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

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ClinicalTrials.gov Identifier: NCT02017717

Recruitment Status : Active, not recruiting

First Posted : December 23, 2013

Last Update Posted : November 19, 2021

Sponsor:

Information provided by (Responsible Party):

Bristol-Myers Squibb

Study Description

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 (Cohort 1 and 2), Non-Randomized (Cohorts 1b, 1c and 1d)

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	530 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

Drug Information available for: Bevacizumab Ipilimumab Nivolumab

Genetic and Rare Diseases Information Center resources: Glioblastoma Glioma Neuroepithelioma

U.S. FDA Resources

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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: Approximately up to 8 months ]
Percentage of Participants with Adverse Events (Worst Grade) in Cohorts 1, 1b, 1c and 1d [ Time Frame: Approximately up to 8 months ]
Percentage of Participants with Serious Adverse Events (Worst Grade) in Cohorts 1, 1b, 1c and 1d [ Time Frame: Approximately up to 8 months ]
Percentage of Participants with Specific Laboratory Abnormalities in Liver Tests (Worst Grade) in Cohorts 1, 1b, 1c and 1d [ Time Frame: Approximately up to 8 months ]
Percentage of Participants with Specific Laboratory Abnormalities in Thyroid Tests (Worst Grade) in Cohorts 1, 1b, 1c and 1d [ Time Frame: Approximately up to 8 months ]
Cohort 2: Overall Survival (OS) [ Time Frame: Approximately 36 months ]

Secondary Outcome Measures :

Cohort 2: Overall Survival rate (OS) at 12 months [ Time Frame: 12 months ]
Cohort 2: Progression Free Survival (PFS) [ Time Frame: Approximately 36 months ]
Cohort 2: Objective Response Rate (ORR) [ Time Frame: Approximately 36 months ]
Cohort 1c and 1d: Overall Survival rate (OS) [ Time Frame: Approximately 36 months ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	Child, Adult, Older Adult
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

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)

Contacts and Locations

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 60 study locations

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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294-3410
United States, California
Cedars Sinai Medical Center
Los Angeles, California, United States, 90048
UCLA Neuro-Oncology Program
Los Angeles, California, United States, 90095-1769
The Regents of the University of California, San Francisco
San Francisco, California, United States, 94143-0372
United States, Colorado
Anschutz Cancer Pavilion
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University School Of Medicine
New Haven, Connecticut, United States, 06520
United States, District of Columbia
Georgetown University
Washington, District of Columbia, United States, 20007
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Maryland
Johns Hopkins University School Of Medicine
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Beth Israel Deaconess Med Ctr
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Massachusetts General Hospital
Boston, Massachusetts, United States, 02215
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Levine Cancer Institute
Charlotte, North Carolina, United States, 28204
Preston Robert Tisch Brain Tumor Center at Duke University
Durham, North Carolina, United States, 27710
United States, Ohio
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States, 44106
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
United States, South Carolina
Medical University Of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
University Of Texas Md Anderson Cancer Ctr
Houston, Texas, United States, 77030
United States, Virginia
University of Virginia Health System
Charlottesville, Virginia, United States, 22908
United States, Washington
University of Washington - Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Swedish Neuroscience Institute
Seattle, Washington, United States, 98122
Australia, New South Wales
Local Institution
Liverpool, New South Wales, Australia, 2170
Australia, Victoria
Local Institution
East Bentleigh, Victoria, Australia, 3165
Local Institution
Heidelberg, Victoria, Australia, 3084
Australia, Western Australia
Local Institution
Nedlands, Western Australia, Australia, 6009
Belgium
Local Institution
Brussels, Belgium, 1090
Local Institution
Bruxelles, Belgium, 1200
Denmark
Aarhus University Hospital
Aarhus C, Denmark, 8000
Odense University Hospital
Odense C, Denmark, 5000
France
Local Institution
Bron cedex, France, 69677
Local Institution
Marseille Cedex 5, France, 13385
Local Institution
Paris cedex 13, France, 75651
Local Institution
Paris, France, 75010
Germany
Universitaetsklinikum Bonn
Bonn, Germany, 53127
Klinikum Der J. W. Goethe-Universitaet Frankfurt/Main
Frankfurt Am Main, Germany, 60528
Local Institution
Heidelberg, Germany, 69120
Universitaetsklinikum Muenster
Muenster, Germany, 48149
Italy
Local Institution
Bologna, Italy, 40139
Local Institution
Milano, Italy, 20133
Local Institution
Siena, Italy, 53100
Azienda Ospedaliera Citta della Salute e della Scienza
Torino, Italy, 10126
Netherlands
Local Institution
Amsterdam, Netherlands, 1066CX
Local Institution
Groningen, Netherlands, 9713 AP
Poland
Local Institution
Gdansk, Poland, 80-952
Local Institution
Warszawa, Poland, 02-781
Spain
Local Institution
Barcelona, Spain, 08035
Local Institution
Madrid, Spain, 28009
Local Institution
Madrid, Spain, 28041
Local Institution
Pamplona, Spain, 31008
Switzerland
Centre hospitalier universitaire Vaudois (CHUV)
Lausanne, Switzerland, BT 02252
UniversitaetsSpital Zurich
Zuerich, Switzerland, 8091
United Kingdom
Local Institution
London, Greater London, United Kingdom, NW1 2PG
Local Institution
Manchester, Greater Manchester, United Kingdom, M20 4BX
Local Institution
Liverpool, United Kingdom, L7 8YA

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

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Study Director:	Bristol-Myers Squibb	Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trial Information This link exits the ClinicalTrials.gov site

BMS Clinical Trial Patient Recruiting This link exits the ClinicalTrials.gov site

Investigator Inquiry Form This link exits the ClinicalTrials.gov site

FDA Safety Alerts and Recalls This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Reardon DA, Brandes AA, Omuro A, Mulholland P, Lim M, Wick A, Baehring J, Ahluwalia MS, Roth P, Bähr 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.

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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
Last Update Posted:	November 19, 2021
Last Verified:	November 2021

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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

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