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FOLFIRINOX for Unresectable Locally Advanced and Borderline Resectable Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT01688336
Recruitment Status : Terminated (Results unlikely to impact treatment patterns. Time to complete not justified.)
First Posted : September 19, 2012
Results First Posted : August 21, 2017
Last Update Posted : October 6, 2017
Sponsor:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE September 14, 2012
First Posted Date  ICMJE September 19, 2012
Results First Submitted Date  ICMJE July 21, 2017
Results First Posted Date  ICMJE August 21, 2017
Last Update Posted Date October 6, 2017
Study Start Date  ICMJE January 2012
Actual Primary Completion Date August 22, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 14, 2012)
Median Overall Survival (OS) of FOLFIRINOX in Patients With Unresectable Locally Advanced (ULA) Pancreatic Cancer [ Time Frame: Up to 3 years ]
All patients who receive at least Day 1 of FOLFIRINOX treatment will be evaluable and followed up for up to 3 years for the primary outcome of overall survival (OS).
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01688336 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2017)
  • Overall Survival for Borderline Resectable Patients [ Time Frame: Up to 3 years ]
    All patients who receive at least Day 1 of FOLFIRINOX treatment will be evaluable and followed up for up to 3 years for the outcome of overall survival (OS)
  • Progression Free Survival (PFS) [ Time Frame: the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years ]
    Progression free survival will be measured from D1 of treatment until evidence of tumor progression (including clinical deterioration related to the underlying pancreatic cancer, as assessed by the investigator) or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Patients that are lost to follow-up will be censored
  • Objective Response Rate [ Time Frame: Up to 3 years ]
    All patients who have received at least one cycle of treatment will be evaluated. Disease will be evaluated per Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) for target lesions and assessed by CT and/or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. Patients who drop out of the study prior to disease evaluation will not be evaluable for response unless the patient undergoes radiologic evaluation or their disease progresses clinically.
  • Disease Control Rate (DCR) [ Time Frame: Up to 3 years ]
    Disease control rate will be measured by the percentage of patients with responses (CR) and partial responses (PR) and stable disease (SD), per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI and/or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (POD); Complete Response (CR), Disappearance of all target lesions.
  • Rate of Resectability (RR) [ Time Frame: Up to 3 years ]
    Rate of resectability will be evaluated by determining the percentage of patients who were initially deemed to have ULA or borderline resectable (BR) disease and, following any period of treatment, were subsequently deemed to have resectable disease and undergo surgical resection. The denominator will reflect all patients with ULA or BR disease.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2012)
  • Overall Survival for Borderline Resectable Patients [ Time Frame: Up to 3 years ]
    All patients who receive at least Day 1 of FOLFIRINOX treatment will be evaluable and followed up for up to 3 years for the outcome of overall survival (OS)
  • Progression Free Survival (PFS) [ Time Frame: D1 of treatment until evidence of tumor progression ]
    Progression free survival will be measured from D1 of treatment until evidence of tumor progression (including clinical deterioration related to the underlying pancreatic cancer, as assessed by the investigator) or death from any cause. Patients that are lost to follow-up will be censored
  • Objective Response Rate [ Time Frame: Up to 3 years ]
    All patients who have received at least one cycle of treatment and have their disease reevaluated will be evaluable for assessment of objective response and will be followed for up to 3 years for survival. Disease will be evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) every eight weeks and at the time of disease progression by the same modality as the baseline evaluation: CT abdomen and chest (preferable) or MRI abdomen and CT chest. Objective response rate will be measured by the number of complete responses (CR) and partial responses (PR), as determined by RECIST 1.1 criteria. Patients who drop out of the study prior to disease evaluation will not be evaluable for response unless the patient undergoes radiologic evaluation or their disease progresses clinically.
  • Disease Control Rate (DCR) [ Time Frame: Up to 3 years ]
    Disease control rate will be measured by the rate of rate of radiographic complete responses (CR) and partial responses (PR) and stable disease (SD), as determined by RECIST 1.1 criteria.
  • Rate of Resectability (RR) [ Time Frame: Up to 3 years ]
    Rate of resectability will be evaluated by determining the number of patients who were initially deemed to have ULA or BR disease and, following any period of treatment, were subsequently deemed to have resectable disease and undergo surgical resection. The denominator will reflect all patients with ULA or BR disease.
Current Other Pre-specified Outcome Measures
 (submitted: September 14, 2012)
Correlation of Tumor Markers (Ca19-9, CEA) With Outcomes (RR, DCR, PFS, and OS). [ Time Frame: Up to 3 years ]
Tumor markers (Ca19-9, CEA) will be measured at baseline, every eight weeks and at end of treatment, and will be correlated with outcomes resectability response (RR),disease control rate (DCR), progression free survival (PFS) and overall survival (OS).
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE FOLFIRINOX for Unresectable Locally Advanced and Borderline Resectable Pancreatic Cancer
Official Title  ICMJE Phase II Single Arm Clinical Trial of FOLFIRINOX for Unresectable Locally Advanced and Borderline Resectable Pancreatic Cancer
Brief Summary This single arm, multi-center phase II clinical trial will assess the safety and efficacy of FOLFIRINOX in the first-line setting in patients with unresectable locally advanced (ULA) and borderline resectable (BR) pancreatic cancer.
Detailed Description

FOLFIRINOX regimen was recently presented at an international oncology meeting and represents a new standard in the treatment of metastatic pancreatic cancer for selected patients. With improved overall survival (OS) and response rates (RR) in the metastatic setting, we hypothesize that in patients with less tumor burden, this regimen will be safe and well tolerated, improve OS, progression free survival (PFS), and RR, and improve resectability rates, as compared to historical data from standard single agent gemcitabine therapy for unresectable locally advanced (ULA) patients and standard radiation with concurrent 5 fluorouracil (5FU) chemotherapy for borderline resectable (BR) patients. While both ULA and BR patients will be eligible for the present study, our primary objective concerns ULA patients, and we plan to enroll 45 patients in this group.

