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Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer (FOLFIRINOX)

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ClinicalTrials.gov Identifier: NCT01523457
Recruitment Status : Completed
First Posted : February 1, 2012
Results First Posted : August 30, 2017
Last Update Posted : August 30, 2017
Sponsor:
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date  ICMJE January 23, 2012
First Posted Date  ICMJE February 1, 2012
Results First Submitted Date  ICMJE September 1, 2016
Results First Posted Date  ICMJE August 30, 2017
Last Update Posted Date August 30, 2017
Study Start Date  ICMJE October 2011
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 28, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 31, 2012)
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.
Change History Complete list of historical versions of study NCT01523457 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 28, 2017)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2012)
  • Objective Response Rate [ Time Frame: 24 weeks ]
    Response will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 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 (Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011;364:1817-25.)
  • Rate of resection in patients with locally advanced unresectable disease [ Time Frame: 24 weeks ]
    The rate of surgical resection in the cohort of patients with locally advanced unresectable 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer
Official Title  ICMJE Phase II Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Pancreatic Cancer
  • Pancreatic Cancer
Intervention  ICMJE 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.

Study Arms  ICMJE
  • 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.
    Intervention: Drug: Folfirinox
  • 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.
    Intervention: Drug: Folfirinox
Publications * Stein SM, James ES, Deng Y, Cong X, Kortmansky JS, Li J, Staugaard C, Indukala D, Boustani AM, Patel V, Cha CH, Salem RR, Chang B, Hochster HS, Lacy J. Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer. Br J Cancer. 2016 Mar 29;114(7):737-43. doi: 10.1038/bjc.2016.45.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 28, 2017)
75
Original Estimated Enrollment  ICMJE
 (submitted: January 31, 2012)
67
Actual Study Completion Date  ICMJE December 2015
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01523457
Other Study ID Numbers  ICMJE 1108008901
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jill Lacy, MD Yale University
PRS Account Yale University
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP