S1505 Page 1 Version Date 9/4/2020 PRIVILEGED COMMUNICATION Activation Date October 12, 2015 FOR INVESTIGATIONAL USE ONLY SWOG TITLE A RANDOMIZED PHASE II STUDY OF PERIOPERATIVE mFOLFIRINOX VERSUS GEMCITABINE/NAB-PACLITAXEL AS THERAPY FOR RESECTABLE PANCREATIC ADENOCARCINOMA NCT #02562716 STUDY CHAIRS: AGENTS: Davendra P.S. Sohal, M.D., M.P.H. (Medical IND-Exempt Agents: Cleveland Clinic Oncology) Fluorouracil (5-FU, Adrucil®) (NSC-19893) 9500 Euclid Ave – R35 Gemcitabine hydrochloride (Gemzar®) Cleveland, OH 44195 (NSC-613327) Phone: 216/444-8258 Irinotecan (Camptosar®) (NSC-616348) FAX: 216/444-9464 nab-Paclitaxel (NSC-736631) E-mail: [email protected] Oxaliplatin (Eloxatin) (NSC-266046) Syed Ahmad, M.D. (Surgery) BIOSTATISTICIANS: University of Cincinnati Medical Center 231 Albert Sabin Way, ML #0558 Katherine A. Guthrie, Ph.D. Cincinnati, OH 45267 Danika Lew, M.S. Phone: 513/558-7866 SWOG Statistical Center FAX: 513/584-0459 Fred Hutchinson Cancer Research Center E-mail: [email protected] 1100 Fairview Avenue N, M3-C102 P.O. Box 19024 Namita Gandhi, M.D. (Radiology) Seattle, WA 98109-1024 Cleveland Clinic Phone: 206/667-4623 9500 Euclid Ave FAX: 206/667-4408 Cleveland, OH 44195 E-mail: [email protected] Phone: 216/444-3682 E-mail [email protected] FAX: 216/636-1699 E-mail: [email protected] Philip A. Philip, M.D., Ph.D., F.R.C.P. Karmanos Cancer Center (Medical Oncology) Wayne State University 4100 John R Street 4HWCRC Detroit, MI 48201 Phone: 313/576-8728 FAX:313/576-8729 E-Mail: [email protected] Andrew M. Lowy, M.D., F.A.C.S. (Surgery) University of California, San Diego Moores Cancer Center 3855 Health Sciences Dr., #0987 La Jolla, CA 92093 Phone: 858/822-2124 FAX: 858/534-4813 E-mail: [email protected] S1505 Page 2 Version Date 9/4/2020 NCTN INVESTIGATORS: Andrea Wang-Gillam M.D., Ph.D. (ALLIANCE) Washington University in St. Louis Phone: 314-362-5740 Fax: 314-362-7086 E-mail: [email protected] M. Shaalan Beg, M.D. (ECOG-ACRIN) UT Southwestern Medical Center Phone: 214/648-4180 FAX: 214/648-1955 E-mail: [email protected] PARTICIPANTS ALLIANCE/Alliance for Clinical Trials in Oncology ECOG-ACRIN/ECOG-ACRIN Cancer Research Group NRG/NRG Oncology SWOG/SWOG S1505 Page 3 Version Date 9/4/2020 TABLE OF CONTENTS TITLE ......................................................................................................................................................... 1 PARTICIPANTS ............................................................................................................................................ 2 TABLE OF CONTENTS ............................................................................................................................... 3 CANCER TRIALS SUPPORT UNIT (CTSU) ADDRESS AND CONTACT INFORMATION ....................... 5 SCHEMA ....................................................................................................................................................... 6 1.0 OBJECTIVES .................................................................................................................................. 7 1.1 Primary Objectives ........................................................................................................................... 7 1.2 Secondary Objectives ...................................................................................................................... 7 1.3 Translational Objectives ................................................................................................................... 7 2.0 BACKGROUND ............................................................................................................................... 7 3.0 DRUG INFORMATION .................................................................................................................... 9 3.1 Fluorouracil (5-FU, Adrucil ®) (NSC-19893) .................................................................................... 9 3.2 Gemcitabine hydrochloride (Gemzar®) (NSC-613327) ................................................................. 11 3.3 Irinotecan (Camptosar®) (NSC-616348) ....................................................................................... 13 3.4 Nab-paclitaxel (Abraxane®) (NSC-736631) ................................................................................... 14 3.5 Oxaliplatin (Eloxatin®) (NSC-266046) ........................................................................................... 18 4.0 STAGING CRITERIA ..................................................................................................................... 20 5.0 ELIGIBILITY CRITERIA ................................................................................................................ 21 5.1 Disease Related Criteria ................................................................................................................ 21 5.2 Prior/Concurrent Therapy Criteria .................................................................................................. 22 5.3 Clinical/Laboratory Criteria ............................................................................................................. 22 5.4 Specimen Submission Criteria ....................................................................................................... 22 5.5 Regulatory Criteria ......................................................................................................................... 23 6.0 STRATIFICATION FACTORS ....................................................................................................... 23 7.0 TREATMENT PLAN ...................................................................................................................... 23 7.1 Pre-Medication and Concomitant Medications and Care .............................................................. 23 7.2 Arm 1: mFOLFIRINOX ................................................................................................................... 24 7.3 Arm 2: Gemcitabine/nab-Paclitaxel ................................................................................................ 24 7.4 Surgery ........................................................................................................................................... 24 7.5 Radiation ........................................................................................................................................ 27 7.6 Criteria for Removal from Protocol Treatment ............................................................................... 27 7.7 Discontinuation of Treatment ......................................................................................................... 27 7.8 Follow-Up Period ............................................................................................................................ 27 8.0 TOXICITIES TO BE MONITORED AND DOSE MODIFICATIONS .............................................. 28 8.1 NCI Common Terminology Criteria for Adverse Events ................................................................ 28 8.2 General Considerations ................................................................................................................. 28 8.3 Dose Modifications for Arm 1: mFOLFIRINOX .............................................................................. 28 8.4 Dose Modifications for Arm 2: Gemcitabine/nab-Paclitaxel ........................................................... 31 8.5 Dose Modification Contacts ........................................................................................................... 32 8.6 Adverse Event Reporting ............................................................................................................... 33 9.0 STUDY CALENDAR ...................................................................................................................... 34 9.1 Arm 1: mFOLFIRINOX ................................................................................................................... 34 10.0 CRITERIA FOR EVALUATION AND ENDPOINT ANALYSIS ..................................................... 37 10.1 Measurability of Lesions................................................................................................................. 37 10.2 The definitions for the resection classification that should be utilized in operative notes include: 38 10.3 Objective Status at Each Disease Evaluation ................................................................................ 38 10.4 Best Response ............................................................................................................................... 40 10.5 Performance Status ....................................................................................................................... 40 10.6 Pathologic Response ..................................................................................................................... 41 10.7 Loco-regional recurrence ............................................................................................................... 41 10.8 Distant recurrence .......................................................................................................................... 41 10.9 Disease-Free Survival (DFS) ......................................................................................................... 41 10.10 Time to Death ................................................................................................................................