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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02667587
Recruitment Status : Recruiting
First Posted : January 29, 2016
Last Update Posted : May 8, 2018
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Bristol-Myers Squibb

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Brain Neoplasms Drug: Nivolumab Drug: Temozolomide Radiation: Radiotherapy Other: Nivolumab Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 693 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 5, 2016
Estimated Primary Completion Date : February 11, 2022
Estimated Study Completion Date : August 1, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Brain Tumors

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: Nivolumab
Other Names:
  • Opdivo
  • Nivo
  • N
  • BMS-936558

Drug: Temozolomide
Other Names:
  • Temodar
  • TMZ
  • Temodal
  • Temcad

Radiation: Radiotherapy
Other Name: RT

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
  • TMZ
  • Temodal
  • Temcad

Radiation: Radiotherapy
Other Name: RT

Other: Nivolumab Placebo

Primary Outcome Measures :
  1. Overall survival (OS) defined as time from the date of randomization to the date of death. [ Time Frame: Approximately 69 months after first patient first visit ]

Secondary Outcome Measures :
  1. Progression free survival (PFS), defined as the time from randomization to the date of the first documented tumor progression or death to any cause. [ Time Frame: Approximately 69 months after first patient first visit ]
  2. Correlation of PFS and OS [ Time Frame: Approximately 69 months after first patient first visit ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit

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

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 identifier (NCT number): NCT02667587

Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email:
Contact: First line of the email MUST contain NCT# and Site #.

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United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294-3410
Contact: Louis Nabors, Site 0023    205-934-1842      
United States, Arizona
St. Joseph Hospital And Medical Center Recruiting
Phoenix, Arizona, United States, 85013
Contact: Surasak Phuphanich, Site 0003    602-406-7709      
United States, California
Cedars Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Jeremy Rudnick, Site 0026    310-423-4513      
UCLA Neuro-Oncology Program Recruiting
Los Angeles, California, United States, 90095-1769
Contact: Timothy Cloughesy, Site 0010    310-794-3521      
Sutter Institute For Medical Research Recruiting
Sacramento, California, United States, 95816
Contact: Stacy Dandre, Site 0128    916-453-5800      
Sharp Memorial Hospital Recruiting
San Diego, California, United States, 92123
Contact: Charles Redfern, Site 0029    619-502-3241      
The Regents of the University of California, San Francisco Recruiting
San Francisco, California, United States, 94143-0372
Contact: Jennie Taylor, Site 0006         
United States, Connecticut
Yale University School Of Medicine Recruiting
New Haven, Connecticut, United States, 06520
Contact: Joachim Baehring, Site 0004    203-785-7486      
United States, District of Columbia
Georgetown University Recruiting
Washington, District of Columbia, United States, 20007
Contact: Deepa Subramaniam, Site 0031    202-687-8962      
United States, Florida
University Of Miami Sylvester Comprehensive Cancer Center Recruiting
Miami, Florida, United States, 33136
Contact: Macarena De La Fuente, Site 0087    305-243-3111      
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Solmaz Sahebjam, Site 0030    813-745-7991      
United States, Illinois
Local Institution Not yet recruiting
Chicago, Illinois, United States, 60637
Contact: Site 0022         
United States, Kansas
University Of Kansas Medical Center Recruiting
Westwood, Kansas, United States, 66205
Contact: Michael Salacz, Site 0060    913-588-1886      
United States, Kentucky
Norton Cancer Institute Recruiting
Louisville, Kentucky, United States, 40202
Contact: Renato La Rocca, Site 0018         
United States, Maryland
Johns Hopkins University School Of Medicine Recruiting
Baltimore, Maryland, United States, 21287
Contact: Michael Lim, Site 0020         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: David Reardon, Site 0028    617-632-4876      
Local Institution Withdrawn
Boston, Massachusetts, United States, 02215
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02215
Contact: David Reardon, Site 0011    617-643-1933      
United States, Michigan
Henry Ford Health System Recruiting
Detroit, Michigan, United States, 48202
Contact: Tobias Walbert, Site 0035         
United States, Missouri
Washington University School Of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: George Ansstas, Site 0002    314-286-0896      
United States, New Jersey
JFK Medical Center Recruiting
Edison, New Jersey, United States, 08820-3947
Contact: Joseph Landolfi, Site 0017    732-321-7000      
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Samuel Goldlust, Site 0012    551-996-5098      
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Fabio Iwamoto, Site 0015    212-304-5530      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Mariza Daras, Site 0024         
United States, North Carolina
Levine Cancer Institute Recruiting
Charlotte, North Carolina, United States, 28204
Contact: Ashley Sumrall, Site 0032    980-442-5300      
Preston Robert Tisch Brain Tumor Center at Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: Katherine Peters, Site 0033    919-681-9932      
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Manmeet Ahluwalia, Site 0001    216-445-3407      
The Ohio State University Wexner Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Raju Raval, Site 0027    614-685-2435      
United States, Pennsylvania
Lehigh Valley Health Network Recruiting
Allentown, Pennsylvania, United States, 18103
Contact: Suresh Nair, Site 0098    610-402-0636      
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Lyndon Kim, Site 0016    215-503-9110      
United States, South Carolina
Medical University Of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Scott Lindhorst, Site 0021    843-792-9016      
United States, Tennessee
Erlanger Oncology & Hematology - Univ. of TN Recruiting
Chattanooga, Tennessee, United States, 37403
Contact: Robert Graham, Site 0013    423-778-2982      
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Stephen Clark, Site 0008    615-936-8606      
United States, Texas
University Of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Edward Pan, Site 0025    214-648-1929      
Local Institution Withdrawn
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Adam Cohen, Site 0009    801-587-4433      
United States, Washington
Swedish Neuroscience Institute Recruiting
Seattle, Washington, United States, 98122
Contact: Tara Benkers, Site 0005    206-386-3878      
Australia, New South Wales
Local Institution Recruiting
Liverpool, New South Wales, Australia, 2017
Contact: Site 0049         
Royal North Shore Hospital Recruiting
St. Leonards, New South Wales, Australia, 2065
Contact: Mustafa Khasraw, Site 0052    +61294631373      
Australia, Victoria
Local Institution Recruiting
Heidelberg, Victoria, Australia, 3084
Contact: Site 0050         
Local Institution Recruiting
Prahran, Victoria, Australia, 3181
Contact: Site 0051         
Australia, Western Australia
Sir Charles Gairdner Hospital Recruiting
Nedlands, Western Australia, Australia, 6009
Contact: Anna Nowak, Site 0122    +61408818656      
Kepler Universitaetsklinikum Recruiting
Linz, Austria, 4020
Contact: Josef Pichler, Site 0062    +43505546228556      
Medical University Of Vienna Recruiting
Vienna, Austria, 1090
Contact: Matthias Preusser, Site 0061    +4314040044450      
Universitair Ziekenhuis Brussel Recruiting
Brussels, Belgium, 1090
Contact: Bart Neyns, Site 0070    +3224775457      
Cliniques Universitaires Saint-Luc Recruiting
Bruxelles, Belgium, 1200
Contact: Nicolas Whenham, Site 0069    +3210437147      
Uz Leuven Recruiting
Leuven, Belgium, 3000
Contact: Paul Clement, Site 0071    +3216346903      
Canada, British Columbia
British Columbia Cancer Agency-Vancouver Ctr Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Contact: Brian Thiessen, Site 0046    6048776000      
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Warren Mason, Site 0048    4165817823      
Canada, Quebec
Montreal Neurological Institute and Hospital Recruiting
Montreal, Quebec, Canada, H3A 2B4
Contact: Kevin Petrecca, Site 0047    5143982801      
Local Institution Recruiting
Copenhagen, Denmark, 2100
Contact: Site 0084         
Local Institution Recruiting
Odense, Denmark, 5000
Contact: Site 0085         
Local Institution Recruiting
Lille Cedex, France, 59037
Contact: Site 0043         
Local Institution Recruiting
Lyon Cedex 03, France, 69394
Contact: Site 0041         
Local Institution Recruiting
Marseille, France, 13385
Contact: Site 0040         
Local Institution Recruiting
Nancy, France, 54035
Contact: Site 0042         
Local Institution Recruiting
Paris cedex 13, France, 75651
Contact: Site 0039         
Local Institution Recruiting
Paris, France, 75010
Contact: Site 0038         
Local Institution Recruiting
Rennes Cedex, France, 35042
Contact: Site 0044         
Local Institution Recruiting
Toulouse, France, 31100
Contact: Site 0045         
Universitaetsklinikum Bonn Recruiting
Bonn, Germany, 53105
Contact: Ulrich Herrlinger, Site 0055    +4922828719887      
Uniklinik Erlangen Recruiting
Erlangen, Germany, 91054
Contact: Martin Uhl, Site 0123    +4991318534640      
Klinikum Der J. W. Goethe-Universitaet Frankfurt/Main Recruiting
Frankfurt Am Main, Germany, 60528
Contact: Oliver Baehr, Site 0053    +4969630187711      
Medizinische Universitaetsklinik Freiburg Recruiting
Freiburg, Germany, 79106
Contact: Oliver Schnell, Site 0124         
Universitaetsklinikum Hamburg Recruiting
Hamburg, Germany, 20246
Contact: Manfred Westphal, Site 0057    +4940741035316      
Universitaetsklinik Heidelberg Recruiting
Heidelberg, Germany, 69120
Contact: Antje Wick, Site 0056    +4962215638265      
Universitaetsklinik Koeln Recruiting
Koeln, Germany, 50937
Contact: Norbert Galldiks, Site 0131    +492214784015      
Universitaetsklinikum Muenster Recruiting
Muenster, Germany, 48149
Contact: Oliver Grauer, Site 0054    +492518346814      
Klinikum rechts der Isar der Technischen Universitat Munchen Recruiting
Munich, Germany, 81675
Contact: Stephanie Combs, Site 0130         
Bezirksklinikum Regensburg Recruiting
Regensburg, Germany, 93053
Contact: Peter Hau, Site 0058    +499419413290      
Universitasklinikum Tubingen Recruiting
Tuebingen, Germany, 72076
Contact: Ghazaleh Tabatabai, Site 0059    +491729031130      
Local Institution Recruiting
Petach Tikva, Israel, 49100
Contact: Site 0094         
Local Institution Recruiting
Tel Aviv, Israel, 64239
Contact: Site 0093         
Local Institution Recruiting
Bologna, Italy, 40139
Contact: Site 0088         
Local Institution Recruiting
Milano, Italy, 20133
Contact: Site 0089         
Local Institution Recruiting
Padova, Italy, 35128
Contact: Site 0092         
Local Institution Recruiting
Rozzano (milano), Italy, 20089
Contact: Site 0127         
Local Institution Recruiting
Siena, Italy, 53100
Contact: Site 0090         
Local Institution Recruiting
Torino, Italy, 10126
Contact: Site 0091         
Local Institution Recruiting
Nagoya-shi, Aichi, Japan, 4668560
Contact: Site 0110         
Local Institution Recruiting
Chiba-shi, Chiba, Japan, 2600856
Contact: Site 0099         
Local Institution Recruiting
Hiroshima-Shi, Hiroshima, Japan, 7348551
Contact: Site 0100         
Local Institution Recruiting
Sapporo-shi, Hokkaido, Japan, 0608648
Contact: Site 0101         
Local Institution Recruiting
Kobe-shi, Hyogo, Japan, 650-0017
Contact: Site 0105         
Local Institution Recruiting
Tsukuba-shi, Ibaraki, Japan, 3058576
Contact: Site 0116         
Local Institution Recruiting
Kanazawa-shi, Ishikawa, Japan, 9200934
Contact: Site 0103         
Local Institution Recruiting
Kagoshima-shi, Kagoshima, Japan, 8908520
Contact: Site 0102         
Local Institution Recruiting
Sagamihara-shi, Kanagawa, Japan, 2520375
Contact: Site 0118         
Local Institution Recruiting
Kumamoto-shi, Kumamoto, Japan, 8608556
Contact: Site 0106         
Local Institution Recruiting
Kyoto-shi, Kyoto, Japan, 6128555
Contact: Site 0108         
Local Institution Recruiting
Okayama-shi, Okayama, Japan, 7000914
Contact: Site 0120         
Local Institution Recruiting
Hirakata-shi, Osaka, Japan, 5731191
Contact: Site 0104         
Local Institution Recruiting
Suita-shi, Osaka, Japan, 5650871
Contact: Site 0112         
Local Institution Recruiting
Hidaka-shi, Saitama, Japan, 3501298
Contact: Site 0121         
Local Institution Recruiting
Bunkyo-ku, Tokyo, Japan, 1138655
Contact: Site 0114         
Local Institution Recruiting
Chuo-ku, Tokyo, Japan, 1040045
Contact: Site 0111         
Local Institution Recruiting
Mitaka-shi, Tokyo, Japan, 181-8611
Contact: Site 0107         
Local Institution Recruiting
Shinjuku-ku, Tokyo, Japan, 1628666
Contact: Site 0115         
Local Institution Recruiting
Yamagata-shi, Yamagata, Japan, 9909585
Contact: Site 0117         
Local Institution Recruiting
Kyoto, Japan, 6068507
Contact: Site 0109         
NKI AVL Recruiting
Amsterdam, Netherlands, 1066 CX
Contact: Dieta Brandsma, Site 0075    +31205122570      
Universitair Medisch Centrum Groningen Recruiting
Groningen, Netherlands, 9713 AP
Contact: Annemiek Walenkamp, Site 0074    +31503616161      
Erasmus Mc Recruiting
Rotterdam, Netherlands, 3015 CE
Contact: Martin Van Den Bent, Site 0073    +31107041415      
Universitair Medisch Centrum Utrecht Recruiting
Utrecht, Netherlands, 3584 CX
Contact: Filip De Vos, Site 0072    +31887556263      
Local Institution Recruiting
Oslo, Norway, 0424
Contact: Site 0083         
Uniwersyteckie Centrum Kliniczne Klinika Onkologii I Radiote Recruiting
Gdansk, Poland, 80-952
Contact: Renata Zaucha, Site 0086    +48583492257      
Local Institution Recruiting
Warszawa, Poland, 02-781
Contact: Site 0132         
Russian Federation
Local Institution Recruiting
Moscow, Russian Federation, 105229
Contact: Site 0095         
Local Institution Active, not recruiting
Moscow, Russian Federation, 115478
Local Institution Withdrawn
Moscow, Russian Federation, 125047
Local Institution Recruiting
Badalona-barcelona, Spain, 08916
Contact: Site 0126         
Local Institution Recruiting
Barcelona, Spain, 08035
Contact: Site 0078         
Local Institution Recruiting
Barcelona, Spain, 08036
Contact: Site 0125         
Local Institution Recruiting
Madrid, Spain, 28009
Contact: Site 0077         
Local Institution Recruiting
Madrid, Spain, 28041
Contact: Site 0076         
Local Institution Recruiting
Santiago Compostela, Spain, 15706
Contact: Site 0080         
Local Institution Recruiting
Valencia, Spain, 46014
Contact: Site 0079         
Local Institution Recruiting
Lund, Sweden, 221 85
Contact: Site 0081         
Local Institution Recruiting
Solna, Sweden, 171 64
Contact: Site 0082         
University Hospital Geneva Recruiting
Geneve, Switzerland, 1211
Contact: Pierre-Yves Dietrich, Site 0065    +41223729861      
Centre hospitalier universitaire Vaudois (CHUV) Recruiting
Lausanne, Switzerland, 1011
Contact: Andreas Hottinger, Site 0064    +41213140146      
UniversitaetsSpital Zurich Recruiting
Zuerich, Switzerland, 8091
Contact: Patrick Roth, Site 0063    +41442555543      
United Kingdom
University College Hospital Recruiting
London, Greater London, United Kingdom, NW1 2PG
Contact: Paul Mulholland, Site 0067    +444473809358      
Christie Hospital Nhs Found. Trust Recruiting
Manchester, Greater Manchester, United Kingdom, M20 4BX
Contact: Catherine Mcbain, Site 0066    +441614463000      
Royal Marsden Hospital Recruiting
Sutton, Surrey, United Kingdom, SM2 5PT
Contact: Frank Saran, Site 0119         
Beaston West of Scotland Cancer Centre Recruiting
Glasgow, United Kingdom, G12 0YN
Contact: Stefan Nowicki, Site 0068    +441413017000      
Sponsors and Collaborators
Bristol-Myers Squibb
Ono Pharmaceutical Co. Ltd
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

Additional Information:
Responsible Party: Bristol-Myers Squibb Identifier: NCT02667587     History of Changes
Other Study ID Numbers: CA209-548
2015-004722-34 ( EudraCT Number )
First Posted: January 29, 2016    Key Record Dates
Last Update Posted: May 8, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Brain Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action