SUMMARY OF CHANGES For Protocol Amendment #11 to: 9974 NCI Protocol #: 9974 Local Protocol #: 17-732 NCI Version Date: 13 May 2019 Protocol Date: 13 May 2019 I. Protocol Changes following Request for Rapid Amendment # Section Page(s) Change The informed consent document was modified as a result of the CTEP RRA for Olaparib and latest version of the CAEPR. 1 ICD - The protocol version date was also updated in the consent document. The protocol version date was updated on the cover page and Protocol throughout the protocol document. Minor typographical revisions 2 - document were made throughout the protocol document. These changes are tracked. The Comprehensive Adverse Events and Potential Risks Lists (CAEPRs) were updated to reflect the latest CAEPR for Olaparib (Version 2.4, April 24, 2019). These changes are a result of the CTEP RRA for Olaparib. The following changes were made to the CAEPR: • Increase in Risk Attribution: • Changed to Rare but Serious from Also Reported on Cediranib Trials But With Insufficient Evidence for Attribution: Platelet count decreased; White blood cell decreased 3 7.1 69 • Provided Further Clarification: • A new note has been added to the CAEPR; “NOTE: New Primary Malignancies other than MDS/AML New primary malignancies have been reported in <1% of patients. There were other contributing factors/potential alternative explanations for the development of the new primary malignancy in all cases, including documented BRCA mutation, treatment with radiotherapy and extensive previous chemotherapy including carboplatin, taxanes, anthracyclines and other alkylating and DNA damaging agents. Most are not attributed to olaparib.” 1 NCI Protocol #:9974 Version Date: 13 May 2019 NCI Protocol #: 9974 Local Protocol #: 17-732 ClinicalTrials.gov Identifier: NCT02899728 TITLE: A phase II study of olaparib plus cediranib in combination with standard therapy for small cell lung cancer Corresponding Organization: LAO-MA036 / Dana-Farber Harvard Cancer Center Principal Investigator: Jacob Sands, MD Dana-Farber Cancer Institute 450 Brookline Avenue Boston, MA 02215 Phone: 617-632-6049 Fax: 617-632-6485 [email protected] Participating Organizations (Only the participating LAOs should be listed.) LAO-11030 / University Health Network Princess Margaret Cancer Center LAO LAO-CA043 / City of Hope Comprehensive Cancer Center LAO LAO-CT018 / Yale University Cancer Center LAO LAO-MA036 / Dana-Farber - Harvard Cancer Center LAO LAO-MD017 / JHU Sidney Kimmel Comprehensive Cancer Center LAO LAO-MN026 / Mayo Clinic Cancer Center LAO LAO-NC010 / Duke University - Duke Cancer Institute LAO LAO-NJ066 / Rutgers University - Cancer Institute of New Jersey LAO LAO-OH007 / Ohio State University Comprehensive Cancer Center LAO LAO-PA015 / University of Pittsburgh Cancer Institute LAO LAO-TX035 / University of Texas MD Anderson Cancer Center LAO LAO-NCI / National Cancer Institute LAO 2 NCI Protocol #:9974 Version Date: 13 May 2019 Study Coordinator: Sarah Clifford, MPH 450 Brookline Avenue, LGGB Boston, MA 02215 Phone: 617-632-5438 Fax: 617-632-6485 [email protected] NCI-Supplied Agent(s): Olaparib (AZD2281, NSC 747856), cediranib (AZD2171, NSC 732208) Other Agent(s): Cisplatin (Commercial), Carboplatin (Commercial), Etoposide (Commercial) IND Sponsor: DCTD, NCI Protocol Type / Version # / Version Date: Original / Version 5 / 04 April 2017 Amendment 3 / Version 6 / 03 October 2017 Amendment 4 / Version 7 / 18 October 2017 Amendment 6 / Version 8 / 21 May 2018 Amendment 7 / Version 9 / 31 Jul 2018 Amendment 8 / Version 10 / 12 Oct 2018 Amendment 9 / Version 11 / 11 Jan 2019 Amendment 10 / Version 12 / 17 Jan 2019 Amendment 11 / Version 13 / 13 May 2019 3 NCI Protocol #:9974 Version Date: 13 May 2019 SCHEMA OVERALL SCHEMA PLANNED OBJECTIVES 4 NCI Protocol #:9974 Version Date: 13 May 2019 TABLE OF CONTENTS SCHEMA ............................................................................................................................... 4 1. OBJECTIVES .............................................................................................................. 8 1.1 Primary Objectives............................................................................................ 8 1.2 Secondary Objectives ........................................................................................ 8 2. BACKGROUND ......................................................................................................... 8 2.1 Small Cell Lung Cancer .................................................................................... 8 2.2 CTEP IND Agents .......................................................................................... 11 2.3 Other Agents................................................................................................... 22 2.4 Correlative Studies Background....................................................................... 22 3. PATIENT SELECTION ............................................................................................. 27 3.1 Eligibility Criteria ........................................................................................... 28 3.2 Exclusion Criteria ........................................................................................... 29 3.3 Inclusion of Women and Minorities ................................................................. 32 4. REGISTRATION PROCEDURES ............................................................................. 32 4.1 Investigator and Research Associate Registration with CTEP ........................... 32 4.2 Site Registration.............................................................................................. 33 4.3 Patient Registration ......................................................................................... 35 4.4 General Guidelines.......................................................................................... 36 5. TREATMENT PLAN ................................................................................................ 36 5.1 Agent Administration ...................................................................................... 36 5.2 General Concomitant Medication and Supportive Care Guidelines ................... 40 5.3 Duration of Therapy ........................................................................................ 45 5.4 Duration of Follow Up .................................................................................... 46 6. DOSING DELAYS/DOSE MODIFICATIONS........................................................... 47 6.1 Dose Modification Guidelines ......................................................................... 47 6.2 Toxicity Management Guidelines .................................................................... 48 7. ADVERSE EVENTS: LIST AND REPORTING REQUIREMENTS.......................... 63 7.1 Comprehensive Adverse Events and Potential Risks Lists (CAEPRs) ............... 63 7.2 Adverse Event Characteristics ......................................................................... 71 7.3 Expedited Adverse Event Reporting ................................................................ 71 7.4 Routine Adverse Event Reporting.................................................................... 74 7.5 Reporting of Pregnancy and Overdose ............................................................. 74 7.6 Secondary Malignancy .................................................................................... 74 7.7 Second Malignancy......................................................................................... 74 8. PHARMACEUTICAL INFORMATION .................................................................... 75 8.1 CTEP IND Agents .......................................................................................... 75 5 NCI Protocol #:9974 Version Date: 13 May 2019 8.2 Commercial Agents......................................................................................... 81 9. BIOMARKER, CORRELATIVE, AND SPECIAL STUDIES ..................................... 84 9.1 Archival Tumor Tissue Collection - Exploratory/Ancillary Correlative Studies............................................................................................................ 84 9.2 Specimen requirements ................................................................................... 84 9.3 Blood-Based Exploratory/Ancillary Correlative Studies ................................... 92 9.4 Fresh Tumor Tissue Collection - Exploratory/Ancillary Correlative Studies............................................................................................................ 95 10. STUDY CALENDAR ................................................................................................ 96 11. MEASUREMENT OF EFFECT ............................................................................... 101 11.1 Antitumor Effect – Solid Tumors................................................................... 101 12. STUDY OVERSIGHT AND DATA REPORTING / REGULATORY REQUIREMENTS ................................................................................................... 107 12.1 Study Oversight ............................................................................................ 107 12.2 Data Reporting.............................................................................................. 108 12.3 CTEP Multicenter Guidelines ........................................................................ 110 12.4 Collaborative