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(Research Base)* Study Co ALLIANCE FOR CLINICAL TRIALS IN ONCOLOGY ALLIANCE A221101 A PHASE III RANDOMIZED, DOUBLE-BLIND PLACEBO CONTROLLED STUDY OF ARMODAFINIL (NUVIGIL®) TO REDUCE CANCER-RELATED FATIGUE IN PATIENTS WITH HIGH GRADE GLIOMA Study Chairs: Alyx B. Porter Umphrey, M.D. (Research Base)* Study Co-chairs: Statisticians: Drug Availability Drug Company Supplied: Armodafinil (Exempt IND 116927) *Investigator having NCI responsibility for this protocol √Study contributor(s) not responsible for patient care. ClinicalTrials.gov Identifier: NCT01781468 Participating NCTN Organizations Alliance/Alliance for Clinical Trials in Oncology (lead) ECOG ACRIN/ ECOG-ACRIN Medical Research Foundation, Inc NRG/NRG Oncology Foundation, Inc SWOG/SWOG NCI Version Date: 9/24/2018 Update #7 1 Alliance A221101 Cancer Trials Support Unit (CTSU) Address and Contact Information For regulatory requirements: For patient enrollments: For study data submission Regulatory documentation must be Please refer to the patient Legacy NCCTG sites will submitted to the CTSU via the enrollment section of the submit electronic CRFs via: Regulatory Submission Portal. protocol for instructions on NCCTG Remote Data Entry Regulatory Submission Portal: (Sign using the Oncology Patient System. in at , and select Enrollment Network (OPEN) the Regulatory Submission sub-tab which can be accessed at Sites not previously affiliated under the Regulatory tab.) with NCCTG will submit or paper CRFs to: Institutions with patients waiting that . are unable to use the Portal should alert the CTSU Regulatory Office Contact the CTSU Help Desk immediately at to with any OPEN-related receive further instruction and questions at support. Contact the CTSU Regulatory Help Do not submit study data or Desk at for forms to CTSU Data regulatory assistance. Operations. Do not copy the CTSU on data submissions. The most current version of the study protocol and all supporting documents must be downloaded from the protocol-specific Web page of the CTSU Member Web site located at . Access to the CTSU members’ website is managed through the Cancer Therapy and Evaluation Program - Identity and Access Management (CTEP-IAM) registration system and requires user log on with CTEP-IAM username and password. Permission to view and download this protocol and its supporting documents is restricted and is based on person and site roster assignment housed in the CTSU RSS. For clinical questions (i.e. patient eligibility or treatment-related) see the Protocol Contacts, Page 3. For non-clinical questions (i.e. unrelated to patient eligibility, treatment, or clinical data submission) contact the CTSU Help Desk by phone or e-mail: CTSU General Information Line – , or . All calls and correspondence will be triaged to the appropriate CTSU representative. The CTSU Web site is located at . NCI Version Date: 9/24/2018 Update #7 2 Alliance A221101 Protocol Resources Data Manager Protocol Coordinator Expedited Adverse Event Reporting OPEN (Oncology Patient Enrollment Network) A221101 Nursing Contacts Protocol-related questions may be directed as follows: Questions Contact (via email) Questions regarding patient eligibility, treatment, Study Chair, Nursing Contact, Protocol and dose modification: Coordinator, and (where applicable) Data Manager Questions related to data submission or patient Data Manager follow-up: Questions regarding the protocol document and Protocol Coordinator model informed consent: Alliance Regulatory Inbox Questions related to IRB review Questions regarding CTEP-AERS reporting: Alliance Pharmacovigilance Inbox NCI Version Date: 9/24/2018 Update #7 3 Alliance A221101 Schema Randomization Armodafinil Placebo Armodafinil 150mg q.d. x 8 weeks q.d.x 8 weeks 250mg q.d. x 8 weeks Off Study Unacceptable adverse events or patient refusal at any time Off Study Cycle 1 length = 4 weeks Cycle 2 length = 4 weeks NOTE: Cycle is a data management tool to facilitate consistent remote data entry. Generic name: Armodafinil Generic name: Placebo Brand name(s): Nuvigil® Brand name(s): Alliance Abbreviation: Alliance Abbreviation: Availability: Alliance Research Base pharmacy Availability: Alliance Research Base pharmacy NCI Version Date: 9/24/2018 Update #7 4 Alliance A221101 Table of Contents 1.0 INTRODUCTION ........................................................................................................................... 7 1.1 Background .................................................................................................................................................. 7 1.2 Evidence-Based Interventions ...................................................................................................................... 9 1.3 Mechanisms of Newer Psychostimulants and Rationale for Armodafinil (Nuvigil) .................................. 12 1.4 Study rationale ........................................................................................................................................... 14 2.0 GOALS........................................................................................................................................... 14 2.1 Primary ....................................................................................................................................................... 14 2.2 Secondary ................................................................................................................................................... 14 3.0 PATIENT ELIGIBILITY ............................................................................................................ 15 3.1 Inclusion Criteria ........................................................................................................................................ 15 3.2 Exclusion Criteria ...................................................................................................................................... 15 4.0 TEST SCHEDULE ....................................................................................................................... 18 4.1 Neurocognitive Testing .............................................................................................................................. 19 5.0 STRATIFICATION FACTORS .................................................................................................. 22 5.1 Concomitant Chemotherapy: Yes vs. No .................................................................................................. 22 5.2 Age: < 60 vs. ≥60 ...................................................................................................................................... 22 5.3 Corticosteroid use: Yes vs. No .................................................................................................................. 22 5.4 Gender: Male vs. Female .......................................................................................................................... 22 6.0 REGISTRATION/RANDOMIZATION PROCEDURES ........................................................ 22 6.1 Registration Requirements ......................................................................................................................... 22 6.2 CTEP Registration Procedures ................................................................................................................... 22 6.3 Site Registration Requirements – IRB Approval ....................................................................................... 23 6.4 Patient Randomization ............................................................................................................................... 25 6.5 Procedures for Double-Blinding the Treatment Assignment ..................................................................... 26 7.0 PROTOCOL TREATMENT ...................................................................................................... 28 7.1 Treatment Schedule .................................................................................................................................... 28 7.2 Unblinding Procedures ............................................................................................................................... 28 8.0 DOSAGE MODIFICATION BASED ON ADVERSE EVENTS ............................................. 29 9.0 ANCILLARY TREATMENT/SUPPORTIVE CARE ............................................................... 29 10.0 ADVERSE EVENT (AE) REPORTING AND MONITORING .............................................. 29 10.1 Routine Adverse Event Reporting .............................................................................................................. 29 10.2 CTCAE Routine Study Reporting Requirements ....................................................................................... 30 10.3 Expedited adverse event reporting (CTEP-AERS) .................................................................................... 30 10.4 Contact Information for NCI Safety Reporting .......................................................................................... 33 10.5 Other Required Expedited Reporting ......................................................................................................... 34 10.6 Adverse events to be graded at each evaluation. ........................................................................................ 34 11.0 TREATMENT EVALUATION ................................................................................................... 34 11.1 Patient Self-Report Measures
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