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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02017717




Registration number
NCT02017717
Ethics application status
Date submitted
17/12/2013
Date registered
23/12/2013
Date last updated
16/07/2024

Titles & IDs
Public title
A Study of the Effectiveness and Safety of Nivolumab Compared to Bevacizumab and of Nivolumab With or Without Ipilimumab in Glioblastoma Patients
Scientific 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
Secondary ID [1] 0 0
2013-003738-34
Secondary ID [2] 0 0
CA209-143
Universal Trial Number (UTN)
Trial acronym
CheckMate 143
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recurrent Glioblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Nivolumab
Treatment: Other - Bevacizumab
Treatment: Other - Ipilimumab

Experimental: Arm N:Nivolumab - Cohort 1, 1c, 1d and 2: Nivolumab specified dose on specified days

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

Active comparator: Arm B: Bevacizumab - Cohort 2: Bevacizumab specified dose on specified days


Treatment: Other: Nivolumab
specified dose on specified days

Treatment: Other: Bevacizumab
specified dose on specified days

Treatment: Other: Ipilimumab
specified dose on specified days
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Includes events reported between first dose and 30 days after last dose of study therapy (up to 3 doses, up to approximately 2 months)
Primary outcome [2] 0 0
Percentage of Participants With Adverse Events (Worst Grade) in Cohorts 1, 1b, 1c and 1d
Timepoint [2] 0 0
From first dose to 30 days post last dose (up to approximately 34 months).
Primary outcome [3] 0 0
Percentage of Participants With Serious Adverse Events (Worst Grade) in Cohorts 1, 1b, 1c and 1d
Timepoint [3] 0 0
From first dose to 30 days post last dose (up to approximately 34 months).
Primary outcome [4] 0 0
Percentage of Participants With Specific Laboratory Abnormalities in Liver Tests in Cohorts 1, 1b, 1c and 1d
Timepoint [4] 0 0
From first dose to 30 days post last dose (up to approximately 34 months).
Primary outcome [5] 0 0
Percentage of Participants With Specific Laboratory Abnormalities in Thyroid Tests in Cohorts 1, 1b, 1c and 1d
Timepoint [5] 0 0
From first dose to 30 days post last dose (up to approximately 34 months).
Primary outcome [6] 0 0
Overall Survival (OS) for Cohort 2
Timepoint [6] 0 0
Time between the date of randomization and the date of death due to any cause (up to 17Jun2019, approximately 5 years)
Secondary outcome [1] 0 0
Overall Survival (OS) at 12 Months for Cohort 2
Timepoint [1] 0 0
From randomization to 12 months following randomization
Secondary outcome [2] 0 0
Overall Survival (OS) for Cohorts 1c and 1d
Timepoint [2] 0 0
Time between the date of randomization and the date of death due to any cause (up to 17Jun2019, approximately 5 years)
Secondary outcome [3] 0 0
Progression Free Survival (PFS) for Cohort 2
Timepoint [3] 0 0
Time from randomization to the date of the first documented tumor progression or death due to any cause (up to 17Jun2019, approximately 5 years)
Secondary outcome [4] 0 0
Objective Response Rate (ORR) for Cohort 2
Timepoint [4] 0 0
Time from randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 31 months)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/02/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/06/2024
Sample size
Target
Accrual to date
Final
529
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Local Institution - 0035 - Liverpool
Recruitment hospital [2] 0 0
Local Institution - Liverpool
Recruitment hospital [3] 0 0
Local Institution - 0034 - East Bentleigh
Recruitment hospital [4] 0 0
Local Institution - East Bentleigh
Recruitment hospital [5] 0 0
Local Institution - 0033 - Heidelberg
Recruitment hospital [6] 0 0
Local Institution - Heidelberg
Recruitment hospital [7] 0 0
Local Institution - 0032 - Nedlands
Recruitment hospital [8] 0 0
Local Institution - Nedlands
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
3165 - East Bentleigh
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
South Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Tennessee
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Virginia
Country [20] 0 0
United States of America
State/province [20] 0 0
Washington
Country [21] 0 0
Belgium
State/province [21] 0 0
Brussels
Country [22] 0 0
Belgium
State/province [22] 0 0
Bruxelles
Country [23] 0 0
Denmark
State/province [23] 0 0
Aarhus C
Country [24] 0 0
Denmark
State/province [24] 0 0
Odense C
Country [25] 0 0
France
State/province [25] 0 0
Bron cedex
Country [26] 0 0
France
State/province [26] 0 0
Marseille Cedex 5
Country [27] 0 0
France
State/province [27] 0 0
Paris cedex 13
Country [28] 0 0
France
State/province [28] 0 0
Paris
Country [29] 0 0
Germany
State/province [29] 0 0
Bonn
Country [30] 0 0
Germany
State/province [30] 0 0
Frankfurt Am Main
Country [31] 0 0
Germany
State/province [31] 0 0
Heidelberg
Country [32] 0 0
Germany
State/province [32] 0 0
Muenster
Country [33] 0 0
Italy
State/province [33] 0 0
Bologna
Country [34] 0 0
Italy
State/province [34] 0 0
Milano
Country [35] 0 0
Italy
State/province [35] 0 0
Siena
Country [36] 0 0
Italy
State/province [36] 0 0
Torino
Country [37] 0 0
Netherlands
State/province [37] 0 0
Amsterdam
Country [38] 0 0
Netherlands
State/province [38] 0 0
Groningen
Country [39] 0 0
Poland
State/province [39] 0 0
Gdansk
Country [40] 0 0
Poland
State/province [40] 0 0
Warszawa
Country [41] 0 0
Spain
State/province [41] 0 0
Barcelona
Country [42] 0 0
Spain
State/province [42] 0 0
Madrid
Country [43] 0 0
Spain
State/province [43] 0 0
Pamplona
Country [44] 0 0
Switzerland
State/province [44] 0 0
Lausanne
Country [45] 0 0
Switzerland
State/province [45] 0 0
Zuerich
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Greater London
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Greater Manchester
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Liverpool

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02017717
Trial related presentations / 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. No abstract available.
Reardon DA, Brandes AA, Omuro A, Mulholland P, Lim M, Wick A, Baehring J, Ahluwalia MS, Roth P, Bahr O, Phuphanich S, Sepulveda JM, De Souza P, Sahebjam S, Carleton M, Tatsuoka K, Taitt C, Zwirtes R, Sampson J, Weller M. Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma: The CheckMate 143 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Jul 1;6(7):1003-1010. doi: 10.1001/jamaoncol.2020.1024.
Stupp R. Drug development for glioma: are we repeating the same mistakes? Lancet Oncol. 2019 Jan;20(1):10-12. doi: 10.1016/S1470-2045(18)30827-1. Epub 2018 Dec 3. No abstract available.
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02017717