Clinical trial NCT02667587: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Brain Neoplasms
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Ono Pharmaceutical Co. Ltd
First posted: 2016-01-29
Enrollment: 716
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-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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression-free Survival (PFS) Determined by BICR
timeFrame: From randomization to the date of the first documented tumor progression or death by any cause. (up to approximately 4.5 years)
measure: Overall Survival (OS)
timeFrame: From randomization to date of death (up to approximately 4.5 years)
Secondary outcomes:
measure: Overall Survival (OS) Rates at 12 Months
timeFrame: From randomization to 12 months after first dose
measure: Overall Survival (OS) Rates at 24 Months
timeFrame: From randomization to 24 months after first dose
measure: Progression Free Survival (PFS) Based on Investigator Assessment
timeFrame: From randomization to the date of the first documented tumor progression or death by any cause. (up to approximately 4.5 years)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Local Institution - 0023
state: Alabama
city: Phoenix
country: United States
facility: Local Institution - 0003
state: Arizona
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0010
state: California
city: Sacramento
country: United States
facility: Local Institution - 0128
state: California
city: San Diego
country: United States
facility: Local Institution - 0029
state: California
city: San Francisco
country: United States
facility: Local Institution - 0006
state: California
city: New Haven
country: United States
facility: Local Institution - 0004
state: Connecticut
city: Washington
country: United States
facility: Local Institution - 0031
state: District of Columbia
city: Miami
country: United States
facility: Local Institution - 0087
state: Florida
city: Tampa
country: United States
facility: Local Institution - 0030
state: Florida
city: Chicago
country: United States
facility: Local Institution - 0022
state: Illinois
city: Westwood
country: United States
facility: Local Institution - 0060
state: Kansas
city: Louisville
country: United States
facility: Local Institution - 0018
state: Kentucky
city: Baltimore
country: United States
facility: Local Institution - 0020
state: Maryland
city: Boston
country: United States
facility: Local Institution - 0011
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0028
state: Massachusetts
city: Detroit
country: United States
facility: Local Institution - 0035
state: Michigan
city: Saint Louis
country: United States
facility: Local Institution - 0002
state: Missouri
city: Edison
country: United States
facility: Local Institution - 0017
state: New Jersey
city: Hackensack
country: United States
facility: Local Institution - 0012
state: New Jersey
city: New York
country: United States
facility: Local Institution - 0015
state: New York
city: New York
country: United States
facility: Local Institution - 0024
state: New York
city: Charlotte
country: United States
facility: Local Institution - 0032
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 - 0001
state: Ohio
city: Columbus
country: United States
facility: Local Institution - 0027
state: Ohio
city: Allentown
country: United States
facility: Local Institution - 0098
state: Pennsylvania
city: Philadelphia
country: United States
facility: Local Institution - 0016
state: Pennsylvania
city: Charleston
country: United States
facility: Local Institution - 0021
state: South Carolina
city: Chattanooga
country: United States
facility: Erlanger Oncology & Hematology - Univ. of TN
state: Tennessee
city: Nashville
country: United States
facility: Local Institution - 0008
state: Tennessee
city: Dallas
country: United States
facility: Local Institution - 0025
state: Texas
city: Salt Lake City
country: United States
facility: Local Institution - 0009
state: Utah
city: Seattle
country: United States
facility: Local Institution - 0005
state: Washington
city: Liverpool
country: Australia
facility: Local Institution - 0049
state: New South Wales
city: St. Leonards
country: Australia
facility: Local Institution - 0052
state: New South Wales
city: Heidelberg
country: Australia
facility: Local Institution - 0050
state: Victoria
city: Prahran
country: Australia
facility: Local Institution - 0051
state: Victoria
city: Nedlands
country: Australia
facility: Local Institution - 0122
state: Western Australia
city: Linz
country: Austria
facility: Local Institution - 0062
city: Vienna
country: Austria
facility: Local Institution - 0061
city: Brussels
country: Belgium
facility: Local Institution - 0070
city: Bruxelles
country: Belgium
facility: Local Institution - 0069
city: Leuven
country: Belgium
facility: Local Institution - 0071
city: Vancouver
country: Canada
facility: Local Institution - 0046
state: British Columbia
city: Toronto
country: Canada
facility: Local Institution - 0048
state: Ontario
city: Montreal
country: Canada
facility: Local Institution - 0047
state: Quebec
city: Copenhagen
country: Denmark
facility: Local Institution - 0084
city: Odense
country: Denmark
facility: Local Institution - 0085
city: Lille Cedex
country: France
facility: Local Institution - 0043
city: Lyon Cedex 03
country: France
facility: Local Institution - 0041
city: Marseille
country: France
facility: Local Institution - 0040
city: Nancy
country: France
facility: Local Institution - 0042
city: Paris cedex 13
country: France
facility: Local Institution - 0039
city: Paris
country: France
facility: Local Institution - 0038
city: Rennes Cedex
country: France
facility: Local Institution - 0044
city: Toulouse
country: France
facility: Local Institution - 0045
city: Bonn
country: Germany
facility: Local Institution - 0055
city: Erlangen
country: Germany
facility: Local Institution - 0123
city: Frankfurt Am Main
country: Germany
facility: Local Institution - 0053
city: Freiburg
country: Germany
facility: Local Institution - 0124
city: Hamburg
country: Germany
facility: Local Institution - 0057
city: Heidelberg
country: Germany
facility: Local Institution - 0056
city: Koeln
country: Germany
facility: Local Institution - 0131
city: Muenster
country: Germany
facility: Local Institution - 0054
city: Munich
country: Germany
facility: Local Institution - 0130
city: Regensburg
country: Germany
facility: Local Institution - 0058
city: Tuebingen
country: Germany
facility: Local Institution - 0059
city: Petach Tikva
country: Israel
facility: Local Institution - 0094
city: Tel Aviv
country: Israel
facility: Local Institution - 0093
city: Bologna
country: Italy
facility: Local Institution - 0088
city: Milano
country: Italy
facility: Local Institution - 0089
city: Padova
country: Italy
facility: Local Institution - 0092
city: Rozzano (milano)
country: Italy
facility: Local Institution - 0127
city: Siena
country: Italy
facility: Local Institution - 0090
city: Torino
country: Italy
facility: Local Institution - 0091
city: Nagoya-shi
country: Japan
facility: Local Institution - 0110
state: Aichi
city: Chiba-shi
country: Japan
facility: Local Institution - 0099
state: Chiba
city: Hiroshima-Shi
country: Japan
facility: Local Institution - 0100
state: Hiroshima
city: Sapporo-shi
country: Japan
facility: Local Institution - 0101
state: Hokkaido
city: Kobe-shi
country: Japan
facility: Local Institution - 0105
state: Hyogo
city: Tsukuba-shi
country: Japan
facility: Local Institution - 0116
state: Ibaraki
city: Kanazawa-shi
country: Japan
facility: Local Institution - 0103
state: Ishikawa
city: Kagoshima-shi
country: Japan
facility: Local Institution - 0102
state: Kagoshima
city: Sagamihara-shi
country: Japan
facility: Local Institution - 0118
state: Kanagawa
city: Kumamoto-shi
country: Japan
facility: Local Institution - 0106
state: Kumamoto
city: Okayama-shi
country: Japan
facility: Local Institution - 0120
state: Okayama
city: Hirakata-shi
country: Japan
facility: Local Institution - 0104
state: Osaka
city: Suita
country: Japan
facility: Local Institution - 0112
state: Osaka
city: Hidaka-shi
country: Japan
facility: Local Institution - 0121
state: Saitama
city: Bunkyo-ku
country: Japan
facility: Local Institution - 0114
state: Tokyo
city: Chuo-ku
country: Japan
facility: Local Institution - 0111
state: Tokyo
city: Mitaka-shi
country: Japan
facility: Local Institution - 0107
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Local Institution - 0115
state: Tokyo
city: Yamagata-shi
country: Japan
facility: Local Institution - 0117
state: Yamagata
city: Kyoto
country: Japan
facility: Local Institution - 0109
city: Kyoto
country: Japan
facility: Local Institution - 0108
city: Rotterdam
country: Netherlands
facility: Local Institution - 0073
state: Zuid-Holland
city: Amsterdam
country: Netherlands
facility: Local Institution - 0075
city: Groningen
country: Netherlands
facility: Local Institution - 0074
city: Utrecht
country: Netherlands
facility: Local Institution - 0072
city: Oslo
country: Norway
facility: Local Institution - 0083
city: Gdansk
country: Poland
facility: Local Institution - 0086
city: Warszawa
country: Poland
facility: Local Institution - 0132
city: Moscow
country: Russian Federation
facility: Local Institution - 0095
city: Moscow
country: Russian Federation
facility: Local Institution - 0097
city: Badalona-barcelona
country: Spain
facility: Local Institution - 0126
city: Barcelona
country: Spain
facility: Local Institution - 0078
city: Barcelona
country: Spain
facility: Local Institution - 0125
city: Madrid
country: Spain
facility: Local Institution - 0077
city: Madrid
country: Spain
facility: Local Institution - 0076
city: Santiago Compostela
country: Spain
facility: Local Institution - 0080
city: Valencia
country: Spain
facility: Local Institution - 0079
city: Lund
country: Sweden
facility: Local Institution - 0081
city: Solna
country: Sweden
facility: Local Institution - 0082
city: Geneve
country: Switzerland
facility: Local Institution - 0065
city: Lausanne
country: Switzerland
facility: Local Institution - 0064
city: Zuerich
country: Switzerland
facility: Local Institution - 0063
city: Manchester
country: United Kingdom
facility: Local Institution - 0066
state: Greater Manchester
city: Sutton
country: United Kingdom
facility: Local Institution - 0119
state: Surrey
city: Glasgow
country: United Kingdom
facility: Local Institution - 0068
city: London
country: United Kingdom
facility: Local Institution - 0067
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Lim M, Weller M, Idbaih A, Steinbach J, Finocchiaro G, Raval RR, Ansstas G, Baehring J, Taylor JW, Honnorat J, Petrecca K, De Vos F, Wick A, Sumrall A, Sahebjam S, Mellinghoff IK, Kinoshita M, Roberts M, Slepetis R, Warad D, Leung D, Lee M, Reardon DA, Omuro A. Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Neuro Oncol. 2022 Nov 2;24(11):1935-1949. doi: 10.1093/neuonc/noac116.
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.