Efficacy of Gembrax Followed by Folfirinox Versus Folfirinox Alone in First Metastatic Line Pancreatic Cancer Patients

Inclusion Criteria:

1. Male or female aged 18 to 75 on the date the consent is signed.

2. Histologically or cytologically proven metastatic pancreatic adenocarcinoma. Thedefinitive diagnosis of pancreatic adenocarcinoma metastases will be made byintegrating the histopathological data in the context of the radiological data.

3. One or more metastatic lesion (s) measurable (Recist 1.1) by Thoraco-Abdomino-Pelvicscanner (or hepatic MRI and Thoraco-Abdomino-Pelvic scanner not injected, if thepatient is allergic to the product of contrast).

4. Previous treatment (including radiochemotherapy) for the non-metastatic diseaseauthorized if a delay ≥ 6 months between the last treatment and the recurrence isrespected.

5. WHO performance status ≤ 1

6. Uracilemia <16 ng / ml

7. Acceptable hematological assessment at inclusion (obtained within 14 days before thestart of treatment) defined by: • Neutrophils ≥ 2 × 109 / L; • Platelets ≥ 100,000 /mm3 (100 × 109 / L); • Hemoglobin ≥ 9 g / dl.

8. Acceptable renal and hepatic function at inclusion (obtained within 14 days beforethe start of treatment) defined by: • AST and ALT ≤ 2.5 x upper limit of the norm (ULN), unless liver metastases are present in this case AST and ALT ≤ 5 × ULN isallowed; • Total bilirubin ≤ 1.5 x ULN; • Serum creatinine within the norm limits orcalculated clearance ≥ 50ml / min for patients with a serum creatinine value aboveor below the norm values (clearance calculated by the CKD-EPI formula).

9. Calcemia AND magnesemia AND kalaemia ≥ LLN and ≤ 1.2 x ULN

10. If the patient is sexually active, he must agree to use contraception deemedadequate and appropriate by the investigator throughout the period of administrationof the study drug and up to 6 months after discontinuation of treatment for womenand for men.

11. Signature of consent before any procedure specific to the study.

12. Affiliated with the French national social security.

Exclusion Criteria:

1. Known brain metastasis.

2. Previous treatment with radiotherapy, surgery, chemotherapy or experimental therapyfor the treatment of metastatic disease.

3. Major surgery, other than diagnostic surgery (that is, surgery done to obtain adiagnostic biopsy without organ harvesting), within 4 weeks of day 1 of studytreatment.

4. Known Gilbert's syndrome or homozygous for know UGT1A1 * 28

5. Other concomitant cancer or history of cancer, except cervical cancer in situtreated, skin basal or squamous cell carcinoma, superficial bladder tumor (Ta, Tis,and T1) or a tumor with a good prognosis treated curatively without chemotherapy andwithout any sign of disease in the 3 years preceding inclusion.

6. Patients with high cardiovascular risk, including, but not limited to, coronarystent or myocardial infarction within the past 6 months.

7. Peripheral sensory neuropathy ≥ grade 2 at the time of inclusion.

8. ECG with a QTc interval greater than 450 ms for men and greater than 470 ms forwomen

9. Any other concomitant and unbalanced disease or serious disturbance that mayinterfere with the patient's participation in the study and his safety during thestudy (eg severe hepatic, renal, pulmonary, metabolic, or psychiatric disorders)

10. Allergy or intolerance to any study drug (gemcitabine, nab-paclitaxel, oxaliplatin,irinotecan, 5-FU) or any excipient (e.g., fructose) as described in the sections "contraindication or special warnings and precautions" or "prescribing information"of the summary of product characteristics indications.

11. Pregnant or breastfeeding women. Women of childbearing potential must have anegative pregnancy test (serum β-hCG) within 72 hours prior to inclusion.

12. Patients on vitamin K antagonists (e.g., Coumadin) (modifications to treatment maybe required prior to inclusion).

13. Treatment with brivudine within 4 weeks before or after treatment with 5-fluorouracil (due to a potentially fatal interaction).

14. Active and uncontrolled bacterial, viral, or fungal infections requiring systemictreatment.

15. Active HIV infection, known hepatitis B or C infection.

16. History of peripheral arterial disease (e.g., claudication, Buerger's disease),chronic inflammatory bowel disease or rectal disease, pulmonary fibrosis orinterstitial pneumonia.

17. Administration of a live attenuated vaccine within 10 days before inclusion and upto 6 months post-treatment.

18. Patient refusal or inability to comply with study procedures.

19. Inability to undergo follow-up for geographical, social, or psychological reasons.

20. Participation in another clinical trial involving an investigational product withinthe 30 days prior to inclusion.

21. Legal incapacity (patient under guardianship or guardianship).