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) (CheckMate 498)

March 1, 2023 updated by: Bristol-Myers Squibb

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)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
560

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Expanded Access

Expanded Access

A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved by the U.S. Food and Drug Administration (FDA). Also called compassionate use. There are different expanded access types.
Approved

Approved

  • Available: Expanded access is currently available for this investigational treatment, and patients who are not participants in the clinical study may be able to gain access to the drug, biologic, or medical device being studied.
  • No longer available: Expanded access was available for this intervention previously but is not currently available and will not be available in the future.
  • Temporarily not available: Expanded access is not currently available for this intervention but is expected to be available in the future.
  • Approved for marketing: The intervention has been approved by the U.S. Food and Drug Administration for use by the public.
 for sale to the public. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • New South Wales, Australia, 2170
        • Local Institution - 0002
    • New South Wales
      • St. Leonards, New South Wales, Australia, 2065
        • Royal North Shore Hospital
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Local Institution - 0003
      • Prahran, Victoria, Australia, 3181
        • Local Institution - 0004
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Local Institution - 0001
  • Austria
      • Linz, Austria, 4020
        • Local Institution - 0061
      • Vienna, Austria, 1090
        • Local Institution - 0060
  • Belgium
      • Brussels, Belgium, 1090
        • Universitair Ziekenhuis Brussel
      • Bruxelles, Belgium, 1200
        • Cliniques universitaires Saint-Luc
      • Leuven, Belgium, 3000
        • UZ Leuven
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • BC Cancer - Vancouver
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre
    • Quebec
      • Montreal, Quebec, Canada, H3A 2B4
        • Montreal Neurological Institute and Hospital
  • Denmark
      • Copenhagen, Denmark, 2100
        • Local Institution
      • Odense, Denmark, 5000
        • Local Institution
  • France
      • Bron Cedex, France, 69677
        • Local Institution - 0032
      • Lille Cedex, France, 59037
        • Local Institution
      • Marseille, France, 13005
        • Local Institution - 0024
      • Nancy, France, 54035
        • Local Institution - 0101
      • Paris, France, 75010
        • Local Institution - 0023
      • Paris cedex 13, France, 75651
        • Local Institution - 0038
      • Rennes, France, 35000
        • Centre Eugene Marquis
      • Toulouse, France, 31100
        • Local Institution - 0106
  • Germany
      • Bonn, Germany, 53105
        • Local Institution - 0051
      • Erlangen, Germany, 91054
        • Local Institution - 0072
      • Frankfurt am Main, Germany, 60528
        • Local Institution - 0049
      • Freiburg, Germany, 79106
        • Local Institution - 0073
      • Hamburg, Germany, 20246
        • Local Institution - 0054
      • Heidelberg, Germany, 69120
        • Local Institution - 0052
      • Koeln, Germany, 50937
        • Local Institution - 0139
      • Muenster, Germany, 48149
        • Local Institution - 0050
      • Munich, Germany, 81675
        • Local Institution - 0138
      • Regensburg, Germany, 93053
        • Local Institution - 0055
      • Tuebingen, Germany, 72076
        • Local Institution - 0056
  • Israel
      • Petach Tikva, Israel, 49100
        • Local Institution - 0096
      • Tel Aviv, Israel, 64239
        • Local Institution - 0097
  • Italy
      • Bologna, Italy, 40139
        • Local Institution - 0076
      • Milano, Italy, 20133
        • Local Institution - 0079
      • Padova, Italy, 35128
        • Local Institution - 0126
      • Rozzano (milano), Italy, 20089
        • Local Institution - 0135
      • Siena, Italy, 53100
        • Local Institution - 0078
      • Torino, Italy, 10126
        • Local Institution - 0077
  • Japan
      • Tokyo, Japan, 1628666
        • Local Institution - 0112
    • Aichi
      • Nagoya-shi, Aichi, Japan, 4668560
        • Local Institution - 0115
    • Chiba
      • Chiba-shi, Chiba, Japan, 2608677
        • Local Institution - 0125
    • Hiroshima
      • Hiroshima-Shi, Hiroshima, Japan, 7348551
        • Local Institution - 0123
    • Hokkaido
      • Sapporo-shi, Hokkaido, Japan, 0608648
        • Local Institution - 0122
    • Hyogo
      • Kobe, Hyogo, Japan, 6500017
        • Local Institution - 0129
    • Ibaraki
      • Tsukuba-shi, Ibaraki, Japan, 3058576
        • Local Institution - 0111
    • Ishikawa
      • Kanazawa-shi, Ishikawa, Japan, 9200934
        • Local Institution - 0121
    • Kagoshima
      • Kagoshima-shi, Kagoshima, Japan, 8908520
        • Local Institution - 0131
    • Kanagawa
      • Sagamihara-shi, Kanagawa, Japan, 2520375
        • Local Institution - 0133
    • Kumamoto
      • Kumamoto-shi, Kumamoto, Japan, 8608556
        • Local Institution - 0119
    • Kyoto
      • Kyoto-shi, Kyoto, Japan, 606-8507
        • Local Institution - 0117
      • Kyoto-shi, Kyoto, Japan, 6128555
        • Local Institution - 0116
    • Okayama
      • Okayama-shi, Okayama, Japan, 7008558
        • Local Institution - 0134
    • Osaka
      • Hirakata-shi, Osaka, Japan, 5731191
        • Local Institution
      • Suita-shi, Osaka, Japan, 565-0871
        • Local Institution - 0130
    • Saitama
      • Hidaka, Saitama, Japan, 350-1298
        • Local Institution - 0113
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan, 1138655
        • Local Institution - 0128
      • Chuo-ku, Tokyo, Japan, 1040045
        • Local Institution - 0114
      • Mitaka-shi, Tokyo, Japan, 181-8611
        • Local Institution - 0118
    • Yamagata
      • Yamagata-shi, Yamagata, Japan, 9909585
        • Local Institution - 0110
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • NKI AVL
      • Groningen, Netherlands, 9713 AP
        • Universitair Medisch Centrum Groningen
      • Rotterdam, Netherlands, 3015 CE
        • Erasmus MC
      • Utrecht, Netherlands, 3584CX
        • Local Institution - 0063
  • Norway
      • Oslo, Norway, 0379
        • Local Institution
  • Poland
      • Gdansk, Poland, 80952
        • Local Institution - 0080
      • Warszawa, Poland, 02-781
        • Local Institution - 0081
  • Russian Federation
      • Moscow, Russian Federation, 105229
        • Local Institution - 0070
      • Moscow, Russian Federation, 115478
        • Local Institution - 0105
  • Spain
      • Badalona-Barcelona, Spain, 08916
        • Local Institution
      • Barcelona, Spain, 08035
        • Local Institution
      • Barcelona, Spain, 08036
        • Local Institution - 0028
      • Madrid, Spain, 28041
        • Local Institution
      • Madrid, Spain, 28007
        • Local Institution - 0029
      • Santiago De Compostela, Spain, 15706
        • Local Institution
      • Valencia, Spain, 46014
        • Local Institution - 0025
  • Sweden
      • Lund, Sweden, 221 85
        • Local Institution
      • Solna, Sweden, 171 64
        • Local Institution
  • Switzerland
      • Geneve, Switzerland, 1211
        • Local Institution - 0059
      • Lausanne, Switzerland, 1011
        • Local Institution - 0057
      • Zuerich, Switzerland, 8091
        • Local Institution - 0053
  • United Kingdom
      • Glasgow, United Kingdom, G12 0YN
        • Beaston West of Scotland Cancer Centre
    • Greater London
      • London, Greater London, United Kingdom, NW1 2PG
        • University College Hospital
    • Greater Manchester
      • Manchester, Greater Manchester, United Kingdom, M20 4BX
        • Christie Hospital Nhs Found. Trust
    • Surrey
      • Sutton, Surrey, United Kingdom, SM2 5PT
        • Royal Marsden Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294-3410
        • University of Alabama at Birmingham
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Local Institution - 0083
    • California
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center
      • Los Angeles, California, United States, 90095-1769
        • Local Institution - 0019
      • Sacramento, California, United States, 95816
        • Sutter Institute for Medical Research
      • San Diego, California, United States, 92123
        • Sharp Memorial Hospital
      • San Francisco, California, United States, 94143-0372
        • The Regents of the University of California, San Francisco
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale Cancer Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University Medical Center
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami Sylvester Comprehensive Cancer Center
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University - Winship Cancer Institute
    • Illinois
      • Chicago, Illinois, United States, 60637
        • The University of Chicago
    • Kansas
      • Westwood, Kansas, United States, 66205
        • University of Kansas Medical Center
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Norton Cancer Institute
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University School Of Medicine
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02215
        • Massachusetts General Hospital
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Local Institution - 0006
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School OF Medicine-Siteman Cancer Center
    • New Jersey
      • Edison, New Jersey, United States, 08820
        • JFK Medical Center
      • Hackensack, New Jersey, United States, 07601
        • Local Institution - 0064
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10032
        • Columbia University Medical Center (CUMC)
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Levine Cancer Institute
      • Durham, North Carolina, United States, 27710
        • Preston Robert Tisch Brain Tumor Center at Duke University
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Local Institution - 0010
      • Columbus, Ohio, United States, 43210
        • Local Institution - 0095
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Local Institution - 0132
      • Philadelphia, Pennsylvania, United States, 19107
        • Local Institution - 0007
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Local Institution - 0090
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Texas
      • Dallas, Texas, United States, 75390-8852
        • University of Texas Southwestern Medical Center
      • Houston, Texas, United States, 77030
        • University Of Texas Md Anderson Cancer Ctr
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Local Institution - 0068
    • Washington
      • Seattle, Washington, United States, 98122
        • Swedish Neuroscience Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Nivolumab + Radiotherapy Arm
Nivolumab IV infusion + Radiotherapy dose as specified
Radiation: Radiotherapy
Drug: Nivolumab
Active Comparator: Temozolomide + Radiotherapy Arm
Temozolomide + Radiotherapy dose as specified
Drug: Temozolomide
Radiation: Radiotherapy

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: up to 3 years
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Kaplan-Meier Plot of Progression Free Survival
Time Frame: From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 6 years)
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)
Overall Survival Rate at 24 Months
Time Frame: 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
Overall Survival in Tumor Mutational Burden (TMB) High Population
Time Frame: From randomization to the date of death due to any cause (up to approximately 6 years)
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)
Progression Free Survival in Tumor Mutational Burden (TMB) High Population
Time Frame: From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 6 years)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bristol-Myers Squibb

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Ono Pharmaceutical Co. Ltd

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 17, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 4, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 26, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 26, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 1, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 28, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 1, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CA209-498
  • 2015-003739-37 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings