Conditions: Ductal Adenocarcinoma of Pancreas Adenocarcinoma of Ampulla
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 11
Healthy volunteers: no

Brief summary:
Patients diagnosed with pancreatic cancer without clinically detectable metastatic disease will be treated with standardized systemic chemotherapy, followed by chemoradiation, and then surgical resection for those with resectable or borderline resectable disease. The primary endpoint is disease-free survival at 1 yr from initiation of treatment.

Detailed description:
Patients with ductal adenocarcinoma of the pancreas (or ampulla) that have received no prior therapy and have no clinically detectable metastatic disease will be enrolled. Management will be driven by resectability status as defined by the American College of Surgeons. All patients will be defined at entry as Resectable, Borderline Resectable or Locally Advanced (Unresectable).

All patients will be treated initially with gemcitabine and nanoparticle albumin bound paclitaxel (nab-paclitaxel) every 14 days for 4 cycles. Patients classified as Resectable, who have CA19-9 below 180 and CA-125 below 30 will then proceed to resection. All other patients will get 5-fluorouracil as 46 hr infusion given with leucovorin and irinotecan (FOLFIRI-3) every 14 days x 4 cycles.

All patients without progression will then receive chemoradiation consisting of external beam radiotherapy (40 Gy in 20 fractions given over 4 weeks). During radiation all patients will receive radiosensitizing radiotherapy as: 5-fluorouracil at 225 mg/m2 5 days per week, Mitomycin-C at 3 mg.m2 on d1, 8, 15 \& 22; Cisplatin at 10 mg/m2 on d2, 9, 16, 23 and unfractionated heparin at 6,000 units/m2 daily in divided doses from day 1 to day 28.

After approximately 4 weeks to recover from chemoradiation, all patients with Resectable or Borderline Resectable disease will undergo definitive surgery.

Adjuvant therapy with FOLFIR-3 for an additional 6 cycles will be offered to all patients post-operatively.

Patients will then be actively followed every 3 to 6 months in keeping with National Comprehensive Cancer Network (NCCN) guidelines for 2 yrs, and then followed for recurrence, late toxicity and vital status every 6 months through 5 years.

Arms:
arm 1: Systemic chemotherapy followed by definitive surgery without pre-operative or post-operative radiotherapy. arm 2: Systemic chemotherapy followed by chemoradiation, followed by definitive surgery

Interventions: intervention 1: Gemcitabine and nanoparticle albumin bound paclitaxel intervention 2: 5-fluorouracil and irinotecan intervention 3: Preoperative chemoradiation intervention 4: Definitive resection
Intervention descriptions: intervention 1: Gemcitabine and nab-paclitaxel given every 14 days x 4 cycles intervention 2: FOLFIRI.3 given every 14 days x 4 cycles intervention 3: Pre-operative chemoradiation to 40 Gy in 20 fractions intervention 4: Definitive surgical resection of primary tumor

Protocol document: