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

• ClinicalTrials.gov Identifier: NCT00789633
• Recruitment Status: Completed
• First Posted: November 13, 2008
• Last Update Posted: December 17, 2018
• Sponsor: AB Science
• Information provided by (Responsible Party): AB Science

Tracking Information

• First Submitted Date: November 12, 2008
• First Posted Date: November 13, 2008
• Last Update Posted Date: December 17, 2018
• Actual Study Start Date: November 25, 2008
• Actual Primary Completion Date: December 23, 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (submitted: November 12, 2008): Overall survival [ Time Frame: until death ]

Current Secondary Outcome Measures (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 (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 Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Masitinib in Combination With Gemcitabine for Treatment of Patients With Advanced/Metastatic 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
• 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Pancreatic Cancer

Intervention

• 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):1194-1200. doi: 10.1093/annonc/mdv133. Epub 2015 Apr 9.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 27, 2018): 353
• Original Estimated Enrollment (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

Main 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Czechia, France, Lebanon, Romania, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT00789633
• Other Study ID Numbers: 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: AB Science
• Collaborators: Not Provided

Investigators

• Principal Investigator: Gaël Deplanque, MD; Hôpital Saint Joseph, Paris, France

• PRS Account: AB Science
• Verification Date: December 2018