Masitinib in Combination With Gemcitabine for Treatment of Patients With Advanced/Metastatic Pancreatic Cancer

Study Overview
=================
Brief Summary
-----------------
The objective of this study is to compare the efficacy and safety of masitinib in combination with gemcitabine to placebo in combination with gemcitabine in patients with advanced/metastatic pancreatic cancer.

Detailed Description
-----------------
Human pancreatic cancer overexpresses a number of important tyrosine kinase (TK) growth factors receptors and ligands, including expression of both PDGF and PDGF receptors. Drugs that can selectively inhibit TKs are likely to be of benefit in pancreatic cancer. Masitinib is a TK inhibitor, selectively and effectively inhibiting c-Kit (mast cell growth factor receptor), PDGF receptor, FGF receptor and to a lower extent the FAK kinases. Pre-clinical and clinical studies have shown that masitinib can reverse resistance of pancreatic tumor cell lines to gemcitabine. Based on pre-clinical and phase 2 clinical studies, masitinib can be considered as a good candidate to use in combination with gemcitabine in the treatment of pancreatic cancer.

Official Title
-----------------
A Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled, 2-parallel Group, Phase III Study to Compare Efficacy and Safety of Masitinib 9 mg/kg/Day in Combination With Gemcitabine Compared to Placebo in Combination With Gemcitabine in Treatment of Patients With Advanced/Metastatic Pancreatic Cancer

Conditions
-----------------
Pancreatic Cancer

Intervention / Treatment
-----------------
* Drug: Masitinib
* Drug: Placebo
* Drug: Gemcitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
Main Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the pancreas Chemo naïve patients with advanced/metastatic disease Documented decision justifying non eligibility for surgical resection. The documentation of the non eligibility for surgical resection will be reviewed by an independent committee. Men and women, age >18 years Men and women of childbearing potential (entering the study after a confirmed menstrual period and who have a negative pregnancy test), must agree to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake. Patient should be able and willing to comply with study visits and procedures as per protocol. Patient should understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures performed. Main Exclusion Criteria: Patient treated for a cancer other than pancreatic cancer within 5 years before enrollment, with the exception of basal cell carcinoma or in situ cervical cancer Any condition that the physician judges could be detrimental to subjects participating in this study; including any clinically important deviations from normal clinical laboratory values or concurrent medical events Previous treatment Any anti-tumor therapy (any chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy) within 6 months prior to baseline Treatment with any investigational agent within 4 weeks prior to baseline

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Masitinib & gemcitabine<br>Participants receive masitinib (9 mg/kg/day), given orally twice daily, plus gemcitabine at 1000mg/m2 by intravenous infusion during 30 minutes, once every 7 days, for up to 7 weeks, followed by a week of rest. Subsequent cycles should consist of an IV infusion, once every 7 days, for 3 consecutive weeks out of every 4 weeks, until disease progression, death, limiting toxicity or patient consent withdrawal. | Drug: Masitinib<br>* Masitinib at 9 mg/kg/day given orally twice daily<br>* Other names: AB1010;Drug: Gemcitabine<br>* Gemcitabine at 1000 mg/m2 by intravenous infusion<br>* Other names: Gemzar;|
| Placebo Comparator: Placebo & gemcitabine<br>Participants receive matching placebo, given orally twice daily, plus gemcitabine at 1000mg/m2 by intravenous infusion during 30 minutes, once every 7 days, for up to 7 weeks, followed by a week of rest. Subsequent cycles should consist of an IV infusion, once every 7 days, for 3 consecutive weeks out of every 4 weeks, until disease progression, death, limiting toxicity or patient consent withdrawal. | Drug: Placebo<br>* Matching placebo given orally twice daily<br>Drug: Gemcitabine<br>* Gemcitabine at 1000 mg/m2 by intravenous infusion<br>* Other names: Gemzar;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall survival is defined as time in months from the randomization date to the date of death due to any cause. If a patient is not known to have died, then OS will be censored at the date of last known date patient alive. | From day of randomization to the date of death, assessed up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival rate | Defined as the proportion of patients alive at each time point, estimated with Kaplan-Meier distribution. | Every 24 weeks, assessed up to 60 months | 
| Progression Free Survival (PFS) | Progression Free Survival is defined as the time from the randomization date until the date of earliest evidence of disease progression or death, for participants who progressed or died before subsequent cancer therapy. Disease progression will be assessed by the investigator on CT scan according to RECIST 1.1 criteria. | From day of randomization to disease progression or death, whichever came first, assessed up to 60 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pancreatic cancer, Advanced pancreatic cancer, Metastatic pancreatic cancer, Gemcitabine, Chemo-naive