Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Gemcitabine

Oxaliplatin

Leucovorin

Fluorouracil

Irinotecan

Folfirinox

Patients will receive FOLFIRINOX x 6 followed by IMRT concurrent with fixed dose rate (FDR)-gemcitabine (1g/m\^2) on days 1, 8, 22, 29.

Intensity-modulated radiotherapy (IMRT): The prescribed dose was 50.0Gy in 2.0Gy per fraction.

Patients without metastatic disease will be offered surgical exploration.

Starting dose levels as following:

Oxaliplatin 85mg/m2 intravenously over 120 minutes on day 1. Irinotecan 180mg/m2 intravenously over 90 minutes on day 1. NOTE: patients homozygous for the UGT1A1 (TA)7 promoter allele will be treated at an initial lower dose 140mg/m2 (please see Section 6.3.a) Leucovorin 400mg/m2 intravenously over 90 minutes on day 1. 5FU 400mg/m2 as bolus intravenous injection following leucovorin on day 1. 5FU 2,400mg/m2 infused intravenously as a continuous infusion over 46 hours following the bolus 5FU, beginning on day 1.

FOLFIRINOX

Intensity-modulated radiotherapy (IMRT)

Patients without metastatic disease will be offered surgical exploration.

Surgical Exploration

Mark Zalupski, MD

The investigators hypothesize that the combination of the FOLFIRINOX regimen (a combination of 5-fluorouracil, irinotecan and oxaliplatin chemotherapy) to provide maximal systemic disease control and FDR-gemcitabine chemotherapy with concurrent IMRT (Radiation therapy) to address local disease, will achieve a significant improvement R0 resection (Radiation oncology repeat surgeries) rate in borderline resectable (surgical) pancreatic cancer and enhance disease free and overall survival in this patient population.

Gemcitabine has been the cornerstone of systemic therapy for pancreas cancer over this past decade. Recently, a combination of 5-fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) was reported to have significant efficacy in advanced pancreatic cancer. Preclinical data suggests synergy between irinotecan and 5FU as well as between oxaliplatin and 5FU. Results of a phase II trial in advanced disease were reported in 2005 demonstrating a 26% confirmed response rate and median overall survival of 10.2 months. A follow-up phase III trial comparing FOLFIRINOX with gemcitabine for patients \<75 years of age with advanced pancreatic cancer was presented at ASCO 2010 revealing improvement in PFS (6.4 vs 3.3 months, p=\<.0001) and improved disease control rate (CR+PR+SD) (70.2% vs 50.9%, p=.0003). The most notable result was an impressive improvement in median overall survival with FOLFIRINOX compared to gemcitabine (11.1vs 6.8 months, p-value = \<.0001, HR=.57). The main toxicity was grade 3/4 neutropenia (45.7% vs 18.7%, p=.0001) and increased risk of febrile neutropenia (5.4% vs 0.6%, p=.009)31.

A Study of Neoadjuvant FOLFIRINOX and FDR-Gemcitabine With Concurrent IMRT in Patients

A Phase II Study of Neoadjuvant FOLFIRINOX and FDR-Gemcitabine With Concurrent IMRT in Patients With Borderline Resectable Pancreatic Cancer

To determine the frequency of achieving an R0 resection using a neoadjuvant regimen of FOLFIRINOX followed by IMRT concurrent with fixed dose rate (FDR)-gemcitabine in patients with borderline resectable pancreatic cancer. R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed.

To estimate progression-free survival as a function of time from study enrollment. Progression is defined as at least a 20% increase in the LD (longest diameter) of the primary lesion or the appearance of one or more new lesions

To estimate overall survival as a function of time from study enrollment.

University of Michigan Rogel Cancer Center

Patients received FOLFIRINOX x 6 followed by IMRT concurrent with fixed dose rate (FDR)-gemcitabine (1g/m\^2) on days 1, 8, 22, 29.

Intensity-modulated radiotherapy (IMRT): The prescribed dose was 50.0Gy in 2.0Gy per fraction.

Patients without metastatic disease were offered surgical exploration.

Spots Global Cancer Trial Database for neoadjuvant folfirinox