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An Investigational Immuno-therapy Study of Nivolumab Compared to Temozolomide, Each Given With Radiation Therapy, for Newly-diagnosed Patients With Glioblastoma (GBM, a Malignant Brain Cancer) (CheckMate 498)

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ClinicalTrials.gov Identifier: NCT02617589
Recruitment Status : Active, not recruiting
First Posted : December 1, 2015
Results First Posted : February 3, 2021
Last Update Posted : February 3, 2021
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE November 26, 2015
First Posted Date  ICMJE December 1, 2015
Results First Submitted Date  ICMJE November 30, 2020
Results First Posted Date  ICMJE February 3, 2021
Last Update Posted Date February 3, 2021
Actual Study Start Date  ICMJE March 1, 2016
Actual Primary Completion Date January 17, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 15, 2021)
Overall Survival (OS) [ Time Frame: up to 3 years ]
OS is defined as the time between the date of randomization and the date of death due to any cause. A participant who has not died will be censored at the last known alive date.
Original Primary Outcome Measures  ICMJE
 (submitted: November 26, 2015)
Overall Survival (OS) [ Time Frame: Approximately 3 years ]
Overall survival: Defined as the time between the date of randomization and the date of death due to any cause
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 15, 2021)
  • Progression Free Survival (PFS) [ Time Frame: up to 3 years ]
    PFS is defined as the time from randomization to the date of the first documented tumor progression or death due to any cause. Participants who did not have disease progression or who did not die will be censored at the date of last tumor assessment. Participants who did not have any on study tumor assessment and did not have tumor progression or die will be censored at the randomization date. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last tumor assessment prior to initiation of the subsequent anti-cancer therapy. Participants who had surgical resection post start of study treatment will be censored at the last tumor assessment date prior to initiation of surgical resection. PFS was determined by investigator reported response based on RANO criteria
  • OS at 24 Months [ Time Frame: at 24 Months ]
    The OS rate at 24 months of nivolumab + RT and RT + TMZ was estimated as Kaplan-Meier probability of survival at 24 months.
  • OS in Tumor Mutational Burden (TMB) High Population [ Time Frame: up to 3 years ]
    OS is defined as the time between the date of randomization and the date of death due to any cause. A participant who has not died will be censored at the last known alive date.
  • PFS in Tumor Mutational Burden (TMB) High Population [ Time Frame: up to 3 years ]
    PFS is defined as the time from randomization to the date of the first documented tumor progression or death due to any cause. Participants who did not have disease progression or who did not die will be censored at the date of last tumor assessment. Participants who did not have any on study tumor assessment and did not have tumor progression or die will be censored at the randomization date. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last tumor assessment prior to initiation of the subsequent anti-cancer therapy. Participants who had surgical resection post start of study treatment will be censored at the last tumor assessment date prior to initiation of surgical resection. PFS was determined by investigator reported response based on RANO criteria
Original Secondary Outcome Measures  ICMJE
 (submitted: November 26, 2015)
  • Progression free survival (PFS) [ Time Frame: Approximately 24 months ]
    Progression free survival: Defined as the time from randomization to the date of the first documented tumor progression or death due to any cause
  • Overall survival [ Time Frame: Approximately 24 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Investigational Immuno-therapy Study of Nivolumab Compared to Temozolomide, Each Given With Radiation Therapy, for Newly-diagnosed Patients With Glioblastoma (GBM, a Malignant Brain Cancer)
Official Title  ICMJE A Randomized Phase 3 Open Label Study of Nivolumab vs Temozolomide Each in Combination With Radiation Therapy in Newly Diagnosed Adult Subjects With Unmethylated MGMT (Tumor O-6-methylguanine DNA Methyltransferase) Glioblastoma (CheckMate 498: CHECKpoint Pathway and Nivolumab Clinical Trial Evaluation 498)
Brief Summary The purpose of this study is to evaluate patients with glioblastoma that is MGMT-unmethylated (the MGMT gene is not altered by a chemical change). Patients will receive Nivolumab every two weeks in addition to radiation therapy, and then every four weeks. They will be compared to patients receiving standard therapy with temozolomide in addition to radiation therapy.
Detailed Description Not Provided
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 Brain Cancer
Intervention  ICMJE
  • Drug: Nivolumab
  • Drug: Temozolomide
  • Radiation: Radiotherapy
Study Arms  ICMJE
  • Experimental: Nivolumab + Radiotherapy Arm
    Nivolumab IV infusion + Radiotherapy dose as specified
    Interventions:
    • Drug: Nivolumab
    • Radiation: Radiotherapy
  • Active Comparator: Temozolomide + Radiotherapy Arm
    Temozolomide + Radiotherapy dose as specified
    Interventions:
    • Drug: Temozolomide
    • Radiation: Radiotherapy
Publications * Woroniecka K, Fecci PE. Immuno-synergy? Neoantigen vaccines and checkpoint blockade in glioblastoma. Neuro Oncol. 2020 Sep 29;22(9):1233-1234. doi: 10.1093/neuonc/noaa170.

*   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: January 15, 2021)
560
Original Estimated Enrollment  ICMJE
 (submitted: November 26, 2015)
550
Estimated Study Completion Date  ICMJE August 31, 2021
Actual Primary Completion Date January 17, 2019   (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:

  • Males and Females, age ≥ 18 years old
  • Newly-diagnosed brain cancer or tumor called glioblastoma or GBM
  • Tumor test result shows MGMT unmethylated type
  • Karnofsky performance status of ≥ 70 (able to care for self)

Exclusion Criteria:

  • Prior treatment for GBM (other than surgical resection)
  • Any known tumor outside of the brain
  • Recurrent or secondary GBM
  • Active known or suspected autoimmune disease
  • Biopsy with less than 20% of tumor removed
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (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,   Austria,   Belgium,   Canada,   Denmark,   France,   Germany,   Israel,   Italy,   Japan,   Netherlands,   Norway,   Poland,   Russian Federation,   Spain,   Sweden,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02617589
Other Study ID Numbers  ICMJE CA209-498
2015-003739-37 ( 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 Ono Pharmaceutical Co. Ltd
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date January 2021

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