Accepting New Patients
This is a randomized phase II study to evaluate 18-month overall survival rate in patients with borderline resectable cancer of the head of the pancreas using one of the treatment regimens. Eastern Cooperative Oncology Group Performance Status 0 vs 1 is a stratification factor. The primary and secondary objectives are described below.
To evaluate and estimate 18 months overall survival (OS) rate of patients with borderline resectable PDAC receiving neoadjuvant therapy consisting of one of the following regimens prior to intended surgical resection and adjuvant therapy with 4 cycles of FOLFOX:Arm 1: 8 cycles of systemic FOLFIRINOX, and/or Arm 2: 7 cycles of systemic FOLFIRINOX followed by hypofractionated radiation therapy
Secondary Objectives:To evaluate and estimate the R0 resection rates in patients receiving each of the two multimodality treatment regimens. To evaluate and estimate the event-free survival in patients receiving each of the two multimodality treatment regimens. To evaluate and estimate the pathologic compete response (pCR) rates in patients receiving each of the two multimodality treatment regimens To assess the adverse events (AE) profile and safety of each treatment arm.
Patients will be followed up to 5 years post-registration.
Pre-Registration Eligibility Criteria:
Documentation of Disease:Pathology: Cytologic or histologic proof of adenocarcinoma of the pancreatic head or uncinate process. Diagnosis should be verified by local pathologist.
TNM Stage: TX, T1-4N0-1orNxM0*M1 disease includes spread to distant lymph nodes, organs, and ascites
Criteria for borderline resectable disease: Local radiographic reading must be consistent with borderline resectable cancer of the pancreatic head as defined by intergroup radiographic criteria and must meet any one or more of the following on CT/MRI:An interface is present between the primary tumor and the superior mesenteric vein or portal vein and measures ≥ 180° of the circumference of the vessel wall Short-segment occlusion of the SMV-PV is present with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction Short segment interface (of any degree) is present between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and reconstruction An interface is present between the tumor and superior mesenteric artery or celiac axis measuring < 180° of the circumference of the vessel wall Patients with less extensive disease than the above four (4) criteria are considered potentially resectable and are NOT eligible. Patients with more extensive disease than the above 4 criteria are considered locally advanced and are NOT eligible. In addition patients with the following are considered locally advanced and are NOT eligible: Any interface between the tumor and the aorta. See the protocol for additional clarification and definitions of less and more extensive disease.
Registration Eligibility Criteria:Disease Status - Confirmation of radiographic stage as borderline resectable disease by real-time Alliance central radiographic review
Prior TreatmentNo prior chemotherapy or radiation for pancreatic cancer No definitive resection of pancreatic cancer
Concomitant MedicationsChronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study. See the protocol for more information. Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment. See the protocol for more information.
Medical HistoryNo grade ≥ 2 neuropathy No known Gilbert's Syndrome or known homozygosity for UGAT1A1*28 polymorphism No uncontrolled gastric ulcer disease (Grade 3 gastric ulcer disease) within 28 days of registration Pregnancy and Nursing Status - Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done ≤ 7 days prior to registration is required. Age ≥ 18 years ECOG Performance Status 0 or 1
Required Initial Laboratory Values:Absolute Neutrophil Count (ANC) ≥ 1,500/mm3 Platelet Count ≥ 100,000/mm3 Creatinine ≤ 1.5 x upper limit of normal (ULN) or Calc. Creatinine Clearance > 45 mL/min Total Bilirubin ≤ 2.0 mg/dL AST / ALT ≤ 2.5 x ULN