Studying Chemotherapy With or Without Panitumumab for Unresectable, Locally Advanced, or Metastatic Pancreatic Cancer Without KRAS Mutations

This phase III trial compares the effect of adding panitumumab to standard chemotherapy (with nanoliposomal Irinotecan, leucovorin, and 5-fluorouracil \[5-FU\] or irinotecan, leucovorin, and 5-FU or nab-paclitaxel and gemcitabine) versus standard chemotherapy alone in treating patients with KRAS wild type (WT) pancreatic ductal adenocarcinoma that cannot be removed by sugery (unresectable) or that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Panitumumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Chemotherapy drugs, such as nanoliposomal irinotecan, leucovorin, 5-FU, irinotecan, nab-paclitaxel and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding panitumumab to standard chemotherapy may be effective in treating patients with unresectable, locally advanced, or metastatic KRAS WT pancreatic ductal adenocarcinoma.

PRIMARY OBJECTIVE: I. To compare overall survival (OS) between participants with locally advanced or metastatic KRAS wild type (WT) pancreatic ductal adenocarcinoma (PDA) randomized to panitumumab plus second-line cytotoxic chemotherapy (5FU- or gemcitabine-based) versus chemotherapy alone. SECONDARY OBJECTIVES: I. To compare progression-free survival (PFS) between treatment arms. II. To compare the overall response rate (ORR) (ORR, including confirmed and unconfirmed, complete and partial response according to Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 criteria) between treatment arms in participants with measurable disease. III. To compare disease control rate (DCR) (DCR, defined as ORR + stable disease rate \[SD\]) between treatment arms in participants with measurable disease. IV. To evaluate the frequency and severity of toxicity within each treatment arm. V. To compare duration of response (DoR) between treatment arms in participants with measurable disease. ADDITIONAL OBJECTIVES: I. To compare OS and PFS between treatment arms in the subgroup of participants with MAPK negative cancers, that is, cancers without any known mitogen-activated protein kinase (MAPK) pathway molecular alterations (type 1 or 2 BRAF mutations; BRAF, NRG1, ROS1, FGFR1-3 and RAF1 fusions; EGFR, KRAS, and FGFR1-3 amplification). II. To compare ORR in participants with MAPK negative cancers between treatment arms in participants with measurable disease. PATIENT-REPORTED OUTCOMES COMMON TERMINOLOGY CRITIERIA FOR ADVERSE EVENTS (CTCAE) OBJECTIVES: I. To compare health-related quality of life (QOL) by treatment arm at 8 weeks after randomization, measured by the Functional Assessment of Cancer Therapy - General (FACT-G) total score. II. To compare the impact of treatment toxicity by treatment arm at 8 weeks after randomization, measured by the Functional Assessment of Chronic Illness Therapy (FACIT) Item GP5. III. To compare changes from baseline in QOL and impact of treatment toxicity between treatment arms using FACT-G total score and FACIT Item GP5 to 24 weeks after randomization. IV. To assess patient-reported symptoms by treatment arm using selected patient reported outcome (PRO)-CTCAE items including gastrointestinal, dermatologic, and constitutional symptoms of pain and fatigue. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive panitumumab intravenously (IV) over 30-90 minutes on days 1 and 15. Patients also receive either nanoliposomal irinotecan IV over 90 minutes on days 1 and 15, leucovorin IV over 30 minutes on days 1 and 15, and 5-FU IV over 46 hours on days 1-3 and 15-17 or irinotecan IV over 90 minutes, leucovorin IV over 90-120 minutes on days 1 and 15, 5-FU IV bolus over 5-15 minutes on days 1 and 15 and 5FU IV continuous over 46 hours on days 1-3 and 15-17 or nab-paclitaxel IV over 30 minutes, and gemcitabine IV over 30 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan and blood sample collection throughout the study. ARM B: Patients receive either nanoliposomal irinotecan IV over 90 minutes on days 1 and 15, leucovorin IV over 30 minutes on days 1 and 15, and 5-FU IV over 46 hours on days 1-3 and 15-17 or irinotecan IV over 90 minutes, leucovorin IV over 90-120 minutes on days 1 and 15, 5-FU IV bolus over 5-15 minutes on days 1 and 15 and 5FU IV continuous over 46 hours on days 1-3 and 15-17 or nab-paclitaxel IV over 30 minutes, and gemcitabine IV over 30 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and blood sample collection throughout the study. After completion of study treatment, patients are followed up for up to 3 years post randomization.