French national multicentric phase III trial evaluating chemotherapy with Folfirinox or gemcitabine in locally advanced pancreatic carcinoma.

Comparative interventional prospective phase 3, randomized, open-label, multicentric trial comparing chemotherapy with Folfirinox to Gemcitabine in locally advanced pancreatic carcinoma.

Inclusion Criteria:

1. Histologically or cytologically confirmed adenocarcinoma of the pancreas

2. Proven unresectability after multidisciplinary discussion involving radiologist and a surgeon

3. Locally advanced (i.e.: no metastasis or suspicion of metastasis) and unresectable tumors: for example mesenteric or portal vein involvement, or > 180° encasement of the superior mesenteric artery, or celiac abutment (NCCN 2012 criteria)

4. Measurable tumor lesions with longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan according RECIST 1.1

5. WHO Performance status (PS) 0-1

6. Age ≥18 years

7. Patient with organ function as follows:

   • Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L
   • Hemoglobin ≥ 10 g/dL
   • Platelets (PTL) ≥ 75 x 10⁹/L
   • Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
   • Bilirubin ≤ 1.5 x ULN
   • Creatinine ≤ 2 x ULN
   • Albumin > 0.75 x lower limit of normal (LLN)
   • Urea ≤ 2 x ULN

8. Adequate vital functions

9. Patient of child-bearing potential (for female patient: study entry after a menstrual period and a negative pregnancy test) must agree to use medically acceptable methods of contraception during the study and for 4 months after the last intake of study treatment for women and for 6 months after for men.

10. Patient information and signed informed consent form

11. Public or private health insurance coverage

12. Uracilemia < 16 ng/ml

Exclusion Criteria:

1. Patient treated for a cancer other than pancreatic cancer within 5 years before enrolment, with the exception of basal cell carcinoma or in situ cervical cancer
2. Patient with metastasis or with history of metastasis
3. Patient with grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e. congestive heart failure, myocardial infarction within 6 months before baseline)
4. Major comorbidity, active infection (HIV or chronic hepatitis B or C) or uncontrolled diabetes that may preclude the delivery of the treatment
5. Pre-existing neuropathy (Grade ≥ 2), Gilbert's disease or genotype UGT1A1 * 28 / * 28
6. Pregnant woman
7. Fructose intolerance
8. Patients currently treated by warfarin
9. Persons deprived of liberty or under guardianship
10. Psychological condition, family-, sociological- or geographical situation potentially hampering compliance with the study protocol and the follow-up schedule

Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.

The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.

Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.