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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02667587




Registration number
NCT02667587
Ethics application status
Date submitted
26/01/2016
Date registered
29/01/2016
Date last updated
29/05/2024

Titles & IDs
Public title
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)
Scientific 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
Secondary ID [1] 0 0
2015-004722-34
Secondary ID [2] 0 0
CA209-548
Universal Trial Number (UTN)
Trial acronym
CheckMate548
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Brain Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
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

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
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) Determined by BICR
Timepoint [1] 0 0
From randomization to the date of the first documented tumor progression or death by any cause. (up to approximately 4.5 years)
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
From randomization to date of death (up to approximately 4.5 years)
Secondary outcome [1] 0 0
Overall Survival (OS) Rates at 12 Months
Timepoint [1] 0 0
From randomization to 12 months after first dose
Secondary outcome [2] 0 0
Overall Survival (OS) Rates at 24 Months
Timepoint [2] 0 0
From randomization to 24 months after first dose
Secondary outcome [3] 0 0
Progression Free Survival (PFS) Based on Investigator Assessment
Timepoint [3] 0 0
From randomization to the date of the first documented tumor progression or death by any cause. (up to approximately 4.5 years)

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



* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/05/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/04/2024
Sample size
Target
Accrual to date
Final
716
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
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Local Institution - 0049 - Liverpool
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Local Institution - 0052 - St. Leonards
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Local Institution - 0050 - Heidelberg
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Local Institution - 0051 - Prahran
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Local Institution - 0122 - Nedlands
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2170 - Liverpool
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2065 - St. Leonards
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3084 - Heidelberg
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3181 - Prahran
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bristol-Myers Squibb
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Ono Pharmaceutical Co. Ltd
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02667587
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02667587