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)
- Conditions
- Brain Neoplasms
- Interventions
- Registration Number
- NCT02667587
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 716
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Nivolumab + Temozolomide + Radiotherapy 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 Nivolumab placebo + Temozolomide + Radiotherapy Nivolumab Placebo 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 Nivolumab placebo + Temozolomide + Radiotherapy 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 Nivolumab + Temozolomide + Radiotherapy Nivolumab 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 Nivolumab + Temozolomide + Radiotherapy Temozolomide 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 Nivolumab placebo + Temozolomide + Radiotherapy Temozolomide 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
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) Determined by BICR From randomization to the date of the first documented tumor progression or death by any cause. (up to approximately 4.5 years) The time from randomization to the date of the first documented tumor progression or death by any cause. PFS will be determined by a Blinded Independent Central Review (BICR) assessed based on Radiologic Assessment in Neuro-Oncology (RANO) criteria. Specifically, RANO response criteria indicates that within the first 12 weeks of completion of radiotherapy, progression can only be assessed if the majority of the new enhancement is outside of the radiation field or if there is pathologic confirmation of progressive disease.
Overall Survival (OS) From randomization to date of death (up to approximately 4.5 years) The time from the date of randomization to the date of death. who have not died by the end of the study will be censored to last known date alive. OS is assessed in the randomized population with no corticosteroids at baseline population and in the overall randomized population.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Rates at 24 Months From randomization to 24 months after first dose Overall Survival (OS) rate is defined as the percentage of participants surviving at 24 months
Overall Survival (OS) Rates at 12 Months From randomization to 12 months after first dose Overall Survival (OS) rate is defined as the percentage of participants surviving at 12 months
Progression Free Survival (PFS) Based on Investigator Assessment From randomization to the date of the first documented tumor progression or death by any cause. (up to approximately 4.5 years) The time from randomization to the date of the first documented tumor progression or death by any cause. PFS will be determined by investigator assessment based Radiologic Assessment in Neuro-Oncology (RANO) criteria. Specifically, RANO response criteria indicates that within the first 12 weeks of completion of radiotherapy, progression can only be assessed if the majority of the new enhancement is outside of the radiation field or if there is pathologic confirmation of progressive disease.
Trial Locations
- Locations (123)
Local Institution - 0028
🇺🇸Boston, Massachusetts, United States
Local Institution - 0010
🇺🇸Los Angeles, California, United States
Local Institution - 0128
🇺🇸Sacramento, California, United States
Local Institution - 0022
🇺🇸Chicago, Illinois, United States
Local Institution - 0030
🇺🇸Tampa, Florida, United States
Local Institution - 0018
🇺🇸Louisville, Kentucky, United States
Local Institution - 0060
🇺🇸Westwood, Kansas, United States
Local Institution - 0020
🇺🇸Baltimore, Maryland, United States
Local Institution - 0002
🇺🇸Saint Louis, Missouri, United States
Local Institution - 0024
🇺🇸New York, New York, United States
Local Institution - 0015
🇺🇸New York, New York, United States
Local Institution - 0032
🇺🇸Charlotte, North Carolina, United States
Local Institution - 0001
🇺🇸Cleveland, Ohio, United States
Local Institution - 0027
🇺🇸Columbus, Ohio, United States
Local Institution - 0016
🇺🇸Philadelphia, Pennsylvania, United States
Local Institution - 0098
🇺🇸Allentown, Pennsylvania, United States
Local Institution - 0021
🇺🇸Charleston, South Carolina, United States
Erlanger Oncology & Hematology - Univ. of TN
🇺🇸Chattanooga, Tennessee, United States
Local Institution - 0025
🇺🇸Dallas, Texas, United States
Local Institution - 0049
🇦🇺Liverpool, New South Wales, Australia
Local Institution - 0052
🇦🇺St. Leonards, New South Wales, Australia
Local Institution - 0050
🇦🇺Heidelberg, Victoria, Australia
Local Institution - 0122
🇦🇺Nedlands, Western Australia, Australia
Local Institution - 0070
🇧🇪Brussels, Belgium
Local Institution - 0069
🇧🇪Bruxelles, Belgium
Local Institution - 0048
🇨🇦Toronto, Ontario, Canada
Local Institution - 0043
🇫🇷Lille Cedex, France
Local Institution - 0040
🇫🇷Marseille, France
Local Institution - 0042
