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)

Brain Cancer Clinical Trial

— CheckMate 498  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02617589
• Other study ID #: CA209-498
• Secondary ID: 2015-003739-37
• Status: Completed
• Phase: Phase 3
• Start date: March 1, 2016
• Est. completion date: March 4, 2022

Study information

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

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 560
• Est. completion date: March 4, 2022
• Est. primary completion date: January 17, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 Other protocol-defined inclusion/exclusion criteria apply

Related Conditions & MeSH terms

• Brain Cancer
• Brain Neoplasms
• Glioblastoma

Intervention

Drug:
• Nivolumab

• Temozolomide

Radiation:
• Radiotherapy

Locations

Country	Name	City	State
Australia	Local Institution - 0003	Heidelberg	Victoria
Australia	Local Institution - 0001	Nedlands	Western Australia
Australia	Local Institution - 0002	New South Wales
Australia	Local Institution - 0004	Prahran	Victoria
Australia	Royal North Shore Hospital	St. Leonards	New South Wales
Austria	Local Institution - 0061	Linz
Austria	Local Institution - 0060	Vienna
Belgium	Universitair Ziekenhuis Brussel	Brussels
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	Uz Leuven	Leuven
Canada	Montreal Neurological Institute and Hospital	Montreal	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	BC Cancer - Vancouver	Vancouver	British Columbia
Denmark	Local Institution	Copenhagen
Denmark	Local Institution	Odense
France	Local Institution - 0032	Bron Cedex
France	Local Institution	Lille Cedex
France	Local Institution - 0024	Marseille
France	Local Institution - 0101	Nancy
France	Local Institution - 0023	Paris
France	Local Institution - 0038	Paris cedex 13
France	Centre Eugene Marquis	Rennes
France	Local Institution - 0106	Toulouse
Germany	Local Institution - 0051	Bonn
Germany	Local Institution - 0072	Erlangen
Germany	Local Institution - 0049	Frankfurt am Main
Germany	Local Institution - 0073	Freiburg
Germany	Local Institution - 0054	Hamburg
Germany	Local Institution - 0052	Heidelberg
Germany	Local Institution - 0139	Koeln
Germany	Local Institution - 0050	Muenster
Germany	Local Institution - 0138	Munich
Germany	Local Institution - 0055	Regensburg
Germany	Local Institution - 0056	Tuebingen
Israel	Local Institution - 0096	Petach Tikva
Israel	Local Institution - 0097	Tel Aviv
Italy	Local Institution - 0076	Bologna
Italy	Local Institution - 0079	Milano
Italy	Local Institution - 0126	Padova
Italy	Local Institution - 0135	Rozzano (milano)
Italy	Local Institution - 0078	Siena
Italy	Local Institution - 0077	Torino
Japan	Local Institution - 0128	Bunkyo-ku	Tokyo
Japan	Local Institution - 0125	Chiba-shi	Chiba
Japan	Local Institution - 0114	Chuo-ku	Tokyo
Japan	Local Institution - 0113	Hidaka	Saitama
Japan	Local Institution	Hirakata-shi	Osaka
Japan	Local Institution - 0123	Hiroshima-Shi	Hiroshima
Japan	Local Institution - 0131	Kagoshima-shi	Kagoshima
Japan	Local Institution - 0121	Kanazawa-shi	Ishikawa
Japan	Local Institution - 0129	Kobe	Hyogo
Japan	Local Institution - 0119	Kumamoto-shi	Kumamoto
Japan	Local Institution - 0116	Kyoto-shi	Kyoto
Japan	Local Institution - 0117	Kyoto-shi	Kyoto
Japan	Local Institution - 0118	Mitaka-shi	Tokyo
Japan	Local Institution - 0115	Nagoya-shi	Aichi
Japan	Local Institution - 0134	Okayama-shi	Okayama
Japan	Local Institution - 0133	Sagamihara-shi	Kanagawa
Japan	Local Institution - 0122	Sapporo-shi	Hokkaido
Japan	Local Institution - 0130	Suita-shi	Osaka
Japan	Local Institution - 0112	Tokyo
Japan	Local Institution - 0111	Tsukuba-shi	Ibaraki
Japan	Local Institution - 0110	Yamagata-shi	Yamagata
Netherlands	NKI AVL	Amsterdam
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Erasmus Mc	Rotterdam
Netherlands	Local Institution - 0063	Utrecht
Norway	Local Institution	Oslo
Poland	Local Institution - 0080	Gdansk
Poland	Local Institution - 0081	Warszawa
Russian Federation	Local Institution - 0070	Moscow
Russian Federation	Local Institution - 0105	Moscow
Spain	Local Institution	Badalona-Barcelona
Spain	Local Institution	Barcelona
Spain	Local Institution - 0028	Barcelona
Spain	Local Institution	Madrid
Spain	Local Institution - 0029	Madrid
Spain	Local Institution	Santiago De Compostela
Spain	Local Institution - 0025	Valencia
Sweden	Local Institution	Lund
Sweden	Local Institution	Solna
Switzerland	Local Institution - 0059	Geneve
Switzerland	Local Institution - 0057	Lausanne
Switzerland	Local Institution - 0053	Zuerich
United Kingdom	Beaston West of Scotland Cancer Centre	Glasgow
United Kingdom	University College Hospital	London	Greater London
United Kingdom	Christie Hospital Nhs Found. Trust	Manchester	Greater Manchester
United Kingdom	Royal Marsden Hospital	Sutton	Surrey
United States	Local Institution - 0132	Allentown	Pennsylvania
United States	Emory University - Winship Cancer Institute	Atlanta	Georgia
United States	Johns Hopkins University School Of Medicine	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Medical University Of South Carolina	Charleston	South Carolina
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Local Institution - 0090	Chattanooga	Tennessee
United States	The University Of Chicago	Chicago	Illinois
United States	Local Institution - 0010	Cleveland	Ohio
United States	Local Institution - 0095	Columbus	Ohio
United States	University Of Texas Southwestern Medical Center	Dallas	Texas
United States	Local Institution - 0006	Detroit	Michigan
United States	Preston Robert Tisch Brain Tumor Center at Duke University	Durham	North Carolina
United States	JFK Medical Center	Edison	New Jersey
United States	Local Institution - 0064	Hackensack	New Jersey
United States	University Of Texas Md Anderson Cancer Ctr	Houston	Texas
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Local Institution - 0019	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	University Of Miami Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Columbia University Medical Center (Cumc)	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Local Institution - 0007	Philadelphia	Pennsylvania
United States	Local Institution - 0083	Phoenix	Arizona
United States	Sutter Institute For Medical Research	Sacramento	California
United States	Washington University School OF Medicine-Siteman Cancer Center	Saint Louis	Missouri
United States	Local Institution - 0068	Salt Lake City	Utah
United States	Sharp Memorial Hospital	San Diego	California
United States	The Regents of the University of California, San Francisco	San Francisco	California
United States	Swedish Neuroscience Institute	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	University Of Kansas Medical Center	Westwood	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Ono Pharmaceutical Co. Ltd

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Denmark,  France,  Germany,  Israel,  Italy,  Japan,  Netherlands,  Norway,  Poland,  Russian Federation,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	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.	up to 3 years
Secondary	Kaplan-Meier Plot of Progression Free Survival	PFS was 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 were 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 were censored at the randomization date. Participants who started any subsequent anti-cancer therapy without a prior reported progression were 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 were censored at the last tumor assessment date prior to initiation of surgical resection. PFS was determined by investigator reported response based on the Radiologic Assessment in Neuro-Oncology criteria.	From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 6 years)
Secondary	Overall Survival Rate at 24 Months	The overall survival (OS) rate of (nivolumab + radiation therapy) and (temozolomide + radiation therapy) estimated as Kaplan-Meier probability of survival at 24 months. OS was defined as the time between the date of randomization and the date of death due to any cause. A participant who has not died was censored at the last known alive date.	At 24 Months
Secondary	Overall Survival in Tumor Mutational Burden (TMB) High Population	OS in all randomized participants that are tumor mutational burden high. OS was defined as the time between the date of randomization and the date of death due to any cause. A participant who has not died was censored at the last known alive date.	From randomization to the date of death due to any cause (up to approximately 6 years)
Secondary	Progression Free Survival in Tumor Mutational Burden (TMB) High Population	PFS in all randomized participants that are tumor mutational burden high. PFS was 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 were 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 were censored at the randomization date. Participants who started any subsequent anti-cancer therapy without a prior reported progression were 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 were censored at the last tumor assessment date prior to initiation of surgical resection. PFS was determined by investigator reported response based on the Radiologic Assessment in Neuro-Oncology criteria.	From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 6 years)

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting