Clinical trial NCT02017717: A Study of the Effectiveness and Safety of Nivolumab Compared to Bevacizumab and of Nivolumab With or Without Ipilimumab in Glioblastoma Patients
Official title: A Randomized Phase 3 Open Label Study of Nivolumab Versus Bevacizumab and Multiple Phase 1 Safety Cohorts of Nivolumab or Nivolumab in Combination With Ipilimumab Across Different Lines of Glioblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Recurrent Glioblastoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2013-12-23
Enrollment: 529
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 the study is to compare the efficacy and safety of nivolumab administered alone versus bevacizumab in patients diagnosed with recurrent glioblastoma (a type of brain cancer, also known as GBM), and to evaluate the safety and tolerability of nivolumab administered alone or in combination with ipilimumab in patients with different lines of GBM therapy.

Detailed description: Allocation: Randomized (Cohorts 1, 2 and Part B of 1c/1d), Non-Randomized (Cohorts 1b, and Part A of 1c/1d)

Eligibility criteria: Inclusion Criteria:

* Participants with histologically confirmed Grade IV malignant glioma
* Previous treatment with radiotherapy and temozolomide (Cohorts 1, 1b and 2 only)
* First recurrence of GBM (Cohorts 1, 1b and 2 only)
* First diagnosis of GBM with resectable disease (Cohorts 1c Part A only)
* First diagnosis of unmethylated MGMT GBM (Cohort 1d and Cohort 1c Part B only)
* Karnofsky performance score of 70 or higher

Exclusion Criteria:

* More than 1 recurrence of GBM (Cohorts 1, 1b and 2 only)
* Any recurrence of GBM (Cohorts 1c and 1d only)
* Presence of extracranial metastatic or leptomeningeal disease
* Active, known or suspected autoimmune disease
* Clinically significant cardiovascular disease
* Prior bevacizumab or other Vascular Endothelial Growth Factor (VEGF) or anti-angiogenic treatment (Cohort 2 only)

Primary outcomes:
measure: Percentage of Participants With Drug-Related Adverse Events Leading to Discontinuation by Worst CTC Grade for All Treated Participants in Cohorts 1, 1b, 1c and 1d Who Permanently Discontinued Study Medication Prior to Completing Four Doses
timeFrame: Includes events reported between first dose and 30 days after last dose of study therapy (up to 3 doses, up to approximately 2 months)
measure: Percentage of Participants With Adverse Events (Worst Grade) in Cohorts 1, 1b, 1c and 1d
timeFrame: From first dose to 30 days post last dose (up to approximately 34 months).
measure: Percentage of Participants With Serious Adverse Events (Worst Grade) in Cohorts 1, 1b, 1c and 1d
timeFrame: From first dose to 30 days post last dose (up to approximately 34 months).
measure: Percentage of Participants With Specific Laboratory Abnormalities in Liver Tests in Cohorts 1, 1b, 1c and 1d
timeFrame: From first dose to 30 days post last dose (up to approximately 34 months).
measure: Percentage of Participants With Specific Laboratory Abnormalities in Thyroid Tests in Cohorts 1, 1b, 1c and 1d
timeFrame: From first dose to 30 days post last dose (up to approximately 34 months).
measure: Overall Survival (OS) for Cohort 2
timeFrame: Time between the date of randomization and the date of death due to any cause (up to up to 17Jun2019, approximately 5 years)
Secondary outcomes:
measure: Overall Survival (OS) at 12 Months for Cohort 2
timeFrame: From randomization to 12 months following randomization
measure: Overall Survival (OS) for Cohorts 1c and 1d
timeFrame: Time between the date of randomization and the date of death due to any cause (up to approximately 10 years and 5 months)
measure: Progression Free Survival (PFS) for Cohort 2
timeFrame: Time from randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 10 years and 5 months)
measure: Objective Response Rate (ORR) for Cohort 2
timeFrame: Time from randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 10 years and 5 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0055
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0009
state: California
city: Los Angeles
country: United States
facility: UCLA Neuro-Oncology Program
state: California
city: San Francisco
country: United States
facility: Local Institution - 0014
state: California
city: San Francisco
country: United States
facility: The Regents of the University of California, San Francisco
state: California
city: Aurora
country: United States
facility: Anschutz Cancer Pavilion
state: Colorado
city: Aurora
country: United States
facility: Local Institution - 0021
state: Colorado
city: New Haven
country: United States
facility: Local Institution - 0001
state: Connecticut
city: New Haven
country: United States
facility: Yale University School Of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Local Institution - 0002
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins University School Of Medicine
state: Maryland
city: Baltimore
country: United States
facility: Local Institution - 0008
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Med Ctr
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0006
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0043
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0056
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Local Institution - 0003
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: Local Institution - 0007
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 - 0049
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University - Clinical Research Institute
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Charleston
country: United States
facility: Local Institution - 0023
state: South Carolina
city: Charleston
country: United States
facility: Medical University Of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Local Institution - 0005
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Local Institution - 0024
state: Texas
city: Houston
country: United States
facility: University Of Texas Md Anderson Cancer Ctr
state: Texas
city: Charlottesville
country: United States
facility: University Of Virginia Health System
state: Virginia
city: Seattle
country: United States
facility: University of Washington - Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: Local Institution - 0020
state: Washington
city: Seattle
country: United States
facility: Swedish Neuroscience Institute
state: Washington
city: Liverpool
country: Australia
facility: Local Institution - 0035
state: New South Wales
city: Liverpool
country: Australia
facility: Local Institution
state: New South Wales
city: East Bentleigh
country: Australia
facility: Local Institution - 0034
state: Victoria
city: East Bentleigh
country: Australia
facility: Local Institution
state: Victoria
city: Heidelberg
country: Australia
facility: Local Institution - 0033
state: Victoria
city: Heidelberg
country: Australia
facility: Local Institution
state: Victoria
city: Nedlands
country: Australia
facility: Local Institution - 0032
state: Western Australia
city: Nedlands
country: Australia
facility: Local Institution
state: Western Australia
city: Brussels
country: Belgium
facility: Local Institution - 0050
city: Brussels
country: Belgium
facility: Local Institution
city: Bruxelles
country: Belgium
facility: Local Institution - 0051
city: Bruxelles
country: Belgium
facility: Local Institution
city: Aarhus C
country: Denmark
facility: Aarhus University Hospital
city: Aarhus C
country: Denmark
facility: Local Institution - 0058
city: Odense C
country: Denmark
facility: Local Institution - 0057
city: Odense C
country: Denmark
facility: Odense University Hospital
city: Bron cedex
country: France
facility: Local Institution - 0062
city: Bron cedex
country: France
facility: Local Institution
city: Marseille Cedex 5
country: France
facility: Local Institution - 0063
city: Marseille Cedex 5
country: France
facility: Local Institution
city: Paris cedex 13
country: France
facility: Local Institution - 0064
city: Paris cedex 13
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution - 0068
city: Paris
country: France
facility: Local Institution
city: Bonn
country: Germany
facility: Local Institution - 0037
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn
city: Frankfurt Am Main
country: Germany
facility: Klinikum Der J. W. Goethe-Universitaet Frankfurt/Main
city: Frankfurt Am Main
country: Germany
facility: Local Institution - 0036
city: Heidelberg
country: Germany
facility: Local Institution - 0038
city: Heidelberg
country: Germany
facility: Local Institution
city: Muenster
country: Germany
facility: Local Institution - 0041
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster
city: Bologna
country: Italy
facility: Local Institution - 0010
city: Bologna
country: Italy
facility: Local Institution
city: Milano
country: Italy
facility: Local Institution - 0011
city: Milano
country: Italy
facility: Local Institution
city: Siena
country: Italy
facility: Local Institution - 0012
city: Siena
country: Italy
facility: Local Institution
city: Torino
country: Italy
facility: Azienda Ospedaliera Citta della Salute e della Scienza
city: Torino
country: Italy
facility: Local Institution - 0013
city: Amsterdam
country: Netherlands
facility: Local Institution - 0067
city: Amsterdam
country: Netherlands
facility: Local Institution
city: Groningen
country: Netherlands
facility: Local Institution - 0066
city: Groningen
country: Netherlands
facility: Local Institution
city: Gdansk
country: Poland
facility: Local Institution - 0060
city: Gdansk
country: Poland
facility: Local Institution
city: Warszawa
country: Poland
facility: Local Institution - 0059
city: Warszawa
country: Poland
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution - 0047
city: Barcelona
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution - 0045
city: Madrid
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution - 0046
city: Madrid
country: Spain
facility: Local Institution
city: Pamplona
country: Spain
facility: Local Institution - 0070
city: Pamplona
country: Spain
facility: Local Institution
city: Lausanne
country: Switzerland
facility: Centre hospitalier universitaire Vaudois (CHUV)
city: Lausanne
country: Switzerland
facility: Local Institution - 0039
city: Zuerich
country: Switzerland
facility: Local Institution - 0040
city: Zuerich
country: Switzerland
facility: UniversitaetsSpital Zurich
city: London
country: United Kingdom
facility: Local Institution - 0018
state: Greater London
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
city: Manchester
country: United Kingdom
facility: Local Institution - 0015
state: Greater Manchester
city: Manchester
country: United Kingdom
facility: Local Institution
state: Greater Manchester
city: Liverpool
country: United Kingdom
facility: Local Institution - 0017
city: Liverpool
country: United Kingdom
facility: Local Institution
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.
citation: Reardon DA, Brandes AA, Omuro A, Mulholland P, Lim M, Wick A, Baehring J, Ahluwalia MS, Roth P, Bahr O, Phuphanich S, Sepulveda JM, De Souza P, Sahebjam S, Carleton M, Tatsuoka K, Taitt C, Zwirtes R, Sampson J, Weller M. Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma: The CheckMate 143 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Jul 1;6(7):1003-1010. doi: 10.1001/jamaoncol.2020.1024.
citation: Stupp R. Drug development for glioma: are we repeating the same mistakes? Lancet Oncol. 2019 Jan;20(1):10-12. doi: 10.1016/S1470-2045(18)30827-1. Epub 2018 Dec 3. No abstract available.