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Hong, MD (MGH) &RRUGLQDWLQJ&HQWHUN/A Co-Investigators: Janet E. Murphy, MD Alec Kimmelman, M.D. Harvey Mamon, MD, PhD (DFCI) Lawrence Blaszkowsky, MD Michael Blake, MD Thomas DeLaney, MD Jeffrey Clark, MD Eunice Kwak, MD, PhD David Ryan, MD Andrew Zhu, MD, PhD Jill Allen, MD Jeffrey Meyerhardt, MD Robert J Mayer, MD Charles Fuchs, MD Peter Enzinger, MD Matthew Kulke, MD Pankaj Bhargava, MD Dushyant Sahani, MD Jennifer Wo, MD Lorraine Drapek, RN, FNP-BC Ryan Nipp, MD Theresa McDonnell, DNP, ACNP-BC Ann Donnelly, NP Rhaea Photopoulos, MS, ANP-BC Caroline Kuhlman, MS, NP, AOCNP Patricia Tammaro, NP Emily Olson, NP 6WDWLVWLFLDQ Beow Yeap, ScD, MGH 6WXG\&RRUGLQDWRU'DWD0DQDJHULeilana Ly, MGH 5HVSRQVLEOH5HVHDUFK1XUVH TBN CONFIDENTIAL This document is confidential. Do not disclose or use except as authorized. Downloaded From: https://jamanetwork.com/ on 09/24/2021 Phase II Study of Neoadjuvant FOLFIRINOX + Proton RT for Borderline Resectable Pancreatic Cancer Theodore S. Hong, MD 5/19/16 $JHQW V 5-Fluorouricil, Leucovorin calcium, Oxaliplatin, Irinotecan, Capecitabine, Proton or Photon Beam Irradiation, (no IND) )XQGLQJ6XSSRUW: )HGHUDO6KDUHRISURJUDPLQFRPHHDUQHGE\0DVVDFKXVHWWV*HQHUDO +RVSLWDORQ&&$3URWRQ7KHUDS\5HVHDUFKDQG7UHDWPHQW&HQWHU CONFIDENTIAL This document is confidential. Do not disclose or use except as authorized. Downloaded From: https://jamanetwork.com/ on 09/24/2021 Phase II Study of Neoadjuvant FOLFIRINOX with Short Course RT for Borderline Resectable Pancreatic Cancer Theodore S. Hong 5/19/16 3HULRSHUDWLYH)2/),5,12;ZLWK6KRUW&RXUVH5DGLDWLRQ7KHUDS\ LQ%RUGHUOLQH5HVHFWDEOHDQG+LJK5LVN&DQFHURIWKH3DQFUHDV SCHEMA Informed Consent and Registration Weeks 1-up to 20: FOLFIRINOX therapy, up to eight cycles Restaging CT after the first week of cycle 4 and the first week of the last cycle. A break in therapy of up to one week for restaging is allowed. At completion of At completion of FOLFIRINOX: FOLFIRINOX: Clearly Response or stable Resectable: disease but not clearly 1-4 weeks after completion of resectable: FOLFIRINOX: Proton or Photon RT with capecitabine OFF STUDY 825 mg/m2 bid x 10 days Follow for additional care as per treatment standard, resection outcome, secondary Surgery: pancreaticoduodenectomy or distal endpoints pancreatectomy 1-4 weeks after completion of CRT followed by 28-60 days recovery PRIMARY ENDPOINT: R0 resection Disease Progression noted at any point (restaging CT, clinical exam, or laparotomy): OFF STUDY R0, R1, R2 resections: Restaging CT Follow for secondary endpoints; care as per treatment standard. Additional chemotherapy may be given per physician discretion/patient tolerance. No Progression on restaging CT: Follow for secondary endpoints; care as per treatment standard Adjuvant chemotherapy per physician/patient tolerability CONFIDENTIAL This document is confidential. Do not disclose or use except as authorized. 3 Downloaded From: https://jamanetwork.com/ on 09/24/2021 Phase II Study of Neoadjuvant FOLFIRINOX with Short Course RT for Borderline Resectable Pancreatic Cancer Theodore S. Hong 5/19/16 7$%/(2)&217(176 1.1 Study Design ........................................................................................................................8 1.2 Primary Objective ................................................................................................................8 1.3 Secondary Objectives ...........................................................................................................8 %$&.*5281' 2.1 Study Agents ........................................................................................................................9 2.2 Disease Background...........................................................................................................16 (/,*,%,/,7<&5,7(5,$ 3.1 Inclusion Criteria: ..............................................................................................................30 3.2 Exclusion Criteria ............................................................................................................32 3.3 Inclusion of Women, Minorities and Other Underrepresented Populations ......................33 5(*,675$7,21352&('85(6 4.1 General Guidelines for DF/HCC and DF/PCC Institutions ...............................................33 4.2 Registration Process for DF/HCC and DF/PCC Institutions ...........................................34 75($70(173/$1 5.1 Pre-Treatment Criteria .......................................................................................................34 5.2 Agent Administration .........................................................................................................35 5.3 General Concomitant Medication and Supportive Care Guidelines: .................................41 5.4 Duration of Therapy ...........................................................................................................41 5.5 Duration of Follow Up .......................................................................................................41 5.6 Criteria for Removal from Study .......................................................................................42 (;3(&7('72;,&,7,(6$1''26,1*'(/$<602',),&$7,216 4 Downloaded From: https://jamanetwork.com/ on 09/24/2021 Phase II Study of Neoadjuvant FOLFIRINOX with Short Course RT for Borderline Resectable Pancreatic Cancer Theodore S. Hong 5/19/16 6.1 Anticipated Toxicities ........................................................................................................42 6.2 Toxicity Management ........................................................................................................44 6.3 Capecitabine and Proton Radiation .....................................................................................50 '58*)2508/$7,21$1'$'0,1,675$7,21 7.1 5-Fluorouracil (5-FU; fluorouracil; Adrucil" ) ..................................................................50 7.2 Leucovorin
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