A Study Of Neoadjuvant FOLFIRINOX And FDR-Gemcitabine With Concurrent IMRT In Patients

Study Overview

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

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.

Pancreatic Cancer

DRUG: FOLFIRINOX
RADIATION: Intensity-modulated radiotherapy (IMRT)
PROCEDURE: Surgical Exploration

UMCC 2011.007
HUM 47389 (OTHER Identifier) (OTHER: University of Michigan IRBMED)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2012-07-24	Results First Submitted 2018-06-26	Last Update Submitted that met QC Criteria 2019-10-29
First Submitted that Met QC Criteria 2012-08-08	Results First Submitted that Met QC Criteria 2018-08-06	Last Update Posted (ACTUAL) 2019-11-13
First Posted (ACTUAL) 2012-08-09	Results First Posted 2018-08-08	Last Verified 2019-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Study Treatment 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 metast	DRUG: FOLFIRINOX 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 RADIATION: Intensity-modulated radiotherapy (IMRT) 50.0Gy in 2.0Gy per fraction PROCEDURE: Surgical Exploration Patients without metastatic disease will be offered surgical exploration.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Study Treatment

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 metast

DRUG: FOLFIRINOX

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

RADIATION: Intensity-modulated radiotherapy (IMRT)

50.0Gy in 2.0Gy per fraction

PROCEDURE: Surgical Exploration

Patients without metastatic disease will be offered surgical exploration.

Primary Outcome Measures	Measure Description	Time Frame
The Percentage of Patients That Underwent an R0 Resection	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.	6 months

Secondary Outcome Measures	Measure Description	Time Frame
Median Progression-free Survival Time	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	up to 2 years
Median Overall Survival Time	To estimate overall survival as a function of time from study enrollment.	up to 2 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Patients must have cytologic or histologic confirmation of carcinoma arising in the pancreas.
Patients must be deemed to have borderline resectable disease with no radiologic evidence of distant metastatic disease prior to registration.
Specifically, patients must have at least one designation of borderline resectable and no designation of unresectable disease.
Patients must have a life expectancy of at least 12 weeks, a Zubrod performance status of < 1 and be willing and medically able to undergo surgical resection.
Patients must have adequate organ function defined as follows: absolute neutrophil count of > 1500/mm3, platelets > 100,000/mm3, serum Cr < 1.5 mg/dl, total bilirubin < 2.0 mg/dl with relief of biliary obstruction if present (PTC tube or endobiliary stent).
Patients must be free of other active systemic malignancy, ongoing infection, or any other serious uncontrolled, concomitant systemic disorders or psychiatric condition that would interfere with the safe delivery of protocol therapy.
Patients of reproductive potential must agree to use an effective contraceptive method during participation in this trial due to the unacceptable teratogenic toxicity of abdominal radiation and cytotoxic chemotherapy.
Patients must be aware of the investigational nature of the therapy and provide written informed consent.

Patients with neuroendocrine tumors are excluded.
Active systemic malignancy, ongoing infection, or any other serious uncontrolled, concomitant systemic disorders or psychiatric condition that would interfere with the safe delivery of protocol therapy.
Patients with preexisting peripheral neuropathy > grade 2 are ineligible
Pregnant or nursing women are ineligible.
Patients must have no history of previous chemotherapy for pancreatic cancer or any abdominal radiation therapy.
Patients may not have used any investigational agent within 4 weeks prior to enrollment into the study.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Mark Zalupski, MD, University of Michigan Rogel Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Tran NH, Sahai V, Griffith KA, Nathan H, Kaza R, Cuneo KC, Shi J, Kim E, Sonnenday CJ, Cho CS, Lawrence TS, Zalupski MM. Phase 2 Trial of Neoadjuvant FOLFIRINOX and Intensity Modulated Radiation Therapy Concurrent With Fixed-Dose Rate-Gemcitabine in Patients With Borderline Resectable Pancreatic Cancer. Int J Radiat Oncol Biol Phys. 2020 Jan 1;106(1):124-133. doi: 10.1016/j.ijrobp.2019.08.057. Epub 2019 Sep 5.

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