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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04396860
Other study ID # NCI-2020-03404
Secondary ID NCI-2020-03404NR
Status Active, not recruiting
Phase Phase 2/Phase 3
First received
Last updated
Start date September 1, 2020
Est. completion date March 11, 2025

Study information

Verified date March 2024
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 159
Est. completion date March 11, 2025
Est. primary completion date April 13, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

Procedure:
Contrast-enhanced Magnetic Resonance Imaging
Undergo contrast-enhanced brain MRI
Biological:
Ipilimumab
Given IV
Nivolumab
Given IV
Device:
NovoTTF-100A Device
Wear Optune device
Other:
Quality-of-Life Assessment
Ancillary studies
Questionnaire Administration
Ancillary studies
Radiation:
Radiation Therapy
Undergo radiation therapy
Drug:
Temozolomide
Given PO

Locations

Country Name City State
United States Hawaii Cancer Care - Westridge 'Aiea Hawaii
United States Pali Momi Medical Center 'Aiea Hawaii
United States Queen's Cancer Center - Pearlridge 'Aiea Hawaii
United States The Cancer Center of Hawaii-Pali Momi 'Aiea Hawaii
United States Summa Health System - Akron Campus Akron Ohio
United States Lehigh Valley Hospital-Cedar Crest Allentown Pennsylvania
United States American Fork Hospital / Huntsman Intermountain Cancer Center American Fork Utah
United States Mary Greeley Medical Center Ames Iowa
United States McFarland Clinic - Ames Ames Iowa
United States Kaiser Permanente-Anaheim Anaheim California
United States Trinity Health Saint Joseph Mercy Hospital Ann Arbor Ann Arbor Michigan
United States Sutter Auburn Faith Hospital Auburn California
United States Sutter Cancer Centers Radiation Oncology Services-Auburn Auburn California
United States Augusta University Medical Center Augusta Georgia
United States University of Maryland/Greenebaum Cancer Center Baltimore Maryland
United States Eastern Maine Medical Center Bangor Maine
United States MaineHealth Coastal Cancer Treatment Center Bath Maine
United States UM Upper Chesapeake Medical Center Bel Air Maryland
United States Waldo County General Hospital Belfast Maine
United States Nebraska Medicine-Bellevue Bellevue Nebraska
United States Sanford Joe Lueken Cancer Center Bemidji Minnesota
United States Central Vermont Medical Center/National Life Cancer Treatment Berlin Vermont
United States Billings Clinic Cancer Center Billings Montana
United States University of Alabama at Birmingham Cancer Center Birmingham Alabama
United States Sanford Bismarck Medical Center Bismarck North Dakota
United States Illinois CancerCare-Bloomington Bloomington Illinois
United States Saint Luke's Cancer Institute - Boise Boise Idaho
United States Bozeman Health Deaconess Hospital Bozeman Montana
United