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Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer (FOLFIRINOX)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01523457
First Posted: February 1, 2012
Last Update Posted: August 30, 2017
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.
Information provided by (Responsible Party):
Yale University
  Purpose
The primary objective of this study was to determine the progression free survival in patients with metastatic pancreatic cancer and in patients with locally advanced unresectable non-metastatic pancreatic cancer treated with a dose-attenuated modification of folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX). Secondary endpoints included: determine objective response rate according to RECIST; determine overall survival; evaluate toxicity; determine rate of resection in locally advanced unresectable stratum; correlate time to progression, objective response, and overall survival with early changes in glucose metabolism using [18F]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scanning.

Condition Intervention Phase
Metastatic Pancreatic Cancer Pancreatic Cancer Drug: Folfirinox Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: 24 weeks ]
    The primary objective of this study is to determine the progression free survival in patients with metastatic pancreatic cancer and in patients with locally advanced unresectable non-metastatic pancreatic cancer treated with a dose-attenuated modification of FOLFIRINOX. Tumour response was determined according to RECIST 1.1 by independent radiology review.


Secondary Outcome Measures:
  • Objective Response Rate [ Time Frame: 24 weeks ]
    Response will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST 1.1 by independent radiology review) at 8 week intervals in patients with metastatic disease and in patients with locally advanced disease.

  • Overall Survival [ Time Frame: 24 weeks ]
    Overall survival will be determined in patients with metastatic disease and in patients with locally advanced disease.

  • Toxicity [ Time Frame: 24 weeks ]
    Toxicities will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) 4.0. Rates of grade 3 and 4 toxicities will be compared to historical controls. MPC and LAPC are combined because they were given the exact same medication. The study aimed to compare this dosage with historical dosage, so this comparison is the most appropriate.

  • Rate of Resection in Patients With Locally Advanced Disease [ Time Frame: 24 weeks ]
    The rate of surgical resection in the cohort of patients with locally advanced disease will be determined.

  • Correlate Time to Progression, Objective Response, and Overall Survival With Early Changes in Glucose Metabolism Using FDG-positron Emission Tomography (PET) Scanning [ Time Frame: 24 weeks ]
    The time to progression, objective response rate, and overall survival will be correlated with early changes in glucose metabolism using FDG-positron emission tomography (PET) scanning in patients with metastatic disease and locally advanced disease.


Enrollment: 75
Study Start Date: October 2011
Study Completion Date: December 2015
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MPC modified FOLFIRINOX
Patients with metastatic pancreatic cancer (MPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis.
Drug: Folfirinox
  • Oxaliplatin 85 mg/m2 IV infused over two hours, followed by
  • Leucovorin 400 mg/m2 IV over two hours
  • Irinotecan 135 mg/m2 IV over 90 minutes (concurrent with leucovorin during the last 90 min of the leucovorin infusion)
  • 5-FU 300mg/m2 IV bolus, then 2400 mg/m2 continuous IV infusion over 46 hours

FOLFIRINOX is a chemotherapy regimen. It is made up of the following four drugs:

FOL - folinic acid (leucovorin), a vitamin B derivative that modulates/potentiates/reduces the side effects of fluorouracil; F - fluorouracil (5-FU), a pyrimidine analog and antimetabolite which incorporates into the DNA molecule and stops DNA synthesis; IRIN - irinotecan (Camptosar), a topoisomerase inhibitor, which prevents DNA from uncoiling and duplicating; and OX - oxaliplatin (Eloxatin), a platinum-based antineoplastic agent, which inhibits DNA repair and/or DNA synthesis.

Experimental: LAPC modified FOLFIRINOX
Patients with locally advanced pancreatic cancer (LAPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis.
Drug: Folfirinox
  • Oxaliplatin 85 mg/m2 IV infused over two hours, followed by
  • Leucovorin 400 mg/m2 IV over two hours
  • Irinotecan 135 mg/m2 IV over 90 minutes (concurrent with leucovorin during the last 90 min of the leucovorin infusion)
  • 5-FU 300mg/m2 IV bolus, then 2400 mg/m2 continuous IV infusion over 46 hours

FOLFIRINOX is a chemotherapy regimen. It is made up of the following four drugs:

FOL - folinic acid (leucovorin), a vitamin B derivative that modulates/potentiates/reduces the side effects of fluorouracil; F - fluorouracil (5-FU), a pyrimidine analog and antimetabolite which incorporates into the DNA molecule and stops DNA synthesis; IRIN - irinotecan (Camptosar), a topoisomerase inhibitor, which prevents DNA from uncoiling and duplicating; and OX - oxaliplatin (Eloxatin), a platinum-based antineoplastic agent, which inhibits DNA repair and/or DNA synthesis.


Detailed Description:

A phase II open label single arm multi-institutional study at Yale's Smilow Cancer Hospital (New Haven, CT, USA), the Smilow Cancer Hospital Care Centers (regional community-based clinics), the VA Connecticut Healthcare System West Haven Campus (West Haven, CT, USA) and Bridgeport Hospital (Bridgeport, CT, USA). The primary objective of this study was to determine the PFS in patients with MPC and LAPC treated with a dose attenuated modification of FOLFIRINOX.

NOTE: Upon results reporting (2016), the registration record was reorganized to display MPC and LAPC groups in individual arms. The most meaningful comparison is between MPC/LAPC and historical controls. That is how results are reported in the published paper, see citations.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologic or cytologic documentation of pancreatic adenocarcinoma
  • Metastatic or locally advanced unresectable disease, including borderline unresectable disease
  • Patients with biliary or gastroduodenal obstruction must have drainage or surgical bypass prior to starting chemoradiation
  • Measurable or non-measurable assessable disease
  • No prior treatment (chemotherapy, biological therapy, or radiotherapy) for metastatic or non-metastatic locally advanced unresectable pancreatic cancer
  • 6 months since completion of any prior neoadjuvant or adjuvant therapy (chemotherapy or radiotherapy) for resected pancreatic cancer
  • No prior treatment with oxaliplatin or irinotecan
  • No prior treatment with fluoruouracil or capecitabine unless administered as a radiosensitizing drug during adjuvant/neoadjuvant chemoradiotherapy after/before resection of pancreatic cancer
  • Patients who received chemotherapy > 2 years ago for malignancies other than pancreatic cancer are eligible, provided that chemotherapy was completed > 2 years ago and there is no evidence of the second malignancy at the time of study entry
  • > 4 weeks since major surgery
  • No other concurrent anticancer therapy
  • ECOG Performance Status: 0-1
  • Age > 18
  • No other malignancy within past two years except basal cell carcinoma of the skin, cervical carcinoma in situ, or nonmetastatic prostate cancer
  • Paraffin block or slides must be available
  • Adequate organ function
  • No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
  • No > grade 1 sensory peripheral neuropathy
  • No uncontrolled seizure disorder, active neurological disease, or known CNS disease
  • No significant cardiac disease, including the following: unstable angina, New York Heart Association class II-IV congestive heart failure, myocardial infarction within six months prior to study enrollment
  • No history of chronic diarrhea
  • Not pregnant and not nursing
  • No other medical condition or reason that, in the opinion of the investigator, would preclude study participation
  • Laboratory parameters as follows: absolute neutrophil count ≥ 1,500/uL, platelet count ≥ 100,000/uL, hemoglobin ≥ 9 g,/dL, creatinine < 1.5 X ULN or estimated GFR > 30 ml/min, bilirubin < 1.5 X ULN, AST and ALT < 3 X ULN, negative pregnancy test in women of childbearing age
  Contacts and Locations
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): NCT01523457


Locations
United States, Connecticut
Smilow Cancer Center
New Haven, Connecticut, United States, 06510
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Jill Lacy, MD Yale University
  More Information

Publications:
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT01523457     History of Changes
Other Study ID Numbers: 1108008901
First Submitted: January 23, 2012
First Posted: February 1, 2012
Results First Submitted: September 1, 2016
Results First Posted: August 30, 2017
Last Update Posted: August 30, 2017
Last Verified: May 2017

Keywords provided by Yale University:
metastatic pancreatic cancer
locally advanced pancreatic cancer
FOLFIRINOX
phase II
progression free survival

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Oxaliplatin
Irinotecan
Leucovorin
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antidotes
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances