (AE) is any ALL unfavorable questions mustor unintended be answered event, “YES” physical in or psychological, associatedorder with afor research a patient study, to be which eligible. causes harm or injury to a research participant as a result of the1 participant’s involvement in a research study. The event can include abnormal laboratory findings, symptoms, or disease associated with the research study. The event does notYes necessarily  No have 2to have a causal relationship with the research, any risk associated with the Yes research,  Nothe research3 intervention, or the research assessments.  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Adverse events may be the result of the interventions and interactions used in the research; the collection of identifiable private information in the research; an underlying disease, disorder, or condition Inclusionof the subject; Criteria: and/or ALL other questions circumstances must beunrelated answered to the “YES” research in or any underlying disease, disorder,order for or acondition patient toof bethe eligible. subject. 1  Yes  No 8.3.2 Serious Adverse Events 2 Yes No A serious adverse event (SAE) is any adverse experience occurring at any dose that results in 3 any of the following outcomes:  Yes  No  4 Results in death.  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______ Is a life-threatening adverse experience. The term life-threatening in the definition of serious refers to an adverse event in which the subject was at risk of death at the time of theInclusion event. It Criteria: does not ALLrefer toquestions an adverse must event be answeredwhich hypothetically “YES” in might have caused deathorder if it for were a patient more severe. to be eligible.  1 Requires inpatient hospitalization or prolongation of existing hospitalization Yes . Any No adverse event leading to hospitalization or prolongation of hospitalization will be 2  Yes  No considered as Serious, UNLESS at least one of the following expectations is met: 3 o The admission results in a hospital stay of less than 24 hours OR Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______o The admission is pre-planned (e.g., elective or scheduled surgery arranged prior to the start of the study) OR Inclusiono The Criteria: admission ALL questions is not associated must be answered with an “YES” adverse in event (e.g., social order forhospitalization a patient to be for eligible. purposes of respite care. 1 However it should be noted that invasive treatment during any hospitalization Yes may  fulfill No the criteria of “medically important” and as such may be reportable as a serious adverse 2  Yes  No event dependant on clinical judgment. In addition where local regulatory authorities 3 specifically require a more stringent definition, the local regulation takes precedent. Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______ Results in persistent or significant disability/incapacity. The definition of disability is a substantial disruption of a person’s ability to conduct normal life’s functions.  Is Inclusiona congenital Criteria: anomaly/birth ALL questions defect. must be answered “YES” in  Is orderan important for a patient medical to be event eligible.. Important medical events that may not result death, be 1 life-threatening, or require hospitalization may be considered a serious Yes adverse  No experience when, based upon appropriate medical judgment, they may jeopardize the 2  Yes  No subject and may require medical or surgical intervention to prevent one of the outcomes 3 listed in this definition. Examples of such medical events include allergic Yesbronchospasm  No 4 requiring intensive treatment in an emergency room or at home,  blood Yes disease  No or 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______disorders, or convulsions that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse. The development of a new cancer is alwaysInclusion considered Criteria: an important ALL questions medical must event. be answered “YES” in order for a patient to be eligible. Investigators may choose to include exclusions to Serious Adverse Events being reported. 1  Yes  No Example: For the purpose of this study the following events would not be considered adverse 2 events and would not be recorded in the database:  Yes  No 3  Abnormal laboratory findings considered associated to the original disease Yes  No 4  Yes  No 8.3.3 Adverse Event Evaluation 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______The investigator or designee is responsible for ensuring that all adverse events (both serious and non-serious) observed by the clinical team or reported by the subject which occur after the subject hasInclusion signed theCriteria: informed ALL consent questions are mustfully berecorded answered in the “YES” subject’s in medical records. Source documentationorder for a patient must be to available be eligible. to support all adverse events. 1 A laboratory test abnormality considered clinically relevant (e.g., causing theYes subject  No to withdraw2 from the study, requiring treatment or causing apparent clinical manifestations, Yes  result No in a delay3 or dose modification of study treatment, or judged relevant by the investigator Yes ), should No be reported4 as an adverse event.  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______The investigator or sub-investigator (treating physician if applicable) will provide the following for all adverse events (both serious and non-serious):  EventInclusion term (as Criteria: per CTCAE) ALL questions must be answered “YES” in  Descriptionorder for ofa patientthe event to be eligible.  1 Date of onset and resolution  Yes  No  Expectedness of the toxicity 2  Yes  No  Grade of toxicity 3  Attribution of relatedness to the investigational therapy/agent- (this Yes must  No be 4 assigned by an investigator, sub-investigator, or treating physician)  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______ Action taken as a result of the event, including but not limited to; no changes, dose interrupted, reduced, discontinued, etc. or action taken with regard to the event, i.e. no action,Inclusion received Criteria: conmed ALL or other questions intervention, must be etc. answered “YES” in  Outcomeorder for of eventa patient to be eligible. 1  Yes  No Descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse 2 Events (CTCAE) version X will be utilized for agent AE reporting.  Yes  No 3  Yes  No An expected4 adverse event is an event previously known or anticipated toYes result  from No participation in the research study or any underlying disease, disorder, or condition of the 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______subject. The event is usually listed in the Investigator Brochure, consent form or research protocol. Inclusion Criteria: ALL questions must be answered “YES” in An unexpectedorder foradverse a patient event to is be an eligible. adverse event not previously known or anticipated to result from the research study or any underlying disease, disorder, or condition of the subject. 1  Yes  No Attribution2 is the relationship between an adverse event or serious adverse event Yes and the  study No drug. 3 Attribution will be assigned as follows:  Yes  No 4  Yes  No  Definite – The AE is clearly related to the study drug. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______ Probable – The AE is likely related to the study drug.  Possible – The AE may be related to the study drug.  InclusionUnlikely Criteria:– The AE ALLis doubtfully questions related must to be the answered study drug. “YES” in  orderUnrelated for a –patient The AE to is be clearly eligible. NOT related to the study drug. 1  Yes  No Protocol2 must specify if attribution is required for individual components of the treatment regimen or the treatment regimen as a whole.  Yes  No 3  Yes  No 8.4 4 SAE Report Form  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______SAE’s related to radiation therapy only will be recorded into OnCore and reported to IRB according to local IRB policies and procedures. Inclusion Criteria: ALL questions must be answered “YES” in SAEs relatedorder to foragent a patienttherapy towill be be eligible. recorded on the FDA Form 3500A (MedWatch) but should only be1 reported as instructed below. The electronic FDA SAE reporting forms should not be used.  Yes  No 2  Yes  No 8.5 3 Reporting Procedures for Serious Adverse Events  Yes  No For the4 purposes of safety reporting, all adverse events will be reported that occur Yes [Please  insert No appropriate time frame, e.g. on or following first day of RT, on day of registration, etc.] through 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______30 days after the final dose of study radiation therapy/drug. Adverse events, both serious and non-serious, and deaths that occur during this period will be recorded in the source documents. All SAEs Inclusion should be Criteria: monitored ALL until questions they are resolvedmust be oranswered are clearly “YES” determined in to be due to a subject’s orderstable foror chronica patient condition to be eligible. or intercurrent illness(es). Related AEs will be followed until resolution to baseline or grade 1 or stabilization. 1  Yes  No 8.5.1 2 SAE Reporting Requirements  Yes  No  3 Participating investigators (all sites) must report all serious adverse events Yes to the  Lead No 4 Site Principal Investigator (e.g. Sponsor-Investigator) within 24 hours of Yes discovery  No or 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______notification of the event. The participating investigator must also provide follow-up information on the SAE until final resolution. Inclusiono Insert Criteria: Lead Site ALL PI’s email/faxquestions number must be (as answered applicable). “YES” Protocol in coordinator can orderbe for contacted a patient if toapplicable. be eligible.  1 The Lead Site Principal Investigator will review the SAE and report the Yes event to Nothe FDA, external collaborator(s), and IRB as applicable. 2  It is the Sponsor-Investigator’s responsibility (e.g. lead site PI) to ensure Yes that  ALL No 3 serious adverse events that occur on the study (e.g. ALL SAEs that Yes occur at  each No 4 enrolling institution) are reported to all participating sites.  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Drug Supplier / Manufacturer / Financial Supporter Reporting Requirements:  Insert the external entity’s reporting Requirements. Please include language that specifies theInclusion Sponsor-Investigator Criteria: ALL (e.g. questions lead site PI)must will be be answered responsible “YES” for reporting in all SAEs to theorder external for entity.a patient to be eligible. 1  Yes  No Institutional Review Board Reporting Requirements: 2  Investigative sites will report adverse events to their respective IRB according Yes to the  local No 3 IRB’s policies and procedures in reporting adverse events.  Yes  No 4  Yes  No 8.6 SAEs and OnCore 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______ All SAEs will be entered into OnCore.  A copy of the SAE form(s) submitted to the sponsor-investigator is also uploaded into Oncore.Inclusion Criteria: ALL questions must be answered “YES” in order for a patient to be eligible. 1 8.7 Data Safety and Toxicity Committee  Yes  No It is the2 responsibility of each site PI to ensure that ALL SAEs occurring on this trial Yes (internal  No or external)3 are reported to the Case Comprehensive Cancer Center’s Data and Safety Yes Toxicity  No Committee.4 This submission is simultaneous with their submission to the sponsor Yes and/or  other No regulatory bodies 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

The sponsor-investigator is responsible for submitting an annual report to the DSTC as per CCCC DataInclusion and Safety Criteria: Monitoring ALL Plan.questions must be answered “YES” in order for a patient to be eligible. 8.8 1 Data and Safety Monitoring Plan This protocol will adhere to the policies of the Case Comprehensive Cancer Center Yes Data and  No Safety2 Monitoring Plan in accordance with NCI guidelines.  Yes  No 3  Yes  No 9.0 4 PHARMACEUTICAL INFORMATION  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______A list of the adverse events and potential risks associated with the investigational or commercial agents administered in this study can be found in Section #. If applicable. Inclusion Criteria: ALL questions must be answered “YES” in Pharmaceuticalorder informationfor a patient must to be be eligible. tailored to the specific protocol. Repeat this section for all pharmaceutical1 agents being given. If protocol does not include any investigational agents and is RT only, add RT risks in section 9.1.  Yes  No 2  Yes  No The pharmaceutical3 section must contain at least the following information, available Yes from  Nothe appropriate4 Investigator’s Brochure or package insert:  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______9.1 Investigational Agents 9.1.1 Name of Agent ______Inclusion Criteria: ALL questions must be answered “YES” in Otherorder Names: for a patient ______to be eligible. 1 Product description: (e.g. doses, tablets, vials, powder, etc…- if capsules of varying Yes doses  Noare supplied2 these should be described)  Yes  No 3  Yes  No Packaging:4 (e.g. hard gelatin capsules in bottles, capsule s in blister packs, vials, etc…) Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Solution preparation: (how the agent is to be prepared): Describe in detail all the steps necessary to properly prepare agent. Include reconstitution directions and directions for further dilution, ifInclusion appropriate. Criteria: ALL questions must be answered “YES” in Storage requirements:order for a patient Include to thebe eligible.requirements for the original agent form, reconstituted solution, and final diluted product, as applicable. 1  Yes  No Stability:2 Include the stability of the original agent form, reconstituted solution, and Yes final diluted No product,3 as applicable.  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Route of administration: Include a description of the method to be used and the rate of administration, if applicable. Inclusion Criteria: ALL questions must be answered “YES” in Example :order continuous for a patient intravenous to be infusion eligible. over 24 hours, short intravenous infusion over 30-60 minutes, intravenous bolus, etc. Describe any precautions required for safe administration. 1  Yes  No Drug 2Procurement: Investigational drug may or may not be supplied for a study. YesPlease be  sure No to make3 this clear by inserting one of the statements below as applicable:  Yes  No 4  Yes  No Manufacturer (must specify if the Sponsor-Investigator developed the agent) 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

When drug is not supplied: Agent X must be obtained from commercial sources. Inclusion Criteria: ALL questions must be answered “YES” in Example :order Agent for X a must patient be obtainedto be eligible. from commercial sources and is available in 500 mg/10 ampules1 and vials, and 1 gm/20 ml, 2.5 gm/50 ml, and 5 gm/100 ml vials. Consider including the following statement while reviewing the template: The cost of this agent will be Yes the subject’s  No responsibility.2  Yes  No 3  Yes  No When4 drug is supplied: Study Agent X will be supplied for this study by Sponsor/company Yes  No name. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Packaging and labeling: Must specify the contents of the label if the Sponsor-Investigator developed Inclusion the agent: Criteria: name of ALLdrug, questions quantity ofmust drug, be date answered of packaging, “YES” recommendedin storage temp, lot number)order for a patient to be eligible. 1 Drug Accountability: To be included when drug is supplied  Yes  No The investigator2 or designated study personnel are responsible for maintaining Yes accurate  No dispensing3 records of the study drug. All study drugs must be accounted for, including Yes  study No drug accidentally4 or deliberately destroyed. Under no circumstances will the investigator Yes  allow No the investigational drug to be used other than as directed by the protocol. If appropriate, drug 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______storage, drug dispensing, and drug accountability may be delegated to the pharmacy section of the investigative site. Inclusion Criteria: ALL questions must be answered “YES” in Drug Destructionorder for : Toa patient be included to be wheneligible. drug is supplied This section1 should note the procedures for final reconciliation of the site’s drug or device supply at the end of the study, and whether study drug or device is to be shipped back Yesto a source  No or destroyed2 on site. If drug or device is to be shipped back to a source, note the address Yes and contact  No information3 here.  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Suggested language: “At the completion of the study, there will be a final reconciliation of drug shipped, drug consumed, and drug remaining. This reconciliation will be logged on the drug reconciliation Inclusion form, Criteria: signed and ALL dated. questions Any discrepancies must be answered noted will“YES” be investigated,in resolved, and documentedorder for prior a patient to return to orbe destruction eligible. of unused study drug. Drug destroyed on site will be documented in the study files.” 1  Yes  No Other2 Information : Include any other information, e.g., any special handling, Yes any nursing  No implications,3 and any subject care implications.  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Note: if the protocol involves a placebo the sections listed above apply to all components of the protocol’s treatment regimen (including placebo – if applicable) Inclusion Criteria: ALL questions must be answered “YES” in 9.2 Commercialorder for a Agent patient to be eligible. 9.2.1 Name of Agent ______1  Yes  No 2 Other Names: ______ Yes  No 3  Yes  No Product4 description: (e.g. doses, tablets, vials, powder, etc…- if capsules of varying Yes doses  Noare supplied these should be described) 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Solution preparation: (how the agent is to be prepared): Describe in detail all the steps necessary Inclusion to properly Criteria: prepare ALLagent. questions Include reconstitution must be answered directions “YES” and in directions for further dilution, iforder appropriate. for a patient to be eligible. 1 Storage requirements: Include the requirements for the original agent form, reconstituted Yes  No solution,2 and final diluted product, as applicable.  Yes  No 3  Yes  No Stability:4 Include the stability of the original agent form, reconstituted solution, and Yes final diluted No product, as applicable. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Route of administration: Include a description of the method to be used and the rate of administration, Inclusion if applicable. Criteria: ALL questions must be answered “YES” in order for a patient to be eligible. Example1 : continuous intravenous infusion over 24 hours, short intravenous infusion over 30-60 minutes, intravenous bolus, etc. Describe any precautions required for safe administration. Yes  No 2  Yes  No Drug 3Procurement: Investigational drug may or may not be supplied for a study. YesPlease be  sure No to make4 this clear by inserting one of the statements below as applicable:  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Manufacture (must specify if the Sponsor-Investigator developed the agent)

When drugInclusion is not supplied Criteria:: Agent ALL X questionsmust be obtained must be from answered commercial “YES” sources. in order for a patient to be eligible. Example:1 Agent X must be obtained from commercial sources and is available in 500 mg/10 ampules and vials, and 1 gm/20 ml, 2.5 gm/50 ml, and 5 gm/100 ml vials. Consider Yes including  Nothe following2 statement while reviewing the template: The cost of this agent will be Yes the subject’s  No responsibility.3  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______When drug is supplied: Study Agent X will be supplied for this study by Sponsor/company name. Inclusion Criteria: ALL questions must be answered “YES” in Packagingorder and for labeling a patient: Must to be specify eligible. the contents of the label if the Sponsor-Investigator developed1 the agent: name of drug, quantity of drug, date of packaging, recommended storage temp, lot number)  Yes  No 2  Yes  No Drug 3Accountability: To be included when drug is supplied  Yes  No The investigator4 or designated study personnel are responsible for maintaining Yes accurate  No dispensing records of the study drug. All study drugs must be accounted for, including study 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______drug accidentally or deliberately destroyed. Under no circumstances will the investigator allow the investigational drug to be used other than as directed by the protocol. If appropriate, drug storage, drugInclusion dispensing, Criteria: and ALLdrug accountabilityquestions must may be answeredbe delegated “YES” to the in pharmacy section of the investigativeorder for site. a patient to be eligible. 1 Drug Destruction : To be included when drug is supplied  Yes  No This section2 should note the procedures for final reconciliation of the site’s drug or Yes device supply No at the3 end of the study, and whether study drug or device is to be shipped back Yesto a source  No or destroyed4 on site. If drug or device is to be shipped back to a source, note the address Yes and contact  No information here. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Suggested language: “At the completion of the study, there will be a final reconciliation of drug shipped, drugInclusion consumed, Criteria: and ALL drug questionsremaining. must This be reconciliation answered “YES” will be in logged on the drug reconciliationorder form, for a signed patient and to bedated. eligible. Any discrepancies noted will be investigated, resolved, and documented1 prior to return or destruction of unused study drug. Drug destroyed on site will be documented in the study files.”  Yes  No 2  Yes  No Other3 Information : Include any other information, e.g., any special handling, Yes any nursing  No implications,4 and any subject care implications.  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Note: if the protocol involves a placebo the sections listed above apply to all components of the protocol’s treatment regimen (including placebo – if applicable) Inclusion Criteria: ALL questions must be answered “YES” in 10.0 CORRELATIVEorder for a patient STUDIES to be eligible. If this1 trial does not include correlative or special studies, this section should be marked “N/A” and all instructions as well as the text below deleted.  Yes  No 2  Yes  No This section3 should be developed in close collaboration with the Translational Yes Research  andNo Pharmacology4 Core (TRPC) personnel at an early stage in protocol development. YesPlease refer  No to guidance document for instructions. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

10.1 Name of Correlative study #1 Describe theInclusion endpoint Criteria: of correlative ALL questionsanalysis #1. must be answered “YES” in order for a patient to be eligible. 10.1.11 Background Provide background describing the scientific basis for the correlative endpoint and Yes its relevance  No to the2 objectives of the study.  Yes  No 3  Yes  No 10.1.24 Rationale for Analysis  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Describe how the analytical data will be analyzed and advance the objectives of the study. Consultation with Biostatistics is recommended for this section. Inclusion Criteria: ALL questions must be answered “YES” in 10.1.3 Collectionorder for of a Specimens patient to be eligible. Include1 the number and specific type of specimens to be acquired from each subject, timepoints (cycles, day) and at what time. This information should also be included in the Study Yes Calendar.  No You may2 also create a table that is correlative study procedure specific and add to thisYes section.  No 3  Yes  No Please4 see Correlative study guidance document for exploratory study calendar examples. Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______10.1.4 Handling of Specimens Describe critical aspects of all processes involved in proper handling of the specimens. Include namesInclusion and Criteria: contact ALL information questions (address, must be phoneanswered number, “YES” email, in pager, etc.) of laboratoriesorder and/or for individualsa patient to responsible be eligible. for the acquisition, transportation, storage, tracking, processing,1 shipping and analyses of all specimens. Also include specific requirements for the handling of the specimens, including transport media, temperature, type of storage Yes vessels No (including2 type and volume of blood draw tubes, (e.g. heparin, EDTA, purple top, Yes red top  etc.), No and maximal3 allowable time to complete processing or freezing.  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Please detail how the samples need to be shipped, when they need to be shipped, when to notify the lab of incoming shipment and any additional time restrictions. 10.1.5 AnalyticalInclusion Laboratory Criteria: ALL questions must be answered “YES” in Will the specimensorder for a be patient analyzed to be at eligible. a clinical laboratory, a central reference laboratory, other collaborating1 laboratory, a Case Comprehensive Cancer Center Core Laboratory, or the Principal Investigator’s laboratory? Please provide all contact information including the responsible Yes party. No 2  Yes  No 10.1.63 Methods  Yes  No Describe4 the methods used to measure the endpoint. Provide references or general Yesinformation  No on the assay. Please state if a clinically validated assay (CLIA or CAP approved) will be used. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

In the event that there are more than one correlative/exploratory studies: Please repeat sections asInclusion follows, Criteria:numbering ALL appropriately: questions must Instructions be answered same “YES” as above. in order for a patient to be eligible. 10.2.1 Background 1  Yes  No 10.2.22 Rationale for Analysis  Yes  No 3  Yes  No 10.2.34 Collection of Specimens  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______10.2.4 Handling of Specimens

10.2.5 AnalyticalInclusion Laboratory Criteria: ALL questions must be answered “YES” in order for a patient to be eligible. 10.2.6 Methods 1  Yes  No 11.0 2 STUDY PARAMETERS AND CALENDAR  Yes  No Be aware3 of criteria prone to deviations.  Yes  No 4  Yes  No 11.1 Study Parameters 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Study parameters are used in conjunction with the study calendar. Please include these common criteria in study parameters: procedures that are not standard of care or are research procedures only, any Inclusion extra labs Criteria: or imaging ALL studies questions that maymust need be answered to be performed, “YES” inany demographics or quality of orderlife questionnaires for a patient that to be may eligible. be completed, all correlative study instructions. 1 11.1.1 Screening Evaluation  Yes  No Provide2 any necessary information that is not captured by the procedures in the Yesstudy calendar  No here. Please3 see guidance document for specific examples.  Yes  No 4  Yes  No Please include any pre-RT planning in this section. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

11.1.2 Treatment Period Provide anyInclusion necessary Criteria: information ALL questionsabout each must cycle/treatment be answered visit “YES” that isin not captured in the study calendarorder for here. a patient Please to note be ifeligible. any procedures need to be completed within a certain timeframe.1 Be sure to include windows for fiducial placement, labs, visits, imaging, etc in order to avoid having to repeat tests, etc; e.g., labs +/- 3 days.  Yes  No 2  Yes  No 3  Yes  No 11.2 4 Calendar  Yes  No Please thoroughly review calendar guidance document. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Consider a window of days, if appropriate for study. Indicate which components of the trial are appropriate Inclusion for the Criteria:window. ALL The investigatorquestions must should be answeredbe cautious “YES” of tight in windows (e.g., 24 hours) whichorder may for a lead patient to manyto be eligible. needless repeat tests or deviations and are almost never necessary. 1  Yes  No Examples2 :  Yes  No A visit3 window of +/- 3 days is allowed for labs (be specific: hematology and/or chemistries). Yes  No A visit4 window of +/- 1 day is allowed for treatment.  Yes  No A visit window of +/- 7 days is allowed for 3 month follow-up visits. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

12.0 MEASUREMENT OF EFFECT Please provideInclusion response Criteria: criteria. ALL If the questions criteria formust solid be tumorsanswered in the “YES” guidance in document are not applicable,order the investigator(s)for a patient to should be eligible. provide agent – or disease-appropriate criteria (e.g., for specific hematologic malignancies, supportive care agents, etc) with references. 1  Yes  No 13.0 2 DATA REPORTING / REGULATORY CONSIDERATIONS  Yes  No 3  Yes  No Adverse4 event lists, guidelines, and instructions for AE reporting can be found Yesin Section  No8.0 (Adverse Events: List and Reporting Requirements). 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

13.1 Data Reporting ® The OnCore Inclusion Database Criteria: will be ALL utilized, questions as required must bybe theanswered Case Comprehensive “YES” in Cancer Center, ® to provideorder data for collection a patient for to bothbe eligible. accrual entry and trial data management. OnCore is a Clinical Trials Management System housed on secure servers maintained at Case Western 1 Yes No Reserve University. OnCore®. Access to data through OnCore® is restricted by user accounts and assigned2 roles. Once logged into the OnCore® system with a user ID and password, Yes OnCore  No® defines3 roles for each user which limits access to appropriate data. User information Yes  andNo ® password4 can be obtained by contacting the OnCore Administrator Yes at OnCore-  No [email protected]. 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

® OnCore is designed with the capability for study setup, activation, tracking, reporting, data monitoring Inclusion and review, Criteria: and eligibility ALL questions verification. must This be answeredstudy will “YES”utilize electronicin Case Report ® Form completionorder for in athe patient OnCore to be database. eligible. A calendar of events and required forms are available in OnCore®. 1  Yes  No 13.2 2 Regulatory Considerations  Yes  No The study3 will be conducted in compliance with ICH guidelines and with all applicable Yes federal No (including4 21 CFR parts 56 & 50), state or local laws.  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______13.2.1 Written Informed consent Provision of written informed consent must be obtained prior to any study-related procedures. The Principal Inclusion Investigator Criteria: will ALL ensure questions that the subjectmust be is answered given full “YES”and adequate in oral and written informationorder about for the a patient nature, to purpose, be eligible. possible risks and benefits of the study as well as the subject’s1 financial responsibility. Subjects must also be notified that they are free Yesto discontinue  No from the study at any time. The subject should be given the opportunity to ask questions and be 2 Yes No allowed time to consider the information provided.   3  Yes  No The original,4 signed written Informed Consent Form must be kept with the Research Yes Chart  No in conformance with the institution’s standard operating procedures. A copy of the signed written 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Informed Consent Form must be given to the subject. Additionally, documentation of the consenting process should be located in the research chart. Inclusion Criteria: ALL questions must be answered “YES” in 13.2.2 Subject Data Protection order for a patient to be eligible. In accordance with the Health Information Portability and Accountability Act (HIPAA), a 1  Yes  No subject must sign an authorization to release medical information to the sponsor and/or allow the 2 sponsor, a regulatory authority, or Institutional Review Board access to subject’s Yes medical  No information3 that includes all hospital records relevant to the study, including subjects’ Yes medical  No history.4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______13.2.3 Retention of records The Principal Investigator of The Case Comprehensive Cancer Center supervises the retention of all documentation Inclusion of Criteria: adverse events,ALL questions records of must study be drug answered receipt “YES”and dispensation, in and all IRB correspondenceorder for for a aspatient long to as be neededeligible. to comply with local, national and international regulations.1 No records will be destroyed until the Principal Investigator confirms destruction is permitted.  Yes  No 2  Yes  No 13.2.43 Audits and inspections  Yes  No Authorized4 representatives of the sponsor, a regulatory authority, an Independent Yes  Ethics No Committee (IEC) or an Institutional Review Board (IRB) may visit the site to perform audits or 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______inspections, including source data verification. The purpose of an audit or inspection is to systematically and independently examine all study-related activities and documents to determine Inclusion whether Criteria: these activities ALL questions were conducted, must be andanswered data were“YES” recorded, in analysed, and accuratelyorder reported for aaccording patient to to be the eligible. protocol, Good Clinical Practice (GCP), guidelines of the International1 Conference on Harmonization (ICH), and any applicable regulatory requirements. For multi-center studies, participating sites must inform the sponsor-investigator Yes of pending  No audits.2  Yes  No 3  Yes  No 14.0 4STATISTICAL CONSIDERATIONS  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Investigators must amend a protocol in order to capture additional data. Data can not be collected until the amendment has received IRB approval and will pertain only to data captured from that Inclusiontime period Criteria: forward. ALL questions must be answered “YES” in order for a patient to be eligible. This section1 should be developed in close collaboration with the study biostatistician: at an early stage in protocol development. SEE GUIDANCE DOCUMENT FOR REFERRALS Yes  No 2  Yes  No The outline3 below is modified from CTEP protocol templates for standard Phase I Yesand II studies  No (http://ctep.info.nih.gov/protocolDevelopment/default.htm#protocol_development),4  Yes and is meant No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______to provide a rough guideline as to what information should be included, recognizing that this will depend on the particular protocol and design used. Inclusion Criteria: ALL questions must be answered “YES” in  Describeorder the for study a patient design. to Thisbe eligible. includes: the objectives of the trials (primary, secondary and exploratory) 1 o  Yes  No . the associated endpoint(s) 2 . please include time frames for completing associated endpoints Yes  No 3 o the method of dose escalation (e.g. “3+3”; accelerated titration; Yes continual  No 4 reassessment method (CRM)).  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______o If the primary goal of the trial is to identify a maximum tolerated dose (or optimal biologic dose, or both) provide a precise definition of it or reference the Inclusionappropriate Criteria: protocol ALL section.questions must be answered “YES” in ordero If for the a trial patient is randomized to be eligible. indicate the proportion of subjects to be accrued to each 1 dose level (e.g. equal randomization).  Yes  No 2  Provide a statistical justification for the number of subjects to be enrolled Yes based on Nothe 3primary goal(s) of the trial.  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______ If correlative studies are being performed address the suitability of the proposed sample size to obtain meaningful results (even if the goal of such studies is hypothesis generating). Also Inclusion include the Criteria: objectives, ALL endpoints, questions and must any bemethods answered not described “YES” in in correlative researchorder section for a patientof the protocol. to be eligible. 1  Yes  No  Describe how the primary and secondary/correlative endpoints will be analyzed (e.g. 2 parametric versus non-parametric methods; one versus two-sided statistical tests; Yes the  No 3confidence limits that will be used for estimation).  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______o If correlative studies are included, address whether or not adjustments to p-values will be made for multiple comparisons; and if appropriate the method to be used. Inclusion Criteria: ALL questions must be answered “YES” in  Provideorder an for estimate a patient of the to accrualbe eligible. rate. 1  Yes  No 2  Yes  No 3  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______REFERENCES

Please provideInclusion the citations Criteria: for ALL all publications questions mustreferenced be answered in the text. “YES” in order for a patient to be eligible. Publications1 should be organized as any standard bibliography using AMA style Yes formatting  No as presented below. 2  Yes  No Number.3 Last name followed by initial of first name. Title of article in sentence format. Yes Title  No of Journal4 in Abbreviated Title Format. Month Year published;edition or volume:page-page. Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Example: Inclusion Criteria: ALL questions must be answered “YES” in 1. orderHensen, for aDE, patient Albores-Savvedra to be eligible. J, Corle D. Carcinoma of the gallbladder, histologic types, stage of disease and survival rates. Cancer 1992;70:1493-1497. 1  Yes  No 2  Yes  No 3  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Class Symptoms

APPENDIX B

Class Symptoms

APPENDIX B

Inclusion Criteria: ALL questions must be answered “YES” in order for a patient to be eligible. 1  Yes  No 2 APPENDIX I  Yes  No 3  Yes  No 4 PERFORMANCE STATUS CRITERIA  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______ECOG Performance Status Scale Karnofsky Performance Scale Grade Description Percent Description Inclusion Criteria: ALL questions must be answeredNormal, “YES” no complaints,in no 0 Normalorder for activity. a patient Full toactive, be eligible. able to 100 evidence of disease. carry on all pre-disease performance 1  Yes  No without restriction. Able to carry on normal activity; 2 90 minor signs or symptoms Yes of  No 3 disease.  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Symptoms, but ambulatory. Restricted Normal activity with effort; some 1 in physically strenuous activity, but 80 signs or symptoms of disease. ambulatory and able to carry out work Inclusion Criteria: ALL questions must be answeredCares “YES” for self, in unable to carry on oforder a light for or a sedentary patient to nature be eligible. (e.g., light housework, office work). 70 normal activity or to do active 1 work.  Yes  No 2 In bed < 50% of the time. Requires occasional Yes assistance,  No 2 Ambulatory and capable of all self- 60 but is able to care for most of 3  Yes  No care, but unable to carry out any work his/her needs. 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______activities. Up and about more than Requires considerable assistance 50% if waking hours. 50 and frequent medical care. InInclusion bed > 50% Criteria: of the time. ALL Capablequestions of must be answeredDisabled, “YES” requires in special care 3 onlyorder limited for a self-care,patient to confined be eligible. to bed 40 and assistance. 1 or chair more than 50% of waking  Yes  No 2 hours. Severely disabled, hospitalization 30 indicated. Death not Yes imminent.  No 3  Yes  No 4 Very sick, hospitalization Yes  No 4 5 20 indicated. Death not Yes imminent.  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______100% bedridden. Completely Moribund, fatal processes disabled. Cannot carry on any self- 10 progressing rapidly. care.Inclusion Totally Criteria: confined ALL to bed questions or chair. must be answered “YES” in 5 Dead.order for a patient to be eligible. 0 Dead 1  Yes  No 2  Yes  No 3  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Inclusion Criteria: ALL questions must be answered “YES” in order for a patient to be eligible. 1  Yes  No 2 APPENDIX II  Yes  No 3  Yes  No 4 SUBJECT PILL DIARY  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Revise the areas in red to fit the protocol. Delete #2 under instructions and the second column of pills if only one mg or one agent is used. Add additional columns and rows as needed for multiple agents/longer cycles. Subject Name ______Protocol #______Subject Study ID ______Inclusion Criteria: ALL questions must be answered “YES” in Cycle #: ______Month #: ______order for a patient to be eligible. INSTRUCTIONS FOR THE SUBJECT: 1. You will1 take # of tablets of ____ mg record agent pills each day. Take the tablets [on an empty stomach Yes / with No a full glass (8 ox)2 of water / before or 2 hours after meals / with or without food, as you wish]. 2. You will take # of tablets of ____ mg record agent pills each day. Take the tablets [on an empty stomach Yes / with No a full glass (8 ox)3 of water / before or 2 hours after meals / with or without food, as you wish].  Yes  No 3. Record4 the date, the number of tablets you took, and what time you took them. 4. If you have any comments please record them in the “Comments” column below.  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______5. Please bring your pill bottle and this form to your physician when you come for your next appointment. 6. Please sign your name at the bottom of the diary.

