Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer
Condition: Metastatic Pancreatic Cancer; Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: Folfirinox
Intervention description: 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.
Intervention MeSH terms: Folfirinox
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 75.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: metastatic pancreatic cancer; locally advanced pancreatic cancer; FOLFIRINOX; phase II; progression free survival

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.
    

Eligibility 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