Phase 2 Evaluation of Multi-modality Algorithm for Non-metastatic Adenocarcinoma of Pancreas or Ampulla

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase 2 Evaluation of a Community-Based Multi-modality Management Algorithm for Clinically Non-metastatic Ductal Adenocarcinoma of the Exocrine Pancreas or Ampulla

Conditions
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Ductal Adenocarcinoma of Pancreas, Adenocarcinoma of Ampulla

Intervention / Treatment
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* Drug: Gemcitabine and nanoparticle albumin bound paclitaxel
* Drug: 5-fluorouracil and irinotecan
* Radiation: Preoperative chemoradiation
* Procedure: Definitive resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic proof of adenocarcinoma consistent with ductal carcinoma of pancreas or ampulla, with no evidence of metastatic disease by clinical exam or cross-sectional imaging. Fitness for chemotherapy in judgement of treating physician Bilirubin < 4 (any means of biliary drainage acceptable) Exclusion Criteria: Medical or mental illness precluding provision of informed consent Pregnancy Active infection for which neutropenia would pose high risk of mortality

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Resectable, Low Risk<br>Systemic chemotherapy followed by definitive surgery without pre-operative or post-operative radiotherapy. | Drug: Gemcitabine and nanoparticle albumin bound paclitaxel<br>* Gemcitabine and nab-paclitaxel given every 14 days x 4 cycles<br>* Other names: Gem/Abraxane, Gemcitabine/nab-paclitaxel;Procedure: Definitive resection<br>* Definitive surgical resection of primary tumor<br>* Other names: pancreaticoduodenectomy, Whipple procedure;|
| Experimental: Locally Advanced<br>Systemic chemotherapy followed by chemoradiation, followed by definitive surgery | Drug: Gemcitabine and nanoparticle albumin bound paclitaxel<br>* Gemcitabine and nab-paclitaxel given every 14 days x 4 cycles<br>* Other names: Gem/Abraxane, Gemcitabine/nab-paclitaxel;Drug: 5-fluorouracil and irinotecan<br>* FOLFIRI.3 given every 14 days x 4 cycles<br>* Other names: FOLFIRI.3, FOLFIRI-3;Radiation: Preoperative chemoradiation<br>* Pre-operative chemoradiation to 40 Gy in 20 fractions<br>Procedure: Definitive resection<br>* Definitive surgical resection of primary tumor<br>* Other names: pancreaticoduodenectomy, Whipple procedure;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse Free Survival | Percentage of patients alive and free of detectable disease 1 yr from start of treatment | 1 yr form onset of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R-0 Rate | Rate of patients having surgery who have negative surgical margins (i.e. R-0 resection) | Time of surgery | 
| Overall Survival | Time to death from any cause measured from start of treatment | Up to 3 years from registration |