🇫🇷Nancy, France
Local Institution - 0045
🇫🇷Toulouse, France
Local Institution - 0038
🇫🇷Paris, France
Local Institution - 0055
🇩🇪Bonn, Germany
Local Institution - 0053
🇩🇪Frankfurt Am Main, Germany
Local Institution - 0123
🇩🇪Erlangen, Germany
Local Institution - 0124
🇩🇪Freiburg, Germany
Local Institution - 0054
🇩🇪Muenster, Germany
Local Institution - 0057
🇩🇪Hamburg, Germany
Local Institution - 0056
🇩🇪Heidelberg, Germany
Local Institution - 0059
🇩🇪Tuebingen, Germany
Local Institution - 0058
🇩🇪Regensburg, Germany
Local Institution - 0130
🇩🇪Munich, Germany
Local Institution - 0093
🇮🇱Tel Aviv, Israel
Local Institution - 0088
🇮🇹Bologna, Italy
Local Institution - 0092
🇮🇹Padova, Italy
Local Institution - 0090
🇮🇹Siena, Italy
Local Institution - 0110
🇯🇵Nagoya-shi, Aichi, Japan
Local Institution - 0102
🇯🇵Kagoshima-shi, Kagoshima, Japan
Local Institution - 0103
🇯🇵Kanazawa-shi, Ishikawa, Japan
Local Institution - 0118
🇯🇵Sagamihara-shi, Kanagawa, Japan
Local Institution - 0106
🇯🇵Kumamoto-shi, Kumamoto, Japan
Local Institution - 0109
🇯🇵Kyoto, Japan
Local Institution - 0086
🇵🇱Gdansk, Poland
Local Institution - 0074
🇳🇱Groningen, Netherlands
Local Institution - 0083
🇳🇴Oslo, Norway
Local Institution - 0078
🇪🇸Barcelona, Spain
Local Institution - 0126
🇪🇸Badalona-barcelona, Spain
Local Institution - 0081
🇸🇪Lund, Sweden
Local Institution - 0077
🇪🇸Madrid, Spain
Local Institution - 0125
🇪🇸Barcelona, Spain
Local Institution - 0076
🇪🇸Madrid, Spain
Local Institution - 0079
🇪🇸Valencia, Spain
Local Institution - 0080
🇪🇸Santiago Compostela, Spain
Local Institution - 0065
🇨🇭Geneve, Switzerland
Local Institution - 0119
🇬🇧Sutton, Surrey, United Kingdom
Local Institution - 0066
🇬🇧Manchester, Greater Manchester, United Kingdom
Local Institution - 0068
🇬🇧Glasgow, United Kingdom
Local Institution - 0067
🇬🇧London, United Kingdom
Local Institution - 0029
🇺🇸San Diego, California, United States
Local Institution - 0005
🇺🇸Seattle, Washington, United States
Local Institution - 0006
🇺🇸San Francisco, California, United States
Local Institution - 0087
🇺🇸Miami, Florida, United States
Preston Robert Tisch Brain Tumor Center at Duke University
🇺🇸Durham, North Carolina, United States
Local Institution - 0009
🇺🇸Salt Lake City, Utah, United States
Local Institution - 0003
🇺🇸Phoenix, Arizona, United States
Local Institution - 0035
🇺🇸Detroit, Michigan, United States
Local Institution - 0061
🇦🇹Vienna, Austria
Local Institution - 0094
🇮🇱Petach Tikva, Israel
Local Institution - 0100
🇯🇵Hiroshima-Shi, Hiroshima, Japan
Local Institution - 0120
🇯🇵Okayama-shi, Okayama, Japan
Local Institution - 0004
🇺🇸New Haven, Connecticut, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Local Institution - 0011
🇺🇸Boston, Massachusetts, United States
Local Institution - 0017
🇺🇸Edison, New Jersey, United States
Local Institution - 0031
🇺🇸Washington, District of Columbia, United States
Local Institution - 0062
🇦🇹Linz, Austria
Local Institution - 0071
🇧🇪Leuven, Belgium
Local Institution - 0105
🇯🇵Kobe-shi, Hyogo, Japan
Local Institution - 0116
🇯🇵Tsukuba-shi, Ibaraki, Japan
Local Institution - 0108
🇯🇵Kyoto, Japan
Local Institution - 0008
🇺🇸Nashville, Tennessee, United States
Local Institution - 0012
🇺🇸Hackensack, New Jersey, United States
Local Institution - 0115
🇯🇵Shinjuku-ku, Tokyo, Japan
Local Institution - 0051
🇦🇺Prahran, Victoria, Australia
Local Institution - 0099
🇯🇵Chiba-shi, Chiba, Japan
Local Institution - 0112
🇯🇵Suita, Osaka, Japan
Local Institution - 0117
🇯🇵Yamagata-shi, Yamagata, Japan
Local Institution - 0075
🇳🇱Amsterdam, Netherlands
Local Institution - 0072
🇳🇱Utrecht, Netherlands
Local Institution - 0132
🇵🇱Warszawa, Poland
Local Institution - 0063
🇨🇭Zuerich, Switzerland
Local Institution - 0046
🇨🇦Vancouver, British Columbia, Canada
Local Institution - 0095
🇷🇺Moscow, Russian Federation
Local Institution - 0047
🇨🇦Montreal, Quebec, Canada
Local Institution - 0121
🇯🇵Hidaka-shi, Saitama, Japan
Local Institution - 0101
🇯🇵Sapporo-shi, Hokkaido, Japan
Local Institution - 0104
🇯🇵Hirakata-shi, Osaka, Japan
Local Institution - 0064
🇨🇭Lausanne, Switzerland
Local Institution - 0107
🇯🇵Mitaka-shi, Tokyo, Japan
Local Institution - 0114
🇯🇵Bunkyo-ku, Tokyo, Japan
Local Institution - 0111
🇯🇵Chuo-ku, Tokyo, Japan
Local Institution - 0073
🇳🇱Rotterdam, Zuid-Holland, Netherlands
Local Institution - 0097
🇷🇺Moscow, Russian Federation
Local Institution - 0085
🇩🇰Odense, Denmark
Local Institution - 0084
🇩🇰Copenhagen, Denmark
Local Institution - 0089
🇮🇹Milano, Italy
Local Institution - 0127
🇮🇹Rozzano (milano), Italy
Local Institution - 0091
🇮🇹Torino, Italy
Local Institution - 0023
🇺🇸Birmingham, Alabama, United States
Local Institution - 0041
🇫🇷Lyon Cedex 03, France
Local Institution - 0039
🇫🇷Paris cedex 13, France
Local Institution - 0044
🇫🇷Rennes Cedex, France
Local Institution - 0082
🇸🇪Solna, Sweden
Local Institution - 0131
🇩🇪Koeln, Germany