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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
Results First Posted : June 29, 2022
Last Update Posted : June 29, 2022
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

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.

Condition or disease Intervention/treatment Phase
Recurrent Glioblastoma Biological: Nivolumab Biological: Bevacizumab Biological: Ipilimumab Phase 3

Detailed Description:
Allocation: Randomized (Cohorts 1, 2 and Part B of 1c/1d), Non-Randomized (Cohorts 1b, and Part A of 1c/1d)

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 529 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : February 7, 2014
Actual Primary Completion Date : June 17, 2019
Estimated Study Completion Date : January 3, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm N:Nivolumab
Cohort 1, 1c, 1d and 2: Nivolumab specified dose on specified days
Biological: Nivolumab
specified dose on specified days
Other Name: BMS-936558

Experimental: Arm N + I:Nivolumab + Ipilimumab

Cohort 1: Nivolumab specified dose on specified days + Ipilimumab specified dose on specified days, then Nivolumab specified dose on specified days

Cohort 1b: Nivolumab specified dose on specified days + Ipilimumab specified dose on specified days, then Nivolumab specified dose on specified days

Biological: Nivolumab
specified dose on specified days
Other Name: BMS-936558

Biological: Ipilimumab
specified dose on specified days
Other Name: Yervoy

Active Comparator: Arm B: Bevacizumab
Cohort 2: Bevacizumab specified dose on specified days
Biological: Bevacizumab
specified dose on specified days
Other Name: Avastin




Primary Outcome Measures :
  1. Percentage of Participants With Drug-Related Adverse Events Leading to Discontinuation by Worst CTC Grade for All Treated Participants in Cohorts 1, 1b, 1c and 1d Who Permanently Discontinued Study Medication Prior to Completing Four Doses [ Time Frame: Includes events reported between first dose and 30 days after last dose of study therapy (up to 3 doses, up to approximately 2 months) ]
    The percentage of participants who experienced a drug-related adverse event leading to drug discontinuation by worst grade (grade 5 being the worst) prior to complete four-dose treatment. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. MedDRA Version: 24.1

  2. Percentage of Participants With Adverse Events (Worst Grade) in Cohorts 1, 1b, 1c and 1d [ Time Frame: From first dose to 30 days post last dose (up to approximately 34 months). ]
    The percentage of participants who experienced an adverse event by worst grade in each treatment arm. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. MedDRA Version: 24.1

  3. Percentage of Participants With Serious Adverse Events (Worst Grade) in Cohorts 1, 1b, 1c and 1d [ Time Frame: From first dose to 30 days post last dose (up to approximately 34 months). ]
    The percentage of participants who experienced a serious adverse event by worst grade in each treatment arm. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. MedDRA Version: 24.1

  4. Percentage of Participants With Specific Laboratory Abnormalities in Liver Tests in Cohorts 1, 1b, 1c and 1d [ Time Frame: From first dose to 30 days post last dose (up to approximately 34 months). ]

    The percentage of participants who experienced a laboratory abnormality of the liver in each treatment arm.

    MedDRA Version: 24.1

    Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN) Denominator corresponds to participants with at least on one treatment measurement of the corresponding laboratory parameter. Includes laboratory results reported after the first dose and within 30 days of last dose of study therapy.


  5. Percentage of Participants With Specific Laboratory Abnormalities in Thyroid Tests in Cohorts 1, 1b, 1c and 1d [ Time Frame: From first dose to 30 days post last dose (up to approximately 34 months). ]

    The percentage of participants who experienced a laboratory abnormality of the thyroid in each treatment arm.

    MedDRA Version: 24.1

    Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN)

    (A) Within a 2-week window after the abnormal TSH test date. (B) Includes participants with TSH abnormality and with no FT3/FT4 test values in the 2-week window or with non-abnormal value(s) from only one of the two tests and no value from the other test.


  6. Overall Survival (OS) for Cohort 2 [ Time Frame: Time between the date of randomization and the date of death due to any cause (up to 17Jun2019, approximately 5 years) ]

    OS was measured in months from the time of randomization to the event date (death) due to any cause. A participant who has not died will be censored at the last known alive date.

    Based on Kaplan-Meier Estimates. Hazard ratio from Cox proportional hazard model stratified by presence of measurable lesions at baseline per IVRS. P-value from log-rank test stratified by presence of measurable lesions at baseline per IVRS.



Secondary Outcome Measures :
  1. Overall Survival (OS) at 12 Months for Cohort 2 [ Time Frame: From randomization to 12 months following randomization ]
    OS(12) is measured as the percentage of participants alive at 12 months per Kaplan-Meier curve of OS. Z test with variance estimation based on Greenwood formula using log(-log) transformation.

  2. Overall Survival (OS) for Cohorts 1c and 1d [ Time Frame: Time between the date of randomization and the date of death due to any cause (up to 17Jun2019, approximately 5 years) ]

    OS was measured in months from the time of randomization (Part B) or time of treatment (Part A) to the event date (death) due to any cause. A participant who has not died will be censored at the last known alive date.

    Based on Kaplan-Meier Estimates.


  3. Progression Free Survival (PFS) for Cohort 2 [ Time Frame: Time from randomization to the date of the first documented tumor progression or death due to any cause (up to 17Jun2019, approximately 5 years) ]
    PFS was measured in months from the time of randomization to the date of the first documented tumor progression or death due to any cause. Based on Kaplan-Meier Estimates. Hazard ratio from Cox proportional hazard model stratified by presence of measurable lesions at baseline per IVRS.

  4. Objective Response Rate (ORR) for Cohort 2 [ Time Frame: Time from randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 31 months) ]

    ORR was measured by the percentage of participants whose best overall response (BOR) is confirmed Complete Response (CR) or Partial Response (PR) divided by response evaluable participants. The best overall response (BOR) is determined once all the data for the participant is known. BOR is defined as the best response designation, as determined by investigators, recorded between the date of randomization and the date of objectively documented progression per RANO criteria, the date of subsequent therapy, or date of surgical resection, whichever occurs first.

    Confidence interval based on the Clopper and Pearson method. For the comparison of the odds ratio of Nivolumab over Bevacizumab, the Cochran-Mantel-Haenszel (CMH) method of weighting was utilized.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02017717


Locations
Show Show 60 study locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  Study Documents (Full-Text)

Documents provided by Bristol-Myers Squibb:
Study Protocol  [PDF] November 16, 2016
Statistical Analysis Plan  [PDF] September 22, 2016

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02017717    
Other Study ID Numbers: CA209-143
2013-003738-34 ( EudraCT Number )
First Posted: December 23, 2013    Key Record Dates
Results First Posted: June 29, 2022
Last Update Posted: June 29, 2022
Last Verified: May 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Bevacizumab
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action