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Phase II Trial of Nintedanib in Patients with Advanced Esophagogastric Cancer PROTOCOL FACE PAGE for MSKCC THERAPEUTIC/DIAGNOSTIC PROTOCOL

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Phase II Trial of Nintedanib in Patients with Advanced Esophagogastric Cancer PROTOCOL FACE PAGE for MSKCC THERAPEUTIC/DIAGNOSTIC PROTOCOL Memorial Sloan Kettering Cancer Center IRB#: 14-094 A (5) Approved: 27-DEC-2016 Phase II trial of Nintedanib in patients with advanced esophagogastric cancer PROTOCOL FACE PAGE FOR MSKCC THERAPEUTIC/DIAGNOSTIC PROTOCOL Principal Yelena Y. Janjigian, MD Medicine Investigator/Department: Co-Principal David H. Ilson, MD, PhD Medicine Investigator(s)/Department: Elizabeth S. Won, MD Medicine Investigator(s)/Department: Marinela Capanu, PhD Epidemiology/Biostatistics Robert Lefkowitz, MD Radiology Marc Z. Simmons, MD Radiology Ghassan Abou-Alfa, MD Medicine Andrea Cercek, MD Medicine Andrew Epstein, MD Medicine James Harding, MD Medicine David Kelsen, MD Medicine Nancy Kemeny, MD Medicine Geoffrey Ku, MD Medicine Maeve Lowery, MD Medicine Eileen O’Reilly, MD Medicine Diane Reidy-Lagunes, MD Medicine Leonard Saltz, MD Medicine Neil Segal, MD, PhD Medicine Zsofia Stadler, MD Medicine Kenneth H. Yu, MD Medicine Anna Varghese, MD Medicine Rona Yaeger, MD Medicine Nitya Raj, MD Medicine Ellen Hollywood, NP Nursing Maria Pacis, NP Nursing Erica Kaufmann, NP Nursing Sree Chalasani, MD Medicine Han Xiao, MD Medicine Afsheen Iqbal, MD Medicine Leticia Smith, APN Nursing Janet Cogswell, CRN Nursing Avni Desai, MD Medicine John Fiore, MD Medicine Stuart Lichtman, MD Medicine Jahan Aghalar, MD Medicine Juliana Eng, MD Medicine Jia Li, MD Medicine Wanqing Iris Zhi, MD, PhD Medicine Adriana Olivo, NP Nursing Lori Gofter, CRN Nursing Arlyn Apollo, MD Medicine Page 1 of 36 Memorial Sloan Kettering Cancer Center IRB#: 14-094 A (5) Approved: 27-DEC-2016 Pamela Drullinsky, MD Medicine Zoe Goldberg, MD Medicine Tiffany Troso-Sandoval, MD Medicine Kenneth Ng, MD Medicine Erin Scansarole, CRN Nursing Krysti Corrado, CRN Nursing Philip Caron, MD Medicine Alice Zervoudakis, MD Medicine Parisa Momtaz, MD Medicine Chung-Han Lee, MD Medicine Gloria Wasilewski, CRN Nursing Jason Konner, MD Medicine Serena Wong, MD Medicine Jacqueline Bromberg, MD Medicine PhD Colette Owens, MD Medicine Loren Michel, MD Medicine Azadeh Namakydoust, MD Medicine Marina Shcherba, DO Medicine Consenting Yelena Y. Janjigian, MD Medicine Professional(s)/Department: David H. Ilson, MD, PhD Medicine Ghassan Abou-Alfa, MD Medicine Andrea Cercek, MD Medicine Andrew Epstein, MD Medicine James Harding, MD Medicine David Kelsen, MD Medicine Nancy Kemeny, MD Medicine Geoffrey Ku, MD Medicine Maeve Lowery, MD Medicine Eileen O’Reilly, MD Medicine Diane Reidy-Lagunes, MD Medicine Leonard Saltz, MD Medicine Neil Segal, MD, PhD Medicine Zsofia Stadler, MD Medicine Kenneth H. Yu, MD Medicine Anna Varghese, MD Medicine Rona Yaeger, MD Medicine Elizabeth S. Won, MD Medicine Nitya Raj, MD Medicine Ellen Hollywood, NP Nursing Maria Pacis, NP Nursing Erica Kaufmann, NP Nursing Sree Chalasani, MD Medicine Han Xiao, MD Medicine Afsheen Iqbal, MD Medicine Avni Desai, MD Medicine John Fiore, MD Medicine Page 2 of 36 Memorial Sloan Kettering Cancer Center IRB#: 14-094 A (5) Approved: 27-DEC-2016 Stuart Lichtman, MD Medicine Jahan Aghalar, MD Medicine Juliana Eng, MD Medicine Jia Li, MD Medicine Wanqing Iris Zhi, MD, PhD Medicine Arlyn Apollo, MD Medicine Pamela Drullinsky, MD Medicine Zoe Goldberg, MD Medicine Tiffany Troso-Sandoval, MD Medicine Kenneth Ng, MD Medicine Philip Caron, MD Medicine Alice Zervoudakis, MD Medicine Parisa Momtaz, MD Medicine Chung-Han Lee, MD Medicine Jason Konner, MD Medicine Serena Wong, MD Medicine Jacqueline Bromberg, MD Medicine PhD Colette Owens, MD Medicine Loren Michel, MD Medicine Azadeh Namakydoust, MD Medicine Marina Shcherba, DO Medicine Please Note: A Consenting Professional must have completed the mandatory Human Subjects Education and Certification Program. OneMSK Sites Manhattan Basking Ridge Commack Monmouth Rockville Centre Westchester Memorial Sloan-Kettering Cancer Center 1275 York Avenue New York, New York 10065 Page 3 of 36 Memorial Sloan Kettering Cancer Center IRB#: 14-094 A (5) Approved: 27-DEC-2016 Table of Contents 1.0 PROTOCOL SUMMARY AND/OR SCHEMA ..................................................................... 5 2.0 OBJECTIVES AND SCIENTIFIC AIMS .................................................................................. 6 3.0 BACKGROUND AND RATIONALE .................................................................................... 6 4.0 OVERVIEW OF STUDY DESIGN/INTERVENTION ............................................................. 12 4.1 Design......................................................................................................................... 12 4.2 Intervention ................................................................................................................. 12 5.0 THERAPEUTIC/DIAGNOSTIC AGENTS ............................................................................. 13 6.0 CRITERIA FOR SUBJECT ELIGIBILITY .......................................................................... 14 6.1 Subject Inclusion Criteria ............................................................................................. 14 6.2 Subject Exclusion Criteria ............................................................................................ 14 7.0 RECRUITMENT PLAN ..................................................................................................... 15 8.0 PRETREATMENT EVALUATION ..................................................................................... 16 9.0 TREATMENT/INTERVENTION PLAN .................................................................................. 16 10.0 EVALUATION DURING TREATMENT/INTERVENTION ..................................................... 20 11.0 TOXICITIES/SIDE EFFECTS ................................................................................................ 23 12.0 CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT ....................... 25 13.0 CRITERIA FOR REMOVAL FROM STUDY ......................................................................... 26 14.0 BIOSTATISTICS ................................................................................................................... 27 15.0 RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION PROCEDURES27 15.1 Research Participant Registration .................................................................................... 27 15.2 Randomization .............................................................................................................. 28 16.0 DATA MANAGEMENT ISSUES ....................................................................................... 28 16.1 Quality Assurance ....................................................................................................... 28 16.2 Data and Safety Monitoring ......................................................................................... 28 17.0 PROTECTION OF HUMAN SUBJECTS ........................................................................... 29 17.1 Privacy ........................................................................................................................ 30 17.2 Serious Adverse Event (SAE) Reporting ..................................................................... 30 17.2.1 ................................................................................................................................... 31 18.0 INFORMED CONSENT PROCEDURES .............................................................................. 32 19.0 REFERENCES ...................................................................................................................... 33 20.0 APPENDICES ....................................................................................................................... 36 Page 4 of 36 Memorial Sloan Kettering Cancer Center IRB#: 14-094 A (5) Approved: 27-DEC-2016 1.01.0 PROTOCOL SUMMARY AND/OR SCHEMA Protocol title: Phase II trial of Nintedanib in patients with advanced esophagogastric cancer Study Objectives: This is a phase II study of Nintedanib in patients with metastatic or recurrent esophagogastric cancer. The goal of the study is to evaluate the efficacy of Nintedanib, an orally available triple kinase inhibitor targeting the receptors of the vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), and fibroblast growth factor (FGF) receptor pathways. The primary endpoint will be to evaluate the 6-month progression-free survival (PFS) of Nintedanib. With a total of 32 patients, we have 89% power to detect an improvement in the 6 month PFS from a historical control of 10% to 28%, with a type I and II error rate of 10%. Study population: Patients with metastatic or recurrent esophagogastric adenocarcinoma will be eligible. Patients will be allowed to have up to a maximum of one prior chemotherapy regimen for metastatic disease. Patients are allowed to have a maximum of two prior regimens if they previously received neoadjuvant/adjuvant chemotherapy or chemoradiotherapy for their initial localized disease. Study design: Single institution, open label, non-randomized, single arm phase II Number of patients: 32 Study drugs: Nintedanib, administered orally Dose and regimen: Nintedanib 200mg twice daily administered continuously. Patients will continue on treatment until progression of disease. Each cycle consists of 28 days. Page 5 of 36 Memorial Sloan Kettering Cancer Center IRB#: 14-094 A (5) Approved: 27-DEC-2016 2.1 OBJECTIVES AND SCIENTIFIC AIMS Primary objective: To evaluate the 6-month progression-free survival (PFS) of Nintedanib in patients with metastatic or recurrent esophagogastric adenocarcinoma.
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