A prospective, multicenter, randomized, double-blind, placebo-controlled, 2-parallel group, Phase III study to compare efficacy and safety of masitinib at 9 mg/kg/day in combination with gemcitabine, to placebo in combination with gemcitabine, in treatment of patients with advanced/metastatic pancreatic cancer

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 352

Inclusion Criteria

1. Histologically or cytologically confirmed adenocarcinoma of the pancreas
2. Chemo naïve patient with advanced/metastatic disease
3. Documented decision justifying non eligibility for surgical resection. The documentation of the non eligibility for surgical resection will be reviewed by an independent committee.
4. Measurable tumor lesions with longest diameter = 20 mm using conventional techniques or = 10 mm with spiral CT scan according RECIST criteria
5. ECOG = 1
6. Patient with a BMI > 18 kg/m² and weighing at least 40kg
7. Patient with organ function as follows:
•Absolute neutrophil count (ANC) = 1.5 x 109/L
•Haemoglobin = 10 g/dL
•Platelets = 100 x 109/L
•AST/ALT = 2.5x ULN (= 5 x ULN in case of liver metastases)
•GammaGT < 3 x ULN (< 5 x ULN in case of liver metastases)
•Bilirubin = 1.5x ULN (= 3 x ULN in case of hepatic metastases)
•Creatinin clearance = 50 mL/min (Cockcroft and Gault formula)
•Albuminemia = 1 x LLN (32g/L)
•Urea = 2 x ULN
•Proteinuria < 30 mg/dL on the dipstick; in case of proteinuria = 30 mg/dL, 24-hour proteinuria should be < 1.5g/24 hours
8. Patient with life expectancy > 12 weeks
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Patient treated for a cancer other than pancreatic cancer within 5 years before enrollment, with the exception of basal cell carcinoma or cervical cancer in situ
2. Patient with, or with history, of central nervous system (CNS) metastasis
3. Patient with an abnormal cardiac function as defined as:
a.Medical history of myocardial infarction
b.Medical history of cardiac failure defined as a LVEF < 50% and/or a current treatment for cardiac failure,
c.Severe arrhythmia/conduction disorders, defined as severe ventricular arrhythmia; atrioventricular block at second or third level and/or left bundle branch block.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: During this study, an ancillary pharmacogenomic study will be performed in order to define predictive criteria of efficacy (all efficacy variables: survival and tumor assessment) from genomic data.<br>;Primary end point(s): Overall survival (OS). ;Timepoint(s) of evaluation of this end point: Analyses will be conducted after all patients will have been followed for 12 months (corresponding to 252 events);Main Objective: The objective is to compare efficacy and safety of masitinib at 9 mg/kg/day in combination with gemcitabine, to placebo in combination with gemcitabine, in treatment of patients with advanced/metastatic pancreatic cancer.<br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Tumor assessment:<br>· OS rate every 6 months<br>· Progression Free Survival (PFS).<br>· Time to Progression (TTP)<br>· Objective response rate (CR + PR) and control disease rate (CR + PR + SD) at week 24, 48<br>and 72<br>· Best response along study<br>· Level of serum CA 19-9 at week 24, 48 and 72