Regional Chemotherapy in Locally Advanced Pancreatic Cancer: RECLAP Trial

Background: * Pancreatic cancer is the fourth leading cause of cancer death in the United States. * Surgery offers the only chance at cure; however, less than 20% of patients are considered resectable at initial presentation. * A common reason for being classified as unresectable is loco-regional advanced disease. * Several phase I studies of regional administration of chemotherapy have proven safe. * The main advantage of pancreatic cancer targeted arterial perfusion of Gemcitabine is achievement of higher local bio-available active drug levels at the tumor bed. * The Regional Chemotherapy in Locally Advanced Pancreatic Cancer (RECLAP) trial is a phase I trial offering highly selective 24-hour intra-arterial administration of Gemcitabine via a subcutaneous port for patients with unresectable locally-advanced pancreatic cancer. Objectives: Primary Objective: * To evaluate feasibility and toxicity of intra-arterial gemcitabine therapy (dose limiting toxicity (DLT)). * To establish the maximum tolerated dose (MTD) Secondary Objectives: * To evaluate response rate using Response Evaluation Criteria in Solid Tumors (RECIST), positron emission tomography (PET), magnetic resonance imaging (MRI) and computed tomography (CT) perfusion criteria (European Association for the Study of the Liver (EASL)) * To determine progression free and overall survival. * To evaluate the conversion rate from unresectable or borderline resectable to potentially resectable pancreatic cancer. * To determine progression-free and overall survival. * To analyze potential selection criteria to be used in future studies for patients who present with marginally unresectable or unresectable locally-advanced pancreatic cancer that might benefit from this approach. Eligibility: * Unresectable locally-advanced pancreatic cancer. * 18 years old or greater with an Eastern Cooperative Oncology Group (ECOG) 0-2 * Laboratory and physical examination parameters within acceptable limits by standard of practice guidelines prior to surgery or chemotherapy. * No extra-pancreatic disease except regional lymph nodes. Design: * This is a dose escalation phase-I study. * Patients considered unresectable due to locally-advanced pancreatic cancer will receive selective arterial perfusion of gemcitabine over 24 hours via a subcutaneous indwelling port. * Treatment will be given on Days 1 and 14. One cycle = 4 weeks for up to six cycles. * Three to six patients will be enrolled per dose cohort. * 18 to 36 patients in 7 cohorts will be accrued plus 6 more patients at the maximum tolerated dose (MTD over 36 months. Patients will be evaluated every 2 cycles (8 weeks). Upon progression patients will be taken off study. If no progressive disease (PD), patients will continue up to 6 cycles. * Chemotherapy na(SqrRoot) ve patients and patients who received previously chemotherapy including gemcitabine will be allowed, as this mode of administration has better bioavailability, offer potential for better biological effect and less systemic toxicity profiles.