# of _____ mg record agent # of _____ mg record agent Date Day Comments Inclusion Criteria:pills and ALLtime takenquestions mustpills be and answered time taken “YES” in order1 for a patient to be eligible. 1 2  Yes  No 2 3  Yes  No 4 3 5  Yes  No 4 6  Yes  No 5 7  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______8 9 10 Inclusion Criteria: ALL questions must be answered “YES” in 11 order for a patient to be eligible. 12 1 13  Yes  No 2 14  Yes  No 15 3  Yes  No 16 4 17  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______18 19 20 Inclusion Criteria: ALL questions must be answered “YES” in 21 order for a patient to be eligible. 22 1 23  Yes  No 2 24  Yes  No 25 3  Yes  No 26 4 27  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______28 Add/remove days as needed Subject’s Signature: ______Date: ______Inclusion Criteria: ALL questions must be answered “YES” in order for a patient to be eligible. 1  Yes  No 2  Yes  No 3  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______APPENDIX III

InclusionSUBJECT Criteria: PILLALL questionsDIARY FOR must TWICE be answered DAILY “YES” DOSING in Add or delete columnsorder forand arows patient and torevise be eligible. the information in red as appropriate for the trial. Subject Name1 ______Subject Study ID ______Today’s date ___/___/___ Drug ______Cycle #:______ Yes  No INSTRUCTIONS2 FOR THE SUBJECT:  Yes  No 1. Complete3 one form every 4 weeks (one treatment cycle).  Yes  No 2. You will take record agent tablets twice each day about 12 hours apart. Take the tablets [on an empty stomach / with a full glass 4(8 ox) of water / before or 2 hours after meals / with or without food, as you wish].  Yes  No Morning5 dose: take # of ____ mg tablet(s) [if applicable, and # of ____ mg tablet(s)]  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______Evening dose: take # of ____ mg tablet(s), [if applicable, and # of ____ mg tablet(s)] 3. Record the date, the number of tablets of each size that you took, and what time you took them. 4. If you have any comments or notice any side effects, please record them in the “Comments” column. 5. Please bring Inclusion this form and Criteria: your bottle ALL(s) of recordquestions agen tomust your bephysician answered when you“YES” return in for each appointment. 6. Please sign yourorder name for at a the patient bottom toof thebe diary.eligible. 1 Time of # of tablets taken # of tablets taken Time of evening  Yes  No Day Date morning 2 ______dose ______Comments dose mg mg mg mg  Yes  No 1 3  Yes  No 2 4  Yes  No 3 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______4 5 6 7 Inclusion Criteria: ALL questions must be answered “YES” in 8 order for a patient to be eligible. 9 1  Yes  No 10 2  Yes  No 11 12 3  Yes  No 13 4  Yes  No 14 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______15 16 17 18 Inclusion Criteria: ALL questions must be answered “YES” in 19 order for a patient to be eligible. 20 1  Yes  No 21 2  Yes  No 22 23 3  Yes  No 24 4  Yes  No 25 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Class Symptoms

APPENDIX B

Physician ______Study ID #______26 27 28 Add/remove days as needed Inclusion Criteria: ALL questions must be answered “YES” in Subject’s orderSignature: for a ______patient to be eligible. Date: ______1  Yes  No 2  Yes  No 3  Yes  No 4  Yes  No 5  Yes  No 6  Yes  No 7  Yes  No 8  Yes  No 9  Yes  No 10  Yes  No

Treating Physician/ PI ______Date ______