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

Recurrent Glioblastoma Clinical Trial

— CheckMate 143  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02017717
• Other study ID #: CA209-143
• Secondary ID: 2013-003738-34
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 7, 2014
• Est. completion date: April 8, 2024

Study information

• Verified date: October 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 529
• Est. completion date: April 8, 2024
• Est. primary completion date: June 17, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Glioblastoma
• Recurrent Glioblastoma

Intervention

Biological:
• Nivolumab
specified dose on specified days
• Bevacizumab
specified dose on specified days
• Ipilimumab
specified dose on specified days

Locations

Country	Name	City	State
Australia	Local Institution	East Bentleigh	Victoria
Australia	Local Institution - 0034	East Bentleigh	Victoria
Australia	Local Institution	Heidelberg	Victoria
Australia	Local Institution - 0033	Heidelberg	Victoria
Australia	Local Institution	Liverpool	New South Wales
Australia	Local Institution - 0035	Liverpool	New South Wales
Australia	Local Institution	Nedlands	Western Australia
Australia	Local Institution - 0032	Nedlands	Western Australia
Belgium	Local Institution	Brussels
Belgium	Local Institution - 0050	Brussels
Belgium	Local Institution	Bruxelles
Belgium	Local Institution - 0051	Bruxelles
Denmark	Aarhus University Hospital	Aarhus C
Denmark	Local Institution - 0058	Aarhus C
Denmark	Local Institution - 0057	Odense C
Denmark	Odense University Hospital	Odense C
France	Local Institution	Bron cedex
France	Local Institution - 0062	Bron cedex
France	Local Institution	Marseille Cedex 5
France	Local Institution - 0063	Marseille Cedex 5
France	Local Institution	Paris
France	Local Institution - 0068	Paris
France	Local Institution	Paris cedex 13
France	Local Institution - 0064	Paris cedex 13
Germany	Local Institution - 0037	Bonn
Germany	Universitaetsklinikum Bonn	Bonn
Germany	Klinikum Der J. W. Goethe-Universitaet Frankfurt/Main	Frankfurt Am Main
Germany	Local Institution - 0036	Frankfurt Am Main
Germany	Local Institution	Heidelberg
Germany	Local Institution - 0038	Heidelberg
Germany	Local Institution - 0041	Muenster
Germany	Universitaetsklinikum Muenster	Muenster
Italy	Local Institution	Bologna
Italy	Local Institution - 0010	Bologna
Italy	Local Institution	Milano
Italy	Local Institution - 0011	Milano
Italy	Local Institution	Siena
Italy	Local Institution - 0012	Siena
Italy	Azienda Ospedaliera Citta della Salute e della Scienza	Torino
Italy	Local Institution - 0013	Torino
Netherlands	Local Institution	Amsterdam
Netherlands	Local Institution - 0067	Amsterdam
Netherlands	Local Institution	Groningen
Netherlands	Local Institution - 0066	Groningen
Poland	Local Institution	Gdansk
Poland	Local Institution - 0060	Gdansk
Poland	Local Institution	Warszawa
Poland	Local Institution - 0059	Warszawa
Spain	Local Institution	Barcelona
Spain	Local Institution - 0047	Barcelona
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution - 0045	Madrid
Spain	Local Institution - 0046	Madrid
Spain	Local Institution	Pamplona
Spain	Local Institution - 0070	Pamplona
Switzerland	Centre hospitalier universitaire Vaudois (CHUV)	Lausanne
Switzerland	Local Institution - 0039	Lausanne
Switzerland	Local Institution - 0040	Zuerich
Switzerland	UniversitaetsSpital Zurich	Zuerich
United Kingdom	Local Institution	Liverpool
United Kingdom	Local Institution - 0017	Liverpool
United Kingdom	Local Institution	London	Greater London
United Kingdom	Local Institution - 0018	London	Greater London
United Kingdom	Local Institution	Manchester	Greater Manchester
United Kingdom	Local Institution - 0015	Manchester	Greater Manchester
United States	Local Institution - 0002	Atlanta	Georgia
United States	Winship Cancer Institute	Atlanta	Georgia
United States	Anschutz Cancer Pavilion	Aurora	Colorado
United States	Local Institution - 0021	Aurora	Colorado
United States	Johns Hopkins University School Of Medicine	Baltimore	Maryland
United States	Local Institution - 0008	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Med Ctr	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Local Institution - 0006	Boston	Massachusetts
United States	Local Institution - 0043	Boston	Massachusetts
United States	Local Institution - 0056	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Local Institution - 0023	Charleston	South Carolina
United States	Medical University Of South Carolina	Charleston	South Carolina
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University Of Virginia Health System	Charlottesville	Virginia
United States	Cleveland Clinic	Cleveland	Ohio
United States	Local Institution - 0049	Cleveland	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Henry Ford Health System	Detroit	Michigan
United States	Henry Ford Health System	Detroit	Michigan
United States	Local Institution - 0007	Durham	North Carolina
United States	Preston Robert Tisch Brain Tumor Center at Duke University	Durham	North Carolina
United States	Local Institution - 0024	Houston	Texas
United States	University Of Texas Md Anderson Cancer Ctr	Houston	Texas
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Local Institution - 0009	Los Angeles	California
United States	Local Institution - 0055	Los Angeles	California
United States	UCLA Neuro-Oncology Program	Los Angeles	California
United States	Local Institution - 0005	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Local Institution - 0001	New Haven	Connecticut
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	Local Institution - 0003	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Thomas Jefferson University - Clinical Research Institute	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Local Institution - 0014	San Francisco	California
United States	The Regents of the University of California, San Francisco	San Francisco	California
United States	Local Institution - 0020	Seattle	Washington
United States	Swedish Neuroscience Institute	Seattle	Washington
United States	University of Washington - Seattle Cancer Care Alliance	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Moffitt Cancer Center	Tampa	Florida
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Denmark,  France,  Germany,  Italy,  Netherlands,  Poland,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	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	Percentage of Participants With Adverse Events (Worst Grade) in Cohorts 1, 1b, 1c and 1d	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	From first dose to 30 days post last dose (up to approximately 34 months).
Primary	Percentage of Participants With Serious Adverse Events (Worst Grade) in Cohorts 1, 1b, 1c and 1d	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	From first dose to 30 days post last dose (up to approximately 34 months).
Primary	Percentage of Participants With Specific Laboratory Abnormalities in Liver Tests in Cohorts 1, 1b, 1c and 1d	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.	From first dose to 30 days post last dose (up to approximately 34 months).
Primary	Percentage of Participants With Specific Laboratory Abnormalities in Thyroid Tests in Cohorts 1, 1b, 1c and 1d	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.	From first dose to 30 days post last dose (up to approximately 34 months).
Primary	Overall Survival (OS) for Cohort 2	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.	Time between the date of randomization and the date of death due to any cause (up to 17Jun2019, approximately 5 years)
Secondary	Overall Survival (OS) at 12 Months for Cohort 2	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.	From randomization to 12 months following randomization
Secondary	Overall Survival (OS) for Cohorts 1c and 1d	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.	Time between the date of randomization and the date of death due to any cause (up to 17Jun2019, approximately 5 years)
Secondary	Progression Free Survival (PFS) for Cohort 2	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.	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	Objective Response Rate (ORR) for Cohort 2	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.	Time from randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 31 months)

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls