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A Study of the Effectiveness and Safety of Nivolumab Compared to Bevacizumab and of Nivolumab With or Without Ipilimumab in Glioblastoma Patients (CheckMate 143)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02017717
Recruitment Status : Active, not recruiting
First Posted : December 23, 2013
Last Update Posted : April 30, 2019
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE December 17, 2013
First Posted Date  ICMJE December 23, 2013
Last Update Posted Date April 30, 2019
Actual Study Start Date  ICMJE January 27, 2014
Actual Primary Completion Date January 10, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 30, 2015)
  • Cohorts 1,1b, 1c and 1d : Safety and tolerability based on drug related events leading to permanent discontinuation prior to completing 4 doses [ Time Frame: Approximately up to 8 months ]
  • Cohort 2: Overall Survival (OS) [ Time Frame: Approximately 36 months ]
    OS of Nivolumab versus Bevacizumab. Overall Survival is defined as the time between the date of randomization and the date of death due to any cause
Original Primary Outcome Measures  ICMJE
 (submitted: December 20, 2013)
  • Cohort 1: Safety and tolerability based on drug related events leading to permanent discontinuation prior to completing 4 doses [ Time Frame: Approximately up to 8 months ]
  • Cohort 2: Overall Survival (OS) [ Time Frame: After 176 death events (approximately 44 months) ]
    OS of Nivolumab, or Nivolumab in combination with Ipilimumab versus Bevacizumab. Overall Survival is defined as the time between the date of randomization and the date of death due to any cause
Change History Complete list of historical versions of study NCT02017717 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 30, 2015)
  • Cohort 2: Overall Survival rate (OS) [ Time Frame: Approximately 36 months ]
    Comparing OS between Nivolumab and Bevacizumab
  • Cohort 2: Progression Free Survival (PFS) [ Time Frame: Approximately 36 months ]
    Comparing PFS between Nivolumab and Bevacizumab PFS is defined as the time from randomization to the date of the first documented tumor progression or death due to any cause
  • Cohort 2: Objective Response Rate(ORR) [ Time Frame: Approximately 36 months ]
    Comparing ORR between Nivolumab and Bevacizumab ORR is defined as the number of subjects whose best overall response (BOR) is Complete Response (CR) or Partial Response (PR) divided by all randomized subjects
Original Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2013)
  • Progression Free Survival (PFS) [ Time Frame: After 176 death events (approximately 44 months) ]
    Comparing PFS between Nivolumab, or Nivolumab in combination with Ipilimumab versus Bevacizumab. PFS is defined as the time from randomization to the date of the first documented tumor progression or death due to any cause
  • Objective Response Rate(ORR) [ Time Frame: After 176 death events (approximately 44 months) ]
    Comparing ORR between Nivolumab, or Nivolumab in combination with Ipilimumab versus Bevacizumab. ORR is defined as the number of subjects whose best overall response (BOR) is Complete Response (CR) or Partial Response (PR) divided by all randomized subjects
  • Overall Survival (OS) [ Time Frame: After 176 death events (Approximately 44 months) ]
    Comparing OS between Nivolumab in combination with Ipilimumab versus Nivolumab
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of the Effectiveness and Safety of Nivolumab Compared to Bevacizumab and of Nivolumab With or Without Ipilimumab in Glioblastoma Patients
Official Title  ICMJE A Randomized Phase 3 Open Label Study of Nivolumab Versus Bevacizumab and Multiple Phase 1 Safety Cohorts of Nivolumab or Nivolumab in Combination With Ipilimumab Across Different Lines of Glioblastoma
Brief Summary The purpose of the study is to compare the efficacy and safety of nivolumab administered alone versus bevacizumab in patients diagnosed with recurrent glioblastoma (a type of brain cancer, also known as GBM), and to evaluate the safety and tolerability of nivolumab administered alone or in combination with ipilimumab in patients with different lines of GBM therapy.
Detailed Description Allocation: Randomized (Cohort 1 and 2), Non-Randomized (Cohorts 1b, 1c and 1d)
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Recurrent Glioblastoma
Intervention  ICMJE
  • Biological: Nivolumab
    Other Name: BMS-936558
  • Biological: Bevacizumab
    Other Name: Avastin
  • Biological: Ipilimumab
    Other Name: Yervoy
Study Arms  ICMJE
  • Experimental: Arm N:Nivolumab
    Cohort 1, 1c, 1d and 2: Nivolumab 3mg/kg intravenously once every 2 weeks until disease progression or unacceptable toxicity
    Intervention: Biological: Nivolumab
  • Experimental: Arm N + I:Nivolumab + Ipilimumab

    Cohort 1: Nivolumab 1mg/kg + Ipilimumab 3mg/kg intravenously every 3 weeks x 4 doses, then Nivolumab 3mg/kg every 2 weeks until disease progression or unacceptable toxicity

    Cohort 1b: Nivolumab 3mg/kg + Ipilimumab 1mg/kg intravenously every 3 weeks for 4 doses, then Nivolumab 3mg/kg every 2 weeks thereafter until disease progression or unacceptable toxicity

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Active Comparator: Arm B: Bevacizumab
    Cohort 2: Bevacizumab 10 mg/kg intravenously once every 2 weeks until disease progression or unacceptable toxicity
    Intervention: Biological: Bevacizumab
Publications * Not Provided

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 22, 2017)
626
Original Estimated Enrollment  ICMJE
 (submitted: December 20, 2013)
260
Estimated Study Completion Date  ICMJE May 2, 2019
Actual Primary Completion Date January 10, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • Subjects with histologically confirmed Grade IV malignant glioma
  • Previous treatment with radiotherapy and temozolomide (Cohorts 1, 1b and 2 only)
  • First recurrence of GBM (Cohorts 1, 1b and 2 only)
  • First diagnosis of GBM with resectable disease (Cohorts 1c Part A only)
  • First diagnosis of unmethylated MGMT GBM (Cohort 1d and Cohort 1c Part B only)
  • Karnofsky performance score of 70 or higher

Exclusion Criteria:

  • More than 1 recurrence of GBM (Cohorts 1, 1b and 2 only)
  • Any recurrence of GBM (Cohorts 1c and 1d only)
  • Presence of extracranial metastatic or leptomeningeal disease
  • Active, known or suspected autoimmune disease
  • Clinically significant cardiovascular disease
  • Prior bevacizumab or other Vascular Endothelial Growth Factor (VEGF) or anti-angiogenic treatment (Cohort 2 only)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Denmark,   France,   Germany,   Italy,   Netherlands,   Poland,   Spain,   Switzerland,   United Kingdom,   United States
Removed Location Countries Canada
 
Administrative Information
NCT Number  ICMJE NCT02017717
Other Study ID Numbers  ICMJE CA209-143
2013-003738-34 ( EudraCT Number )
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  ICMJE Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP