Clinical trial NCT02617589: 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)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Brain Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Ono Pharmaceutical Co. Ltd
First posted: 2015-12-01
Enrollment: 560
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: up to 3 years
Secondary outcomes:
measure: Kaplan-Meier Plot of Progression Free Survival
timeFrame: From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 6 years)
measure: Overall Survival Rate at 24 Months
timeFrame: At 24 Months
measure: Overall Survival in Tumor Mutational Burden (TMB) High Population
timeFrame: From randomization to the date of death due to any cause (up to approximately 6 years)
measure: Progression Free Survival in Tumor Mutational Burden (TMB) High Population
timeFrame: From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 6 years)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Local Institution - 0083
state: Arizona
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0019
state: California
city: Sacramento
country: United States
facility: Sutter Institute For Medical Research
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: San Francisco
country: United States
facility: The Regents of the University of California, San Francisco
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Miami
country: United States
facility: University Of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University - Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: The University Of Chicago
state: Illinois
city: Westwood
country: United States
facility: University Of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University School Of Medicine
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Local Institution - 0006
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School OF Medicine-Siteman Cancer Center
state: Missouri
city: Edison
country: United States
facility: JFK Medical Center
state: New Jersey
city: Hackensack
country: United States
facility: Local Institution - 0064
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center (Cumc)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Preston Robert Tisch Brain Tumor Center at Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Local Institution - 0010
state: Ohio
city: Columbus
country: United States
facility: Local Institution - 0095
state: Ohio
city: Allentown
country: United States
facility: Local Institution - 0132
state: Pennsylvania
city: Philadelphia
country: United States
facility: Local Institution - 0007
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University Of South Carolina
state: South Carolina
city: Chattanooga
country: United States
facility: Local Institution - 0090
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University Of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: University Of Texas Md Anderson Cancer Ctr
state: Texas
city: Salt Lake City
country: United States
facility: Local Institution - 0068
state: Utah
city: Seattle
country: United States
facility: Swedish Neuroscience Institute
state: Washington
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Heidelberg
country: Australia
facility: Local Institution - 0003
state: Victoria
city: Prahran
country: Australia
facility: Local Institution - 0004
state: Victoria
city: Nedlands
country: Australia
facility: Local Institution - 0001
state: Western Australia
city: New South Wales
country: Australia
facility: Local Institution - 0002
city: Linz
country: Austria
facility: Local Institution - 0061
city: Vienna
country: Austria
facility: Local Institution - 0060
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: Uz Leuven
city: Vancouver
country: Canada
facility: BC Cancer - Vancouver
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Copenhagen
country: Denmark
facility: Local Institution
city: Odense
country: Denmark
facility: Local Institution
city: Bron Cedex
country: France
facility: Local Institution - 0032
city: Lille Cedex
country: France
facility: Local Institution
city: Marseille
country: France
facility: Local Institution - 0024
city: Nancy
country: France
facility: Local Institution - 0101
city: Paris cedex 13
country: France
facility: Local Institution - 0038
city: Paris
country: France
facility: Local Institution - 0023
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Toulouse
country: France
facility: Local Institution - 0106
city: Bonn
country: Germany
facility: Local Institution - 0051
city: Erlangen
country: Germany
facility: Local Institution - 0072
city: Frankfurt am Main
country: Germany
facility: Local Institution - 0049
city: Freiburg
country: Germany
facility: Local Institution - 0073
city: Hamburg
country: Germany
facility: Local Institution - 0054
city: Heidelberg
country: Germany
facility: Local Institution - 0052
city: Koeln
country: Germany
facility: Local Institution - 0139
city: Muenster
country: Germany
facility: Local Institution - 0050
city: Munich
country: Germany
facility: Local Institution - 0138
city: Regensburg
country: Germany
facility: Local Institution - 0055
city: Tuebingen
country: Germany
facility: Local Institution - 0056
city: Petach Tikva
country: Israel
facility: Local Institution - 0096
city: Tel Aviv
country: Israel
facility: Local Institution - 0097
city: Bologna
country: Italy
facility: Local Institution - 0076
city: Milano
country: Italy
facility: Local Institution - 0079
city: Padova
country: Italy
facility: Local Institution - 0126
city: Rozzano (milano)
country: Italy
facility: Local Institution - 0135
city: Siena
country: Italy
facility: Local Institution - 0078
city: Torino
country: Italy
facility: Local Institution - 0077
city: Nagoya-shi
country: Japan
facility: Local Institution - 0115
state: Aichi
city: Chiba-shi
country: Japan
facility: Local Institution - 0125
state: Chiba
city: Hiroshima-Shi
country: Japan
facility: Local Institution - 0123
state: Hiroshima
city: Sapporo-shi
country: Japan
facility: Local Institution - 0122
state: Hokkaido
city: Kobe
country: Japan
facility: Local Institution - 0129
state: Hyogo
city: Tsukuba-shi
country: Japan
facility: Local Institution - 0111
state: Ibaraki
city: Kanazawa-shi
country: Japan
facility: Local Institution - 0121
state: Ishikawa
city: Kagoshima-shi
country: Japan
facility: Local Institution - 0131
state: Kagoshima
city: Sagamihara-shi
country: Japan
facility: Local Institution - 0133
state: Kanagawa
city: Kumamoto-shi
country: Japan
facility: Local Institution - 0119
state: Kumamoto
city: Kyoto-shi
country: Japan
facility: Local Institution - 0117
state: Kyoto
city: Kyoto-shi
country: Japan
facility: Local Institution - 0116
state: Kyoto
city: Okayama-shi
country: Japan
facility: Local Institution - 0134
state: Okayama
city: Hirakata-shi
country: Japan
facility: Local Institution
state: Osaka
city: Suita-shi
country: Japan
facility: Local Institution - 0130
state: Osaka
city: Hidaka
country: Japan
facility: Local Institution - 0113
state: Saitama
city: Bunkyo-ku
country: Japan
facility: Local Institution - 0128
state: Tokyo
city: Chuo-ku
country: Japan
facility: Local Institution - 0114
state: Tokyo
city: Mitaka-shi
country: Japan
facility: Local Institution - 0118
state: Tokyo
city: Yamagata-shi
country: Japan
facility: Local Institution - 0110
state: Yamagata
city: Tokyo
country: Japan
facility: Local Institution - 0112
city: Amsterdam
country: Netherlands
facility: NKI AVL
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Rotterdam
country: Netherlands
facility: Erasmus Mc
city: Utrecht
country: Netherlands
facility: Local Institution - 0063
city: Oslo
country: Norway
facility: Local Institution
city: Gdansk
country: Poland
facility: Local Institution - 0080
city: Warszawa
country: Poland
facility: Local Institution - 0081
city: Moscow
country: Russian Federation
facility: Local Institution - 0070
city: Moscow
country: Russian Federation
facility: Local Institution - 0105
city: Badalona-Barcelona
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution - 0028
city: Madrid
country: Spain
facility: Local Institution - 0029
city: Madrid
country: Spain
facility: Local Institution
city: Santiago De Compostela
country: Spain
facility: Local Institution
city: Valencia
country: Spain
facility: Local Institution - 0025
city: Lund
country: Sweden
facility: Local Institution
city: Solna
country: Sweden
facility: Local Institution
city: Geneve
country: Switzerland
facility: Local Institution - 0059
city: Lausanne
country: Switzerland
facility: Local Institution - 0057
city: Zuerich
country: Switzerland
facility: Local Institution - 0053
city: London
country: United Kingdom
facility: University College Hospital
state: Greater London
city: Manchester
country: United Kingdom
facility: Christie Hospital Nhs Found. Trust
state: Greater Manchester
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
state: Surrey
city: Glasgow
country: United Kingdom
facility: Beaston West of Scotland Cancer Centre
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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. No abstract available.