Testing the Use of the Immunotherapy Drugs Ipilimumab and Nivolumab Plus Radiation Therapy Compared to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed MGMT Unmethylated Glioblastoma

A Randomized Phase II/III Open-Label Study of Ipilimumab and Nivolumab Versus Temozolomide in Patients With Newly Diagnosed MGMT (Tumor O-6-Methylguanine DNA Methyltransferase) Unmethylated Glioblastoma

This phase II/III trial compares the usual treatment with radiation therapy and temozolomide to radiation therapy in combination with immunotherapy with ipilimumab and nivolumab in treating patients with newly diagnosed MGMT unmethylated glioblastoma. Radiation therapy uses high energy photons to kill tumor and shrink tumors. Chemotherapy drugs, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Temozolomide, may not work as well for the treatment of tumors that have the unmethylated MGMT. Immunotherapy with monoclonal antibodies called immune checkpoint inhibitors, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is possible that immune checkpoint inhibitors may work better at time of first diagnosis as opposed to when tumor comes back. Giving radiation therapy with ipilimumab and nivolumab may lengthen the time without brain tumor returning or growing and may extend patients' life compared to usual treatment with radiation therapy and temozolomide.

Study Overview

• Status: Completed
• Conditions: Gliosarcoma; MGMT-Unmethylated Glioblastoma
• Intervention / Treatment: Biological: Nivolumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Biological: Ipilimumab; Radiation: Radiation Therapy; Drug: Temozolomide; Device: NovoTTF-100A Device; Procedure: Contrast-enhanced Magnetic Resonance Imaging

Detailed Description

PRIMARY OBJECTIVES:

I. To determine if adding ipilimumab and nivolumab to radiotherapy significantly prolongs progression-free survival (PFS) versus adding temozolomide to radiotherapy in patients with newly diagnosed glioblastoma (GBM) without MGMT promoter methylation. (Phase II) II. To determine if adding ipilimumab and nivolumab to radiotherapy significantly prolongs overall survival (OS) versus adding temozolomide to radiotherapy in patients with newly diagnosed GBM without MGMT promoter methylation. (Phase III)

SECONDARY OBJECTIVES:

I. To determine if adding ipilimumab and nivolumab to radiotherapy significantly prolongs PFS versus adding temozolomide to radiotherapy in patients with newly diagnosed GBM without MGMT promoter methylation for the phase III part of the study.

II. To determine if adding ipilimumab and nivolumab to radiotherapy significantly increases the 2-year OS rate versus adding temozolomide to radiotherapy in patients with newly diagnosed GBM without MGMT promoter methylation.

III. To evaluate the safety of adding ipilimumab and nivolumab to radiotherapy via comparative frequency between arms of specific adverse events of interest and frequency summaries for all adverse event types.

IV. To evaluate the effect of adding ipilimumab and nivolumab to radiotherapy versus adding temozolomide to radiotherapy on patient reported outcomes (PROs), as measured by the MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) in patients with newly diagnosed GBM without MGMT promoter methylation.

V. To evaluate the effect of adding ipilimumab and nivolumab to radiotherapy versus adding temozolomide to radiotherapy on selected Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) items in patients with newly diagnosed GBM without MGMT promoter methylation.

VI. To evaluate the impact of adding ipilimumab and nivolumab to radiotherapy versus adding temozolomide to radiotherapy on neurocognitive function (NCF) in patients with newly diagnosed GBM without MGMT promoter methylation.

EXPLORATORY OBJECTIVES:

I. To explore biomarkers in pre-treatment archival tumor tissue that may predict efficacy of ipilimumab and nivolumab as measured by OS, PFS, and 2-year OS rate, such as but not limited to:

Ia. PDL1 expression; Ib. Mutational burden. II. To explore (in the two treatment separately) whether the MGMT protein expression correlates with clinical outcomes including OS, PFS, and 2-year OS rate.

III. To evaluate if MGMT protein expression may be predictive of differential treatment effects between the two treatment arms.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks and simultaneously receive temozolomide orally (PO) daily for 6 weeks. After radiation, patients may wear the Optune device at the discretion of the patient and their treating physician. Beginning 1 month after radiation therapy, patients receive temozolomide on days 1-5. Treatment repeats every 28 days for up to 12 cycles at the discretion of the treating investigator in the absence of disease progression or unacceptable toxicity. Patients also undergo contrast-enhanced brain magnetic resonance imaging (MRI) throughout the trial.

ARM 2: Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks. Starting on the first day of radiation, patients also receive ipilimumab intravenously (IV) over 90 minutes once every 4 weeks (Q4W) for 4 doses and nivolumab IV over 30 minutes every 2 weeks until disease progression. Patients also undergo contrast-enhanced brain MRI throughout the trial.

After completion of study treatment, patients are followed up every 3 months for year 1, then every 4 months for year 2, and then every 6 months thereafter.

• Study Type: Interventional
• Enrollment (Actual): 159
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Anaheim, California, United States, 92806
      • Kaiser Permanente-Anaheim
    • Auburn, California, United States, 95602
      • Sutter Auburn Faith Hospital
    • Auburn, California, United States, 95603
      • Sutter Cancer Centers Radiation Oncology Services-Auburn
    • Concord, California, United States, 94520
      • John Muir Medical Center-Concord
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles Medical Center
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Ontario, California, United States, 91761
      • Kaiser Permanente-Ontario
    • Orange, California, United States, 92868
      • UC Irvine Health/Chao Family Comprehensive Cancer Center
    • Roseville, California, United States, 95661
      • Sutter Cancer Centers Radiation Oncology Services-Roseville
    • Roseville, California, United States, 95661
      • Sutter Roseville Medical Center
    • Sacramento, California, United States, 95816
      • Sutter Medical Center Sacramento
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • Torrance, California, United States, 90509
      • Torrance Memorial Medical Center
    • Torrance, California, United States, 90505
      • Torrance Memorial Physician Network - Cancer Care
    • Walnut Creek, California, United States, 94598
      • John Muir Medical Center-Walnut Creek
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Denver, Colorado, United States, 80210
      • AdventHealth Porter
    • Littleton, Colorado, United States, 80122
      • AdventHealth Littleton
    • Parker, Colorado, United States, 80138
      • AdventHealth Parker
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Millville, Delaware, United States, 19967
      • Beebe South Coastal Health Campus
    • Newark, Delaware, United States, 19713
      • Helen F Graham Cancer Center
    • Newark, Delaware, United States, 19713
      • Delaware Clinical and Laboratory Physicians PA
    • Newark, Delaware, United States, 19713
      • Medical Oncology Hematology Consultants PA
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
    • Rehoboth Beach, Delaware, United States, 19971
      • Beebe Health Campus
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson Cancer Center
    • Orlando, Florida, United States, 32803
      • AdventHealth Orlando
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University Medical Center
    • Savannah, Georgia, United States, 31405
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center
    • Thomasville, Georgia, United States, 31792
      • Lewis Hall Singletary Oncology Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96817
      • The Cancer Center of Hawaii-Liliha
    • Honolulu, Hawaii, United States, 96813
      • Hawaii Cancer Care Inc - Waterfront Plaza
    • Honolulu, Hawaii, United States, 96813
      • Queen's Cancer Cenrer - POB I
    • Honolulu, Hawaii, United States, 96813
      • Straub Clinic and Hospital
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii Cancer Center
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Cancer Care Inc-Liliha
    • Honolulu, Hawaii, United States, 96817
      • Queen's Cancer Center - Kuakini
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
    • Honolulu, Hawaii, United States, 96813
      • Island Urology
    • Kailua, Hawaii, United States, 96734
      • Castle Medical Center
    • Lihue, Hawaii, United States, 96766
      • Wilcox Memorial Hospital and Kauai Medical Clinic
    • ‘Aiea, Hawaii, United States, 96701
      • Hawaii Cancer Care - Westridge
    • ‘Aiea, Hawaii, United States, 96701
      • Pali Momi Medical Center
    • ‘Aiea, Hawaii, United States, 96701
      • Queen's Cancer Center - Pearlridge
    • ‘Aiea, Hawaii, United States, 96701
      • The Cancer Center of Hawaii-Pali Momi
  • Idaho
    • Boise, Idaho, United States, 83712
      • Saint Luke's Cancer Institute - Boise
    • Caldwell, Idaho, United States, 83605
      • Saint Alphonsus Cancer Care Center-Caldwell
    • Fruitland, Idaho, United States, 83619
      • Saint Luke's Cancer Institute - Fruitland
    • Meridian, Idaho, United States, 83642
      • Saint Luke's Cancer Institute - Meridian
    • Nampa, Idaho, United States, 83687
      • Saint Alphonsus Cancer Care Center-Nampa
    • Nampa, Idaho, United States, 83687
      • Saint Luke's Cancer Institute - Nampa
    • Twin Falls, Idaho, United States, 83301
      • Saint Luke's Cancer Institute - Twin Falls
  • Illinois
    • Bloomington, Illinois, United States, 61704
      • Illinois CancerCare-Bloomington
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare-Canton
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare-Carthage
    • Centralia, Illinois, United States, 62801
      • Centralia Oncology Clinic
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Danville, Illinois, United States, 61832
      • Carle at The Riverfront
    • DeKalb, Illinois, United States, 60115
      • Northwestern Medicine Cancer Center Kishwaukee
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Illinois - Decatur
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Effingham, Illinois, United States, 62401
      • Carle Physician Group-Effingham
    • Elmhurst, Illinois, United States, 60126
      • Elmhurst Memorial Hospital
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare-Eureka
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
    • Galesburg, Illinois, United States, 61401
      • Western Illinois Cancer Treatment Center
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Geneva, Illinois, United States, 60134
      • Northwestern Medicine Cancer Center Delnor
    • Glenview, Illinois, United States, 60026
      • NorthShore University HealthSystem-Glenbrook Hospital
    • Highland Park, Illinois, United States, 60035
      • NorthShore University HealthSystem-Highland Park Hospital
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare-Kewanee Clinic
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare-Macomb
    • Mattoon, Illinois, United States, 61938
      • Carle Physician Group-Mattoon/Charleston
    • Naperville, Illinois, United States, 60540
      • Edward Hospital/Cancer Center
    • O'Fallon, Illinois, United States, 62269
      • Cancer Care Center of O'Fallon
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Park Ridge, Illinois, United States, 60068
      • Advocate Lutheran General Hospital
    • Pekin, Illinois, United States, 61554
      • Illinois CancerCare-Pekin
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare-Peru
    • Princeton, Illinois, United States, 61356
      • Illinois CancerCare-Princeton
    • Rockford, Illinois, United States, 61114
      • UW Health Carbone Cancer Center Rockford
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University School of Medicine
    • Springfield, Illinois, United States, 62702
      • Springfield Clinic
    • Springfield, Illinois, United States, 62781
      • Springfield Memorial Hospital
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
    • Urbana, Illinois, United States, 61801
      • The Carle Foundation Hospital
    • Warrenville, Illinois, United States, 60555
      • Northwestern Medicine Cancer Center Warrenville
    • Washington, Illinois, United States, 61571
      • Illinois CancerCare - Washington
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • IU Health Methodist Hospital
  • Iowa
    • Ames, Iowa, United States, 50010
      • Mary Greeley Medical Center
    • Ames, Iowa, United States, 50010
      • McFarland Clinic - Ames
    • Clive, Iowa, United States, 50325
      • Mercy Cancer Center-West Lakes
    • Clive, Iowa, United States, 50325
      • UI Health Care Mission Cancer and Blood - West Des Moines Clinic
    • Council Bluffs, Iowa, United States, 51503
      • Heartland Oncology and Hematology LLP
    • Council Bluffs, Iowa, United States, 51503
      • Methodist Jennie Edmundson Hospital
    • Creston, Iowa, United States, 50801
      • Greater Regional Medical Center
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50314
      • Broadlawns Medical Center
    • Des Moines, Iowa, United States, 50309
      • UI Health Care Mission Cancer and Blood - Des Moines Clinic
    • Des Moines, Iowa, United States, 50314
      • UI Health Care Mission Cancer and Blood - Laurel Clinic
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
    • West Des Moines, Iowa, United States, 50266
      • Mercy Medical Center-West Lakes
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky/Markey Cancer Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center Jefferson
  • Maine
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
    • Bath, Maine, United States, 04530
      • MaineHealth Coastal Cancer Treatment Center
    • Belfast, Maine, United States, 04915
      • MaineHealth Waldo Hospital
    • Brewer, Maine, United States, 04412
      • Lafayette Family Cancer Center-EMMC
    • Portland, Maine, United States, 04102
      • MaineHealth Maine Medical Center - Portland
    • Rockport, Maine, United States, 04856
      • Penobscot Bay Medical Center
    • Sanford, Maine, United States, 04073
      • MaineHealth Cancer Care Center of York County
    • Scarborough, Maine, United States, 04074
      • Maine Medical Partners Neurology
    • Scarborough, Maine, United States, 04074
      • MaineHealth Maine Medical Center- Scarborough
    • South Portland, Maine, United States, 04106
      • MaineHealth Cancer Care and IV Therapy - South Portland
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
    • Bel Air, Maryland, United States, 21014
      • UM Upper Chesapeake Medical Center
    • Columbia, Maryland, United States, 21044
      • Central Maryland Radiation Oncology in Howard County
    • Glen Burnie, Maryland, United States, 21061
      • UM Baltimore Washington Medical Center/Tate Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
    • Brighton, Michigan, United States, 48114
      • Trinity Health IHA Medical Group Hematology Oncology - Brighton
    • Brighton, Michigan, United States, 48114
      • Trinity Health Medical Center - Brighton
    • Canton, Michigan, United States, 48188
      • Trinity Health IHA Medical Group Hematology Oncology - Canton
    • Canton, Michigan, United States, 48188
      • Trinity Health Medical Center - Canton
    • Chelsea, Michigan, United States, 48118
      • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
    • Chelsea, Michigan, United States, 48118
      • Chelsea Hospital
    • Dearborn, Michigan, United States, 48124
      • Corewell Health Dearborn Hospital
    • Detroit, Michigan, United States, 48236
      • Henry Ford Health Saint John Hospital
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grand Rapids, Michigan, United States, 49503
      • Corewell Health Grand Rapids Hospitals - Butterworth Hospital
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49048
      • Beacon Kalamazoo
    • Livonia, Michigan, United States, 48154
      • Trinity Health Saint Mary Mercy Livonia Hospital
    • Pontiac, Michigan, United States, 48341
      • Michigan Healthcare Professionals Pontiac
    • Royal Oak, Michigan, United States, 48073
      • Corewell Health William Beaumont University Hospital
    • Saginaw, Michigan, United States, 48604
      • Oncology Hematology Associates of Saginaw Valley PC
    • Saginaw, Michigan, United States, 48601
      • MyMichigan Medical Center Saginaw
    • Tawas City, Michigan, United States, 48764
      • MyMichigan Medical Center Tawas
    • Troy, Michigan, United States, 48085
      • Corewell Health Beaumont Troy Hospital
    • Warren, Michigan, United States, 48093
      • Henry Ford Health Warren Hospital
    • West Branch, Michigan, United States, 48661
      • Saint Mary's Oncology/Hematology Associates of West Branch
    • Wyoming, Michigan, United States, 49519
      • University of Michigan Health - West
    • Ypsilanti, Michigan, United States, 48197
      • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
  • Minnesota
    • Bemidji, Minnesota, United States, 56601
      • Sanford Joe Lueken Cancer Center
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Burnsville, Minnesota, United States, 55337
      • Minnesota Oncology - Burnsville
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Maple Grove, Minnesota, United States, 55369
      • Fairview Clinics and Surgery Center Maple Grove
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55454
      • Health Partners Inc
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
    • Southhaven, Mississippi, United States, 38671
      • Baptist Memorial Hospital and Cancer Center-Desoto
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Bozeman, Montana, United States, 59715
      • Bozeman Health Deaconess Hospital
    • Butte, Montana, United States, 59701
      • Saint James Community Hospital and Cancer Treatment Center
    • Great Falls, Montana, United States, 59405
      • Benefis Sletten Cancer Institute
    • Kalispell, Montana, United States, 59901
      • Logan Health Medical Center
  • Nebraska
    • Bellevue, Nebraska, United States, 68123
      • Nebraska Medicine-Bellevue
    • Lincoln, Nebraska, United States, 68516
      • Cancer Partners of Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
    • Omaha, Nebraska, United States, 68118
      • Nebraska Medicine-Village Pointe
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Livingston, New Jersey, United States, 07039
      • Saint Barnabas Medical Center
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
    • Neptune City, New Jersey, United States, 07753
      • Jersey Shore Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
    • Pennington, New Jersey, United States, 08534
      • Capital Health Medical Center-Hopewell
    • Summit, New Jersey, United States, 07902
      • Overlook Hospital
  • New York
    • New York, New York, United States, 10032
      • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
    • New York, New York, United States, 10065
      • NYP/Weill Cornell Medical Center
    • New York, New York, United States, 10016
      • Laura and Isaac Perlmutter Cancer Center at NYU Langone
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
    • West Islip, New York, United States, 11795
      • Good Samaritan University Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center/Levine Cancer Institute
    • Charlotte, North Carolina, United States, 28210
      • Atrium Health Pineville/LCI-Pineville
    • Concord, North Carolina, United States, 28025
      • Atrium Health Cabarrus/LCI-Concord
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Bismarck Medical Center
    • Fargo, North Dakota, United States, 58122
      • Sanford Roger Maris Cancer Center
    • Fargo, North Dakota, United States, 58122
      • Sanford Broadway Medical Center
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Health System - Akron Campus
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Dublin, Ohio, United States, 43016
      • Dublin Methodist Hospital
  • Oklahoma
    • Lawton, Oklahoma, United States, 73505
      • Cancer Centers of Southwest Oklahoma Research
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Clackamas, Oregon, United States, 97015
      • Clackamas Radiation Oncology Center
    • Clackamas, Oregon, United States, 97015
      • Providence Cancer Institute Clackamas Clinic
    • Gresham, Oregon, United States, 97030
      • Legacy Mount Hood Medical Center
    • Newberg, Oregon, United States, 97132
      • Providence Newberg Medical Center
    • Portland, Oregon, United States, 97210
      • Legacy Good Samaritan Hospital and Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente Northwest
    • Tualatin, Oregon, United States, 97062
      • Legacy Meridian Park Hospital
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital-Cedar Crest
    • Broomall, Pennsylvania, United States, 19008
      • Crozer-Keystone Regional Cancer Center at Broomall
    • Chadds Ford, Pennsylvania, United States, 19317
      • Christiana Care Health System-Concord Health Center
    • Lancaster, Pennsylvania, United States, 17601
      • Lancaster General Ann B Barshinger Cancer Institute
    • Lancaster, Pennsylvania, United States, 17602
      • Lancaster General Hospital
    • Monroeville, Pennsylvania, United States, 15146
      • Forbes Hospital
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute (UPCI)
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC-Shadyside Hospital
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
    • Wexford, Pennsylvania, United States, 15090
      • Wexford Health and Wellness Pavilion
  • South Carolina
    • Rock Hill, South Carolina, United States, 29730
      • Rock Hill Radiation Therapy Center
  • South Dakota
    • Pierre, South Dakota, United States, 57501
      • Avera Cancer Institute at Pierre
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
    • Sioux Falls, South Dakota, United States, 57117-5134
      • Sanford USD Medical Center - Sioux Falls
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center Oncology Clinic
  • Tennessee
    • Collierville, Tennessee, United States, 38017
      • Baptist Memorial Hospital and Cancer Center-Collierville
    • Memphis, Tennessee, United States, 38120
      • Baptist Memorial Hospital and Cancer Center-Memphis
  • Texas
    • Houston, Texas, United States, 77030
      • Memorial Hermann Texas Medical Center
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
  • Utah
    • American Fork, Utah, United States, 84003
      • American Fork Hospital / Huntsman Intermountain Cancer Center
    • Cedar City, Utah, United States, 84720
      • Sandra L Maxwell Cancer Center
    • Logan, Utah, United States, 84321
      • Logan Regional Hospital
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center
    • Riverton, Utah, United States, 84065
      • Riverton Hospital
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
    • St. George, Utah, United States, 84770
      • Saint George Regional Medical Center
  • Vermont
    • Berlin Corners, Vermont, United States, 05602
      • Central Vermont Medical Center/National Life Cancer Treatment
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
    • Burlington, Vermont, United States, 05405
      • University of Vermont and State Agricultural College
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute
    • Richmond, Virginia, United States, 23298
      • VCU Massey Comprehensive Cancer Center
    • South Hill, Virginia, United States, 23970
      • VCU Community Memorial Health Center
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Vancouver, Washington, United States, 98686
      • Legacy Salmon Creek Hospital
    • Vancouver, Washington, United States, 98684
      • Legacy Cancer Institute Medical Oncology and Day Treatment
  • West Virginia
    • Wheeling, West Virginia, United States, 26003
      • Wheeling Hospital/Schiffler Cancer Center
  • Wisconsin
    • Burlington, Wisconsin, United States, 53105
      • Aurora Cancer Care-Southern Lakes VLCC
    • Germantown, Wisconsin, United States, 53022
      • Aurora Health Care Germantown Health Center
    • Grafton, Wisconsin, United States, 53024
      • Aurora Cancer Care-Grafton
    • Green Bay, Wisconsin, United States, 54311
      • Aurora BayCare Medical Center
    • Johnson Creek, Wisconsin, United States, 53038
      • University of Wisconsin Carbone Cancer Center - Johnson Creek
    • Kenosha, Wisconsin, United States, 53142
      • Aurora Cancer Care-Kenosha South
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center - University Hospital
    • Marinette, Wisconsin, United States, 54143
      • Aurora Bay Area Medical Group-Marinette
    • Milwaukee, Wisconsin, United States, 53209
      • Aurora Cancer Care-Milwaukee
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Luke's Medical Center
    • Milwaukee, Wisconsin, United States, 53233
      • Aurora Sinai Medical Center
    • Minocqua, Wisconsin, United States, 54548
      • Marshfield Medical Center - Minocqua
    • New Richmond, Wisconsin, United States, 54017
      • Cancer Center of Western Wisconsin
    • Oshkosh, Wisconsin, United States, 54904
      • Vince Lombardi Cancer Clinic - Oshkosh
    • Racine, Wisconsin, United States, 53406
      • Aurora Cancer Care-Racine
    • Sheboygan, Wisconsin, United States, 53081
      • Vince Lombardi Cancer Clinic-Sheboygan
    • Summit, Wisconsin, United States, 53066
      • Aurora Medical Center in Summit
    • Two Rivers, Wisconsin, United States, 54241
      • Vince Lombardi Cancer Clinic-Two Rivers
    • Wauwatosa, Wisconsin, United States, 53226
      • Aurora Cancer Care-Milwaukee West
    • West Allis, Wisconsin, United States, 53227
      • Aurora West Allis Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• PRIOR TO STEP 1 REGISTRATION:
• No known IDH mutation. (If tested before step 1 registration, patients known to have IDH mutation in the tumor on local or other testing are ineligible and should not be registered)

• Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block and hematoxylin & eosin (H&E) stained slide to be sent for central pathology review for confirmation of histology and MGMT promoter methylation status. Note that tissue for central pathology review and central MGMT assessment must be received by the New York University (NYU) Center for Biospecimen Research and Development (CBRD) on or before postoperative calendar day 23. If tissue cannot be received by postoperative calendar day 23, then patients may NOT enroll on this trial as central pathology review will not be complete in time for the patient to start treatment no later than 6 weeks following surgery. Results of central pathology review and central MGMT analysis will generally be conveyed to NRG Oncology within 10 business days of receipt of tissue. Note: In the event of an additional tumor resection(s), tissue must be received within 23 days of the most recent resection and the latest resection must have been performed within 30 days after the initial resection. Surgical resection (partial or complete) is required; a limited biopsy is not allowed because it will not provide sufficient tissue for MGMT analysis

  • Note: The central pathology review and central MGMT results determine eligibility. Therefore, patients may be offered the opportunity to consent REGARDLESS of local pathology and MGMT results, and consent can occur BEFORE local pathology interpretation is finalized and BEFORE local MGMT testing is conducted

• Contrast-enhanced brain MRI within 3 days after surgery

  • MRI with Axial T2 weighted FLAIR {preferred} or T2 turbo spin echo (TSE)/fast spin echo (FSE) and 3-dimensional (3D) contrast-enhanced T1 sequences are required
  • 3D pre contrast-enhanced T1 sequences are strongly suggested
• Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP must be willing to use an adequate method of contraception hormonal or barrier method of birth control; or abstinence during and after treatment
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
• PRIOR TO STEP 2 REGISTRATION:

• Histopathologically proven diagnosis of glioblastoma (or gliosarcoma as a subtype of glioblastoma) confirmed by central pathology review

  • Note: diagnoses of "Molecular glioblastoma" per the Consortium to Inform Molecular and Practical Approaches to Central Nervous System (CNS) Tumor Taxonomy (c-IMPACT-NOW) criteria or "CNS grade 4" per the World Health Organization (WHO) 2021 criteria are NOT relevant

• MGMT promoter without methylation confirmed by central pathology review. Note: Patients with tissue that is insufficient or inadequate for analysis, fails MGMT testing, or has indeterminate or methylated MGMT promoter are excluded.

  • Note: central pathology review and central MGMT results determine eligibility; local pathology or MGMT results cannot be used for eligibility/randomization
  • Note: patients with methylated MGMT may be considered for enrollment on NRG-BN011

• IDH mutation testing by at least one method (such as immunohistochemistry for IDH1 R132H) must be performed as part of standard of care and no mutation must be found (i.e IDH wildtype). (If a mutation is identified then the patient will be ineligible and must be registered as ineligible at step 2.)

  • Note: this test is not being performed in real time as part of central review and will not be provided to sites from a centrally performed test
• History/physical examination within 28 days prior to step 2 registration
• Karnofsky Performance Status (KPS) >= 70 within 28 days prior to step 2 registration
• Neurologic function assessment within 28 days prior to step 2 registration
• Age >= 18 years
• Hemoglobin >= 10 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 10.0 g/dl is acceptable) (within 7 days prior to step 2 registration)
• Leukocytes >= 2,000/mm^3 (within 7 days prior to step 2 registration)
• Absolute neutrophil count >= 1,500/mm^3 (within 7 days prior to step 2 registration)
• Platelets >= 100,000/mm^3 (within 7 days prior to step 2 registration)
• Total bilirubin =< 1.5 x institutional/lab upper limit of normal (ULN) (within 7 days prior to step 2 registration)
• Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 2.5 x ULN (within 7 days prior to step 2 registration)
• Alanine transferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (within 7 days prior to step 2 registration)
• Serum creatinine =< 1.5 x ULN OR creatinine clearance (CrCl) >= 50 mL/min (if using the Cockcroft-Gault formula) (within 7 days prior to step 2 registration)
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

• For women of childbearing potential (WOCBP), negative serum or urine pregnancy test within 7 days prior to step 2 registration. Note that it may need to be repeated if not also within 3 days prior to treatment start

  • Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes

Exclusion Criteria:

• Prior therapy for tumor except for resection. For example, prior chemotherapy, immunotherapy, or targeted therapy for GBM or lower grade glioma is disallowed (including but not limited to temozolomide, lomustine, bevacizumab, any viral therapy, ipilimumab or other CTLA-4 antibody, PD-1 antibody, CD-137 agonist, CD40 antibody, PDL-1 or 2 antibody, vaccine therapy, polio or similar viral injection as treatment for the tumor, and/or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) as is prior Laser interstitial thermal therapy (LITT), Gliadel wafer, radiotherapy, radiosurgery, gamma knife, cyber knife, vaccine or other immunotherapy, brachytherapy, or convection enhanced delivery;

  • Note that 5-aminolevulinic acid (ALA)-mediated fluorescent guided resection (FGR) photodynamic therapy (PDT) or fluorescein administered prior to/during surgery to aid resection is not exclusionary and is not considered a chemotherapy or intracerebral agent
• Current or planned treatment with any other investigational agents for the study cancer
• Definitive clinical or radiologic evidence of metastatic disease outside the brain
• Prior invasive malignancy (except non-melanomatous skin cancer, cervical cancer in situ and melanoma in situ) unless disease free for a minimum of 2 years
• Prior radiotherapy to the head or neck that would result in overlap of radiation therapy fields
• Pregnancy and nursing females due to the potential teratogenic effects and potential risk for adverse events in nursing infants
• History of severe hypersensitivity reaction to any monoclonal antibody
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ipilimumab, nivolumab, or temozolomide
• On any dose of any systemically administered (oral, rectal, intravenous) corticosteroid within 3 days prior to step 2 registration. Inhaled, topical, and ocular corticosteroids are allowed without limitation but must be recorded. Note that treatment with systemically administered corticosteroid after initiating study treatment is allowed as needed
• Patients with known immune impairment who may be unable to respond to anti-CTLA 4 antibody
• History of interstitial lung disease including but not limited to sarcoidosis or pneumonitis
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, defined as New York Heart Association functional classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)

• Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, are excluded, as are patients on active immunosuppressive therapy. These include but are not limited to: patients with a history of immune-related neurologic disease, CNS or motor neuropathy, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as autoimmune vasculitis [e.g., Wegener's Granulomatosis]), systemic lupus erythematosus (SLE), connective tissue diseases (e.g., systemic progressive sclerosis), scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome, Hashimoto's thyroiditis, autoimmune hepatitis are excluded because of the risk of recurrence or exacerbation of disease

  • Exceptions: patients with a history of the following conditions are not excluded, unless receiving active immunosuppressive therapy:

    • Vitiligo
    • Type I diabetes
    • Rheumatoid arthritis and other arthropathies

    • Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA)

      • Anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
• Patients who have evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation are also excluded
• Current or planned therapy with warfarin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (radiation therapy, temozolomide); Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks and simultaneously receive temozolomide PO daily for 6 weeks. After radiation, patients may wear the Optune device at the discretion of the patient and their treating physician. Beginning 1 month after radiation therapy, patients receive temozolomide on days 1-5. Treatment repeats every 28 days for up to 12 cycles at the discretion of the treating investigator in the absence of disease progression or unacceptable toxicity. Patients also undergo contrast-enhanced brain MRI throughout the trial.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Energy Type; Drug: Temozolomide; Given PO; Other Names: Temodar; SCH 52365; Temodal; Temcad; Methazolastone; RP-46161; Temomedac; TMZ; CCRG-81045; Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-; M & B 39831; M and B 39831; Gliotem; Temizole; Device: NovoTTF-100A Device; Wear Optune device; Other Names: Optune; NovoTTF-100A; NovoTTF-100A System; NovoTTFields; NovoTumor Treatment Fields; Optune Device; NovoTTF-100A system (Optune); Procedure: Contrast-enhanced Magnetic Resonance Imaging; Undergo contrast-enhanced brain MRI; Other Names: CONTRAST ENHANCED MRI; Contrast-enhanced MRI; MRI With Contrast
Experimental: Arm II (radiation therapy, ipilimumab, nivolumab); Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks. Starting on the first day of radiation, patients also receive ipilimumab IV over 90 minutes Q4W for 4 doses and nivolumab IV over 30 minutes every 2 weeks until disease progression. Patients also undergo contrast-enhanced brain MRI throughout the trial.	Biological: Nivolumab; Given IV; Other Names: BMS-936558; MDX-1106; NIVO; ONO-4538; Opdivo; CMAB819; Nivolumab Biosimilar CMAB819; MDX 1106; MDX1106; BMS 936558; ABP 206; Nivolumab Biosimilar ABP 206; BCD-263; Nivolumab Biosimilar BCD-263; BMS936558; ONO 4538; ONO4538; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Biological: Ipilimumab; Given IV; Other Names: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody; BMS-734016; Ipilimumab Biosimilar CS1002; MDX-010; MDX-CTLA4; Yervoy; MDX010; BMS734016; BMS 734016; MDX 010; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Energy Type; Procedure: Contrast-enhanced Magnetic Resonance Imaging; Undergo contrast-enhanced brain MRI; Other Names: CONTRAST ENHANCED MRI; Contrast-enhanced MRI; MRI With Contrast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) (Phase II)	Disease progression was confirmed by central review and defined using an adaptation of the Response Assessment in Neuro-Oncology criteria (Wen et al, J Clin Oncol. 2010 Apr 10;28(11):1963-72. doi: 10.1200/JCO.2009.26.3541. Epub 2010 Mar 15) with modification such that the first MRI performed following completion of radiotherapy is the baseline MRI for determination of radiographic disease. Progression-free survival time is defined as time from randomization to the date of first progression, death, or the last progression assessment with no documented progression (censored). Progression-free survival rates were estimated using the Kaplan-Meier method.	From randomization to date of progression, death, or last known follow-up, whichever occurs first. Maximum follow-up time was 19.3 months.
Overall Survival (OS) (Phase III)	Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates were to be estimated by the Kaplan-Meier method.	From randomization to date of death or last known follow-up. Maximum follow-up time was 19.3 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS for the Entire Cohort (Phase II/III)	Disease progression was confirmed by central review and defined using an adaptation of the Response Assessment in Neuro-Oncology criteria (Wen et al, J Clin Oncol. 2010 Apr 10;28(11):1963-72. doi: 10.1200/JCO.2009.26.3541. Epub 2010 Mar 15) with modification such that the first MRI performed following completion of radiotherapy is the baseline MRI for determination of radiographic disease. Progression-free survival time is defined as time from randomization to the date of first progression, death, or the last progression assessment with no documented progression (censored). Progression-free survival rates were estimated using the Kaplan-Meier method.	From randomization to date of progression, death, or last known follow-up. Maximum follow-up time was 19.3 months.
Overall Survival at 2 Years	Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Two-year survival rates were to be estimated by the Kaplan-Meier method.	From randomization to two years
Number of Participants by Highest Grade Adverse Event Reported	Common Terminology Criteria for Adverse Events (version 5.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.	From randomization to date of last known follow-up. Maximum follow-up time was 19.3 months.
Change in MD Anderson Symptom Inventory for Brain Tumor (MDASI-BT) at Six Months (Patient Reported Outcomes)	The MD Anderson Symptom Inventory for brain tumor (MDASI-BT) is a 28-item multi-symptom patient-reported outcome measure assessing the severity of symptoms experienced by cancer patients and the interference with daily living caused by these symptoms, with 9 items specific to brain tumors. Each item ranges from 0 (best condition) to 10 (worst condition). A subscale score is the average of the subscale items, given that a specified minimum numbers of items were completed.	Up to 2 years
Neurocognitive Function (NCF)		Up to 2 years
Selected Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Items	Questions refer to the participants' experiences for the past 7 days of a given symptom in terms of frequency (never, rarely, occasionally, frequently, almost constantly), severity (none, mild, moderate, severe, very severe), interference with usual or daily activities (not at all, a little bit, somewhat, quite a bit, very much).	Up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS (if the Study Discontinues in Phase II)		At the end of phase II of study
Tumor Biomarker Analyses	Will assess PD-L1 expression and mutational burden expression specifically.	Up to 4 years
MGMT Protein Expression	Will assess the prognostic value of MGMT protein expression (in terms of predicting clinical outcomes such as PFS, OS, and 2-year OS rate) in the two treatment arms, separately. In addition, will evaluate if MGMT protein expression may be predictive of differential treatment effects between the two treatment arms. Correlation methods and survival modeling will be used to address these questions.	Up to 4 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: NRG Oncology
• Investigators: Principal Investigator: Andrew B Lassman, NRG Oncology

Publications and helpful links

General Publications

• 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.
• Lassman AB, Polley MC, Iwamoto FM, Sloan AE, Wang TJC, Aldape KD, Wefel JS, Gondi V, Gutierrez AN, Manasawala MH, Gilbert MR, Sulman EP, Wolchok JD, Green RM, Neil EC, Lukas RV, Goldlust SA, Snuderl M, Galbraith K, Dignam JJ, Won M, Mehta MP. Dual Immune Check Point Blockade in MGMT-Unmethylated Newly Diagnosed Glioblastoma: NRG Oncology BN007, a Randomized Phase II/III Clinical Trial. J Clin Oncol. 2025 Sep 20;43(27):3032-3040. doi: 10.1200/JCO-25-00618. Epub 2025 Aug 8.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Actual): January 13, 2023
• Study Completion (Actual): December 23, 2025

Study Registration Dates

• First Submitted: May 20, 2020
• First Submitted That Met QC Criteria: May 20, 2020
• First Posted (Actual): May 21, 2020

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Gliosarcoma; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Investigative Techniques; Therapeutics; Azoles; Pharmacologic Actions; Chemical Actions and Uses; Biological Factors; Physical Phenomena; Dacarbazine; Triazenes; Imidazoles; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Specialty Uses of Chemicals; Chemistry Techniques, Analytical; Spectrum Analysis; Receptors, Cell Surface; Membrane Proteins; Antigens; Antigens, Surface; Biomarkers; Diagnostic Uses of Chemicals; Receptors, Immunologic; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Temozolomide; Nivolumab; Ipilimumab; Radiotherapy; Radiation; Magnetic Resonance Spectroscopy; Contrast Media; CTLA-4 Antigen
• Other Study ID Numbers: NCI-2020-03404 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180868 (U.S. NIH Grant/Contract); NRG-BN007 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No