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

Tracking Information
First Submitted Date ICMJE	November 12, 2008
First Posted Date ICMJE	November 13, 2008
Last Update Posted Date	December 17, 2018
Actual Study Start Date ICMJE	November 25, 2008
Actual Primary Completion Date	December 23, 2011 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 27, 2018)	Overall Survival (OS) [ Time Frame: 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.
Original Primary Outcome Measures ICMJE; (submitted: November 12, 2008)	Overall survival [ Time Frame: until death ]
Change History	Complete list of historical versions of study NCT00789633 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 27, 2018)	Survival rate [ Time Frame: Every 24 weeks, assessed up to 60 months ]Defined as the proportion of patients alive at each time point, estimated with Kaplan-Meier distribution.; Progression Free Survival (PFS) [ Time Frame: 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.
Original Secondary Outcome Measures ICMJE; (submitted: November 12, 2008)	Survival rate, Objective Response Rate, Control Disease Rate, Best Response, Serum level of CA19-9. Progression Free Survival, Time to Progression, Time to Response, Quality of Life questionnaires, Pain and analgesics consumption. [ Time Frame: until death ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Masitinib in Combination With Gemcitabine for Treatment of Patients With Advanced/Metastatic Pancreatic Cancer
Official Title ICMJE	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
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.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Pancreatic Cancer
Intervention ICMJE	Drug: Masitinib Masitinib at 9 mg/kg/day given orally twice daily Other Name: AB1010; Drug: Placebo Matching placebo given orally twice daily; Drug: Gemcitabine Gemcitabine at 1000 mg/m2 by intravenous infusion Other Name: Gemzar
Study Arms	Experimental: Masitinib & gemcitabine 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. Interventions: Drug: Masitinib Drug: Gemcitabine; Placebo Comparator: Placebo & gemcitabine 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. Interventions: Drug: Placebo Drug: Gemcitabine
Publications *	Deplanque G, Demarchi M, Hebbar M, Flynn P, Melichar B, Atkins J, Nowara E, Moyé L, Piquemal D, Ritter D, Dubreuil P, Mansfield CD, Acin Y, Moussy A, Hermine O, Hammel P. A randomized, placebo-controlled phase III trial of masitinib plus gemcitabine in the treatment of advanced pancreatic cancer. Ann Oncol. 2015 Jun;26(6):1194-200. doi: 10.1093/annonc/mdv133. Epub 2015 Apr 9.; Chugh R, Griffith KA, Davis EJ, Thomas DG, Zavala JD, Metko G, Brockstein B, Undevia SD, Stadler WM, Schuetze SM. Doxorubicin plus the IGF-1R antibody cixutumumab in soft tissue sarcoma: a phase I study using the TITE-CRM model. Ann Oncol. 2015 Jul;26(7):1459-64. doi: 10.1093/annonc/mdv171. Epub 2015 Apr 9.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: November 27, 2018)	353
Original Estimated Enrollment ICMJE; (submitted: November 12, 2008)	320
Actual Study Completion Date	August 31, 2012
Actual Primary Completion Date	December 23, 2011 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Czechia, France, Lebanon, Romania, United States
Removed Location Countries	Czech Republic
Administrative Information
NCT Number ICMJE	NCT00789633
Other Study ID Numbers ICMJE	AB07012
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement	Not Provided
Responsible Party	AB Science
Study Sponsor ICMJE	AB Science
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Gaël Deplanque, MD Hôpital Saint Joseph, Paris, France
PRS Account	AB Science
Verification Date	December 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP