Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01661088
Recruitment Status : Active, not recruiting
First Posted : August 9, 2012
Results First Posted : August 8, 2018
Last Update Posted : May 1, 2019
Sponsor:
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: FOLFIRINOX Radiation: Intensity-modulated radiotherapy (IMRT) Procedure: Surgical Exploration Phase 2

Detailed Description:
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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Neoadjuvant FOLFIRINOX and FDR-Gemcitabine With Concurrent IMRT in Patients With Borderline Resectable Pancreatic Cancer
Study Start Date : June 2011
Actual Primary Completion Date : August 10, 2017
Estimated Study Completion Date : August 2019

Resource links provided by the National Library of Medicine


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 metastatic disease will be offered surgical exploration.

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 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.


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 :
  1. The Percentage of Patients That Underwent an R0 Resection [ Time Frame: 6 months ]
    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.


Secondary Outcome Measures :
  1. Median Progression-free Survival Time [ Time Frame: up to 2 years ]
    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

  2. Median Overall Survival Time [ Time Frame: up to 2 years ]
    To estimate overall survival as a function of time from study enrollment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01661088


Locations
Layout table for location information
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan Rogel Cancer Center
Investigators
Layout table for investigator information
Principal Investigator: Mark Zalupski, MD University of Michigan Rogel Cancer Center
  Study Documents (Full-Text)

Documents provided by University of Michigan Rogel Cancer Center:

Layout table for additonal information
Responsible Party: University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier: NCT01661088     History of Changes
Other Study ID Numbers: UMCC 2011.007
HUM 47389 ( Other Identifier: University of Michigan IRBMED )
First Posted: August 9, 2012    Key Record Dates
Results First Posted: August 8, 2018
Last Update Posted: May 1, 2019
Last Verified: April 2019
Keywords provided by University of Michigan Rogel Cancer Center:
Neoadjuvant FOLFIRINOX
FDR-Gemcitabine
Concurrent
IMRT
Borderline Resectable Pancreatic Cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Pancreatic Diseases
Digestive System Diseases
Endocrine System Diseases
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs