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

Phase 3
Completed
Conditions
Pancreatic Cancer
Interventions
Registration Number
NCT00789633
Lead Sponsor
AB Science
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
353
Inclusion Criteria
  1. Histologically or cytologically confirmed adenocarcinoma of the pancreas
  2. Chemo naïve patients 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. Men and women, age >18 years
  5. 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.
  6. Patient should be able and willing to comply with study visits and procedures as per protocol.
  7. 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
  1. 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
  2. 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
  3. Any anti-tumor therapy (any chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy) within 6 months prior to baseline
  4. Treatment with any investigational agent within 4 weeks prior to baseline

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo & gemcitabinePlaceboParticipants 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.
Masitinib & gemcitabineGemcitabineParticipants 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.
Placebo & gemcitabineGemcitabineParticipants 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.
Masitinib & gemcitabineMasitinibParticipants 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.
Primary Outcome Measures
NameTimeMethod
Overall Survival (OS)From day of randomization to the date of death, assessed up to 60 months

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.

Secondary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS)From day of randomization to disease progression or death, whichever came first, assessed up to 60 months

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.

Survival rateEvery 24 weeks, assessed up to 60 months

Defined as the proportion of patients alive at each time point, estimated with Kaplan-Meier distribution.

Trial Locations

Locations (65)

Hôpital André Mignot

🇫🇷

Le Chesnay, France

Emergency Clinical Hospital

🇷🇴

Constanta, Romania

Oncology Surgery

🇨🇿

Kutná Hora, Czechia

Teaching Hospital Na Bulovce

🇨🇿

Prague 8, Czechia

Department of Oncology Teaching Hospital Olomouc

🇨🇿

Olomouc, Czechia

Hospital Chomutov

🇨🇿

Chomutov, Czechia

Metro MN CCOP

🇺🇸

Saint Louis Park, Minnesota, United States

Berkshire Hematology Oncology

🇺🇸

Pittsfield, Massachusetts, United States

Hôpital Privé d'Antony

🇫🇷

Antony, France

Teaching Hospital Brno-Bohunice

🇨🇿

Brno, Czechia

Medical & Surgical Specialists

🇺🇸

Galesburg, Illinois, United States

The Valley Hospital

🇺🇸

Paramus, New Jersey, United States

Municipal Clinical Hospital

🇷🇴

Arad, Romania

Middle East Institute of Health- Bsaleem

🇱🇧

Metn, Lebanon

CHU de la Cavale Blanche

🇫🇷

Brest, France

CHU Amiens

🇫🇷

Amiens, France

County Hospital

🇷🇴

Satu Mare, Romania

Hôpital Edouard Herriot

🇫🇷

Lyon, France

Hôpital Tenon

🇫🇷

Paris, France

Centre Gastro-Loire

🇫🇷

Gien, France

Hotel Dieu de France

🇱🇧

Beirut, Lebanon

Centre Catherine de Sienne

🇫🇷

Nantes, France

Saint Georges Hospital UMC

🇱🇧

Beirut, Lebanon

Groupe Hospitalier Diaconesse Croix Saint Simon

🇫🇷

Paris, France

Pelica Impex SRL Hospital

🇷🇴

Pelica Impex, Romania

CHU Brabois

🇫🇷

Vandoeuvre lès Nancy, France

Saint Joseph Hospital Baouchrieh

🇱🇧

Metn, Lebanon

Hammoud Hospital University Medical Center

🇱🇧

Saida, Lebanon

Decatur Memorial Hospital

🇺🇸

Decatur, Illinois, United States

CHU de Caen

🇫🇷

Caen, France

CHU Hôtel Dieu

🇫🇷

Nantes, France

Hôpital Victor Jousselin

🇫🇷

Dreux, France

Institut Sainte-Catherine

🇫🇷

Avignon, France

Institut Daniel Hollard

🇫🇷

Grenoble, France

CHD Les Oudairies

🇫🇷

La Roche sur Yon, France

Centre Hospitalier de Longjumeau

🇫🇷

Longjumeau, France

Hôpital de la Source

🇫🇷

Orléans, France

Hôpital Privé Jean Mermoz

🇫🇷

Lyon, France

Centre Léon Bérard

🇫🇷

Lyon, France

Hôpital Hôtel Dieu

🇫🇷

Paris, France

Polyclinique Francheville

🇫🇷

Perigueux, France

Hôpital Haut-Lévêque

🇫🇷

Pessac, France

Hôpital Hautepierre

🇫🇷

Strasbourg, France

Hôpital Paul Brousse

🇫🇷

Villejuif, France

Hôpital Saint-André

🇫🇷

Bordeaux, France

Hôpital Jean Minjoz

🇫🇷

Besançon, France

Hôpital Robert Boulin

🇫🇷

Libourne, France

MD Anderson

🇺🇸

Orlando, Florida, United States

Eastern Connecticut Hematology and Oncology (ECHO)

🇺🇸

Norwich, Connecticut, United States

The Emory Clinic

🇺🇸

Atlanta, Georgia, United States

Saint Luke's Cancer Institute

🇺🇸

Kansas City, Missouri, United States

Southeastern Medical Oncology Center

🇺🇸

Goldsboro, North Carolina, United States

Hospital na Homolce

🇨🇿

Prague, Czechia

CHU Henri Mondor

🇫🇷

Créteil, France

Teaching Hospital Královské

🇨🇿

Prague 10, Czechia

Groupement Hospitalier Universitaire Nord - Beaujon

🇫🇷

Clichy, France

Hôpital Claude Huriez

🇫🇷

Lille, France

Assistance Publique des Hôpitaux de Marseille

🇫🇷

Marseille, France

Hôpital Saint Joseph

🇫🇷

Marseille, France

Centre Hospitalier Belfort - Montbéliard

🇫🇷

Montbeliard, France

Hôpital Saint-Joseph

🇫🇷

Paris, France

Rafik Hariri University Hospital

🇱🇧

Beirut, Lebanon

Makassed General Hospital Tarik Jadide

🇱🇧

Beirut, Lebanon

Henry Ford Health System

🇺🇸

Detroit, Michigan, United States

Oregon Health & Science University

🇺🇸

Portland, Oregon, United States

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