Patients meeting eligibility criteria will be consented and treated with FOLFIRINOX every 2 weeks (1 cycle = 4 weeks = 2 treatments). Patients will undergo repeat imaging (CT or MRI) every 2 cycles and reassessed for resectability of the tumor. All patients that are not able to undergo surgical resection, due to insufficient down-staging or patient preference, will continue on protocol-based therapy until disease progression, unacceptable toxicity, study withdrawal, or death.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Cancer
Intervention  ICMJE Drug: FOLFIRINOX

FOLFIRINOX will be given intravenously on Days 1, 15, and 28 of each 28 day cycle. Drugs are given in combination in this order:

  • Oxaliplatin (85 mg/m2)
  • Leucovorin (400mg/ m2)
  • Irinotecan (180 mg/m2)
  • 5FU (400mg/m2)bolus then 2400 mg/m2 over 46 hours
Other Names:
  • FOLFIRINOX is a chemotherapy regimen comprised of the following drugs, given in combination
  • -Oxaliplatin
  • -Leucovorin
  • -Irinotecan
  • -5FU
Study Arms  ICMJE Experimental: FOLFIRINOX
FOLFIRINOX given to all subjects
Intervention: Drug: FOLFIRINOX
Publications * Not Provided

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: February 10, 2017)
9
Original Estimated Enrollment  ICMJE
 (submitted: September 14, 2012)
45
Actual Study Completion Date  ICMJE November 22, 2016
Actual Primary Completion Date August 22, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Biopsy confirmed adenocarcinoma of the pancreas.
  • Measurable or non-measurable but evaluable (as determined by Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1]) unresectable locally advanced (ULA) or borderline resectable (BR) disease that is not amenable to curative intent therapy. Baseline CT abdomen and chest (or MRI abdomen) within 28 days prior to initiation of FOLFIRINOX is required.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • No prior chemotherapy or chemoradiotherapy for pancreatic cancer.
  • Age ≥ 18 years of age.
  • Laboratory requirements at study entry:

    • Hemoglobin ≥ 10 g/dL (transfusions are acceptable)
    • absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    • Platelets ≥ 100 x 109/L
    • Creatinine ≤ 1.5 x upper limit of normal (ULN), or creatinine clearance ≥ 50 mL/min (estimated by Cockcroft-Gault or measured)
    • Total bilirubin ≤ 1.5 x ULN
    • aspartate aminotransferase/Alanine Aminotransferase (AST/ALT) ≤ 3 x ULN
    • Gamma-Glutamyl Transferase (GGT) ≤ 5 x ULN
  • Life expectancy of at least 6 months.
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test performed within 14 days prior to initiation of FOLFIRINOX.
  • WOCBP and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and 8 weeks after the end of treatment.
  • Before patient registration, written informed consent must be given.

Exclusion Criteria:

  • Local recurrence or resectable recurrence of pancreatic cancer.
  • Other malignancies within the past 3 years except for adequately treated cervical or vulvar carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated >3 years prior to entry is permitted.
  • Hypersensitivity to 5FU, oxaliplatin or other platinum agent, or irinotecan or to their excipients. Known dihydropyrimidine dehydrogenase (DPD) enzyme deficiency.
  • Participation in any investigational drug study within 4 weeks preceding the start of study treatment. Patients are not permitted to participate in another investigational drug study while being treated on this protocol.
  • Cardiac disease: Congestive heart failure symptoms > class II New York Heart Association (NYHA). Unstable angina (anginal symptoms at rest) or new onset angina beginning within the last 3 months. Myocardial infarction within the past 6 months. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
  • History of or suspected Gilbert's Disease (baseline testing not required).
  • Baseline peripheral neuropathy/paresthesia grade ≥ 1.
  • Active hepatitis B, unless patient has been on stable meds for at least 2 months (baseline testing not required).
  • Active clinically serious infections (> grade 2).
  • Any other hemorrhage/bleeding event > CTCAE Grade 3 within the 12 weeks prior to the first dose FOLFIRINOX.
  • Evidence or history of bleeding diathesis or coagulopathy. Note: If therapeutic anticoagulation required, the investigator is encouraged to switch patient to (or maintain on) low molecular weight heparin during the trial.
  • Major surgery, open biopsy or significant traumatic injury within 8 weeks of first study drug. A core pancreatic or liver biopsy does not preclude the patient from the study.
  • Unable or unwilling to discontinue use of ketoconazole or St John's wort. Use of CYP3A4 enzyme-inducing drugs and strong CYP3A4 inhibitors is discouraged, but not contraindicated.
  • Active drug or alcohol abuse.
  • Pregnant or lactating women.
  • Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
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 NCT01688336
Other Study ID Numbers  ICMJE LCCC 1105
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party UNC Lineberger Comprehensive Cancer Center
Study Sponsor  ICMJE UNC Lineberger Comprehensive Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Autumn J McRee, MD University of North Carolina
PRS Account UNC Lineberger Comprehensive Cancer Center
Verification Date September 2017

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