An Investigational Immuno-therapy Study of Temozolomide Plus Radiation Therapy With Nivolumab or Placebo, for Newly Diagnosed Patients With Glioblastoma (GBM, a Malignant Brain Cancer) (CheckMate548)

May 10, 2024 updated by: Bristol-Myers Squibb

A Randomized Phase 3 Single Blind Study of Temozolomide Plus Radiation Therapy Combined With Nivolumab or Placebo in Newly Diagnosed Adult Subjects With MGMT-Methylated (Tumor O6-methylguanine DNA Methyltransferase) Glioblastoma

The purpose of this study is to evaluate patients with glioblastoma that is MGMT-methylated (the MGMT gene is altered by a chemical change). Patients will receive temozolomide plus radiation therapy. They will be compared to patients receiving nivolumab in addition to temozolomide plus radiation therapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

716

Phase

  • Phase 3

Expanded Access

No longer available outside the clinical trial. 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
      • Liverpool, New South Wales, Australia, 2170
        • Local Institution - 0049
      • St. Leonards, New South Wales, Australia, 2065
        • Local Institution - 0052
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Local Institution - 0050
      • Prahran, Victoria, Australia, 3181
        • Local Institution - 0051
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Local Institution - 0122
  • Austria
      • Linz, Austria, 4020
        • Local Institution - 0062
      • Vienna, Austria, 1090
        • Local Institution - 0061
  • Belgium
      • Brussels, Belgium, 1090
        • Local Institution - 0070
      • Bruxelles, Belgium, 1200
        • Local Institution - 0069
      • Leuven, Belgium, 3000
        • Local Institution - 0071
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • Local Institution - 0046
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Local Institution - 0048
    • Quebec
      • Montreal, Quebec, Canada, H3A 2B4
        • Local Institution - 0047
  • Denmark
      • Copenhagen, Denmark, 2100
        • Local Institution - 0084
      • Odense, Denmark, 5000
        • Local Institution - 0085
  • France
      • Lille Cedex, France, 59037
        • Local Institution - 0043
      • Lyon Cedex 03, France, 69394
        • Local Institution - 0041
      • Marseille, France, 13385
        • Local Institution - 0040
      • Nancy, France, 54035
        • Local Institution - 0042
      • Paris, France, 75010
        • Local Institution - 0038
      • Paris cedex 13, France, 75651
        • Local Institution - 0039
      • Rennes Cedex, France, 35042
        • Local Institution - 0044
      • Toulouse, France, 31100
        • Local Institution - 0045
  • Germany
      • Bonn, Germany, 53127
        • Local Institution - 0055
      • Erlangen, Germany, 91054
        • Local Institution - 0123
      • Frankfurt Am Main, Germany, 60528
        • Local Institution - 0053
      • Freiburg, Germany, 79106
        • Local Institution - 0124
      • Hamburg, Germany, 20246
        • Local Institution - 0057
      • Heidelberg, Germany, 69120
        • Local Institution - 0056
      • Koeln, Germany, 50937
        • Local Institution - 0131
      • Muenster, Germany, 48149
        • Local Institution - 0054
      • Munich, Germany, 81675
        • Local Institution - 0130
      • Regensburg, Germany, 93053
        • Local Institution - 0058
      • Tuebingen, Germany, 72076
        • Local Institution - 0059
  • Israel
      • Petach Tikva, Israel, 49100
        • Local Institution - 0094
      • Tel Aviv, Israel, 64239
        • Local Institution - 0093
  • Italy
      • Bologna, Italy, 40139
        • Local Institution - 0088
      • Milano, Italy, 20133
        • Local Institution - 0089
      • Padova, Italy, 35128
        • Local Institution - 0092
      • Rozzano (milano), Italy, 20089
        • Local Institution - 0127
      • Siena, Italy, 53100
        • Local Institution - 0090
      • Torino, Italy, 10126
        • Local Institution - 0091
  • Japan
      • Kyoto, Japan, 6068507
        • Local Institution - 0109
      • Kyoto, Japan, 612-8555
        • Local Institution - 0108
    • Aichi
      • Nagoya-shi, Aichi, Japan, 4668560
        • Local Institution - 0110
    • Chiba
      • Chiba-shi, Chiba, Japan, 2608677
        • Local Institution - 0099
    • Hiroshima
      • Hiroshima-Shi, Hiroshima, Japan, 7348551
        • Local Institution - 0100
    • Hokkaido
      • Sapporo-shi, Hokkaido, Japan, 0608648
        • Local Institution - 0101
    • Hyogo
      • Kobe-shi, Hyogo, Japan, 650-0017
        • Local Institution - 0105
    • Ibaraki
      • Tsukuba-shi, Ibaraki, Japan, 3058576
        • Local Institution - 0116
    • Ishikawa
      • Kanazawa-shi, Ishikawa, Japan, 9200934
        • Local Institution - 0103
    • Kagoshima
      • Kagoshima-shi, Kagoshima, Japan, 8908520
        • Local Institution - 0102
    • Kanagawa
      • Sagamihara-shi, Kanagawa, Japan, 2520375
        • Local Institution - 0118
    • Kumamoto
      • Kumamoto-shi, Kumamoto, Japan, 8608556
        • Local Institution - 0106
    • Okayama
      • Okayama-shi, Okayama, Japan, 7008558
        • Local Institution - 0120
    • Osaka
      • Hirakata-shi, Osaka, Japan, 5731191
        • Local Institution - 0104
      • Suita, Osaka, Japan, 5650871
        • Local Institution - 0112
    • Saitama
      • Hidaka-shi, Saitama, Japan, 3501298
        • Local Institution - 0121
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan, 1138655
        • Local Institution - 0114
      • Chuo-ku, Tokyo, Japan, 1040045
        • Local Institution - 0111
      • Mitaka-shi, Tokyo, Japan, 181-8611
        • Local Institution - 0107
      • Shinjuku-ku, Tokyo, Japan, 1628666
        • Local Institution - 0115
    • Yamagata
      • Yamagata-shi, Yamagata, Japan, 9909585
        • Local Institution - 0117
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • Local Institution - 0075
      • Groningen, Netherlands, 9713 AP
        • Local Institution - 0074
      • Utrecht, Netherlands, 3584 CX
        • Local Institution - 0072
    • Zuid-Holland
      • Rotterdam, Zuid-Holland, Netherlands, 3015 GD
        • Local Institution - 0073
  • Norway
      • Oslo, Norway, 0424
        • Local Institution - 0083
  • Poland
      • Gdansk, Poland, 80-214
        • Local Institution - 0086
      • Warszawa, Poland, 02-781
        • Local Institution - 0132
  • Russian Federation
      • Moscow, Russian Federation, 105229
        • Local Institution - 0095
      • Moscow, Russian Federation, 115478
        • Local Institution - 0097
  • Spain
      • Badalona-barcelona, Spain, 08916
        • Local Institution - 0126
      • Barcelona, Spain, 08035
        • Local Institution - 0078
      • Barcelona, Spain, 08036
        • Local Institution - 0125
      • Madrid, Spain, 28009
        • Local Institution - 0077
      • Madrid, Spain, 28041
        • Local Institution - 0076
      • Santiago Compostela, Spain, 15706
        • Local Institution - 0080
      • Valencia, Spain, 46014
        • Local Institution - 0079
  • Sweden
      • Lund, Sweden, 221 85
        • Local Institution - 0081
      • Solna, Sweden, 171 64
        • Local Institution - 0082
  • Switzerland
      • Geneve, Switzerland, 1211
        • Local Institution - 0065
      • Lausanne, Switzerland, 1011
        • Local Institution - 0064
      • Zuerich, Switzerland, 8091
        • Local Institution - 0063
  • United Kingdom
      • Glasgow, United Kingdom, G12 0YN
        • Local Institution - 0068
      • London, United Kingdom, NW1 2BU
        • Local Institution - 0067
    • Greater Manchester
      • Manchester, Greater Manchester, United Kingdom, M20 4BX
        • Local Institution - 0066
    • Surrey
      • Sutton, Surrey, United Kingdom, SM2 5PT
        • Local Institution - 0119
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294-3410
        • Local Institution - 0023
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Local Institution - 0003
    • California
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center
      • Los Angeles, California, United States, 90095-1769
        • Local Institution - 0010
      • Sacramento, California, United States, 95816
        • Local Institution - 0128
      • San Diego, California, United States, 92123
        • Local Institution - 0029
      • San Francisco, California, United States, 94143-0372
        • Local Institution - 0006
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Local Institution - 0004
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Local Institution - 0031
    • Florida
      • Miami, Florida, United States, 33136
        • Local Institution - 0087
      • Tampa, Florida, United States, 33612
        • Local Institution - 0030
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Local Institution - 0022
    • Kansas
      • Westwood, Kansas, United States, 66205
        • Local Institution - 0060
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Local Institution - 0018
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Local Institution - 0020
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Local Institution - 0011
      • Boston, Massachusetts, United States, 02215
        • Local Institution - 0028
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Local Institution - 0035
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Local Institution - 0002
    • New Jersey
      • Edison, New Jersey, United States, 08820
        • Local Institution - 0017
      • Hackensack, New Jersey, United States, 07601
        • Local Institution - 0012
    • New York
      • New York, New York, United States, 10032
        • Local Institution - 0015
      • New York, New York, United States, 10065
        • Local Institution - 0024
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Local Institution - 0032
      • Durham, North Carolina, United States, 27710
        • Preston Robert Tisch Brain Tumor Center at Duke University
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Local Institution - 0001
      • Columbus, Ohio, United States, 43210
        • Local Institution - 0027
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Local Institution - 0098
      • Philadelphia, Pennsylvania, United States, 19107
        • Local Institution - 0016
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Local Institution - 0021
    • Tennessee
      • Chattanooga, Tennessee, United States, 37403
        • Erlanger Oncology & Hematology - Univ. of TN
      • Nashville, Tennessee, United States, 37232
        • Local Institution - 0008
    • Texas
      • Dallas, Texas, United States, 75390-8575
        • Local Institution - 0025
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Local Institution - 0009
    • Washington
      • Seattle, Washington, United States, 98122
        • Local Institution - 0005

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • Males and Females, age ≥ 18 years old
  • Newly diagnosed brain cancer or tumor called glioblastoma or GBM
  • Karnofsky performance status of ≥ 70 (able to take care of self)
  • Substantial recovery from surgery resection
  • Tumor test result shows MGMT methylated or indeterminate tumor subtype

Exclusion Criteria:

  • Biopsy-only of GBM with less than 20% of tumor removed
  • 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

Other protocol defined inclusion/exclusion criteria could 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: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nivolumab + Temozolomide + Radiotherapy
Nivolumab: specified dose on specified days; IV (intravenous) infusion Temozolomide: 75 mg (milligram)/meter squared daily during Radiotherapy, 4 week treatment break, 150 mg/meter squared Day 1-5 for Cycle 1 and increased to 200 mg/meter squared Day 1-5 for Cycle2-Cycle 6 as tolerated; orally (additional cycles may be permitted with approval of sponsor) Radiotherapy: 2 gray units (joule of radiation energy per kilogram) 5 times per week for 6 weeks
Drug: Temozolomide
Other Names:
  • Temodar
  • Temodal
  • Temcad
  • TMZ
Radiation: Radiotherapy
Other Names:
  • RT
Drug: Nivolumab
Other Names:
  • BMS-936558
  • Opdivo
  • N
  • Nivo
Placebo Comparator: Nivolumab placebo + Temozolomide + Radiotherapy
Nivolumab Placebo: specified dose on specified days; IV infusion Temozolomide: 75 mg/meter squared daily during Radiotherapy, 4 week treatment break, 150 mg/meter squared Day 1-5 for Cycle 1 and increased to 200 mg/meter squared Day 1-5 for Cycle2-Cycle 6 as tolerated; orally (additional cycles may be permitted with approval of sponsor) Radiotherapy: 2 gray units 5x/week x 6 weeks
Drug: Temozolomide
Other Names:
  • Temodar
  • Temodal
  • Temcad
  • TMZ
Radiation: Radiotherapy
Other Names:
  • RT
Other: Nivolumab Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS) Determined by BICR
Time Frame: From randomization to the date of the first documented tumor progression or death by any cause. (up to approximately 4.5 years)
The time from randomization to the date of the first documented tumor progression or death by any cause. PFS will be determined by a Blinded Independent Central Review (BICR) assessed based on Radiologic Assessment in Neuro-Oncology (RANO) criteria. Specifically, RANO response criteria indicates that within the first 12 weeks of completion of radiotherapy, progression can only be assessed if the majority of the new enhancement is outside of the radiation field or if there is pathologic confirmation of progressive disease.
From randomization to the date of the first documented tumor progression or death by any cause. (up to approximately 4.5 years)
Overall Survival (OS)
Time Frame: From randomization to date of death (up to approximately 4.5 years)
The time from the date of randomization to the date of death. who have not died by the end of the study will be censored to last known date alive. OS is assessed in the randomized population with no corticosteroids at baseline population and in the overall randomized population.
From randomization to date of death (up to approximately 4.5 years)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS) Rates at 12 Months
Time Frame: From randomization to 12 months after first dose
Overall Survival (OS) rate is defined as the percentage of participants surviving at 12 months
From randomization to 12 months after first dose
Overall Survival (OS) Rates at 24 Months
Time Frame: From randomization to 24 months after first dose
Overall Survival (OS) rate is defined as the percentage of participants surviving at 24 months
From randomization to 24 months after first dose
Progression Free Survival (PFS) Based on Investigator Assessment
Time Frame: From randomization to the date of the first documented tumor progression or death by any cause. (up to approximately 4.5 years)
The time from randomization to the date of the first documented tumor progression or death by any cause. PFS will be determined by investigator assessment based Radiologic Assessment in Neuro-Oncology (RANO) criteria. Specifically, RANO response criteria indicates that within the first 12 weeks of completion of radiotherapy, progression can only be assessed if the majority of the new enhancement is outside of the radiation field or if there is pathologic confirmation of progressive disease.
From randomization to the date of the first documented tumor progression or death by any cause. (up to approximately 4.5 years)

Collaborators and Investigators

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

Sponsor

Bristol-Myers Squibb

Collaborators

Ono Pharmaceutical Co. Ltd

Investigators

  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

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)

May 9, 2016

Primary Completion (Actual)

December 22, 2020

Study Completion (Actual)

April 9, 2024

Study Registration Dates

First Submitted

January 26, 2016

First Submitted That Met QC Criteria

January 26, 2016

First Posted (Estimated)

January 29, 2016

Study Record Updates

Last Update Posted (Actual)

May 29, 2024

Last Update Submitted That Met QC Criteria

May 10, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA209-548
  • 2015-004722-34 (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.

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