Randomized Phase II Study of Weekly ABI-007 plus Gemcitabine or Simplified LV5FU2 as First-line Therapy in Patients with Metastatic Pancreatic Cancer.

INTERVENTION: Trade Name: Abraxane Pharmaceutical Form: Powder for suspension for injection INN or Proposed INN: PACLITAXEL CAS Number: 33069‐62‐4 Other descriptive name: ABI‐007 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 5‐ Trade Name: Gemcitabine Product Name: gemcitabine Product Code: L01BC05 Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: GEMCITABINE CAS Number: 95058‐81‐4 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 38‐ Trade Name: Levofolinate de calcium Product Name: Leucovorin Product Code: V03AF04 Pharmaceutical Form: Solution for infusion INN or Proposed INN: Folinic Acid CAS Number: 68538‐85‐2 Other descriptive name: LEVOLEUCOVORIN Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Trade Name: Fluorouracile Product Name: 5FU Product Code: L01BC02 Pharmaceutical Form: Solution for infusion INN or Proposed INN: FLUOROURACIL Other descriptive name: FLUOROURACIL Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 50‐ CONDITION: metastatic pancreatic cancer ; MedDRA version: 14.1 Level: LLT Classification code 10033605 Term: Pancreatic cancer metastatic System Organ Class: 100000004864 Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: Evaluation of Progression free survival Primary end point(s): Progression Free Survival (PFS) Secondary Objective: ‐ Tumor Response Rate according to RECIST v1.1; ‐ Overall Survival; ‐ Health related to Quality of Life (EORTC QLQ C‐30); ‐ Safety profile (NCI CTCAE v4.0); ‐ Duration of response,; ‐ Duration of disease control,; ‐ Prognostic and predictive value of SPARC expression when feasible in both arms, hENT1 and dCK expressions in arm 1, and TS expression in arm 2. Timepoint(s) of evaluation of this end point: time interval from randomization to the date of first documented disease progression or death from any cause, whichever occurs first. Alive patients without progression will be censored at the last tumor assessment, either during study treatment period or during follow‐up period. SECONDARY OUTCOME: Secondary end point(s): Tumor response; Overall survival; Time to Quality of Life (QoL) score deterioration for targeted dimensions Timepoint(s) of evaluation of this end point: Tumor response will be assessed every 2 months using RECIST version 1.1. ; Overall survival is defined as the time interval from randomization to the date of death from any cause. Alive patients will be censored at the last date known to be alive, either during study treatment period or during follow‐up period.; QoL will be assessed at D1 of each cycle. INCLUSION CRITERIA: 1. Signed and dated informed consent, and willing and able to comply with protocol requirements, 2. Histologically or cytologically proven adenocarcinoma of the pancreas, 3. Metastatic disease confirmed (stage IV), 4. No prior therapy for metastatic disease (in case of previous adjuvant therapy, interval from end of chemotherapy and relapse must be >12 months), 5. At least one measurable or evaluable lesion as assessed by CT‐scan or MRI (Magnetic Resonance Imaging) according to RECIST v1.1 guidelines, 6. Age =18 years, 7. ECOG Performance status (PS) 0‐2, 8. Hematological status: neutrophils (ANC) >1.5x109/L; platelets >100x109/L; haemoglobin =9g/dL, 9. Adequate renal function: serum creatinine level <150µM, 10. Adequate liver function: AST (SGOT) and ALT (SGPT) =2.5xULN (=5xULN in case of liver metastases) 11. Total bilirubin =1.5 x ULN, albumin =25g/L 12. Baseline evaluations performed before randomization: clinical and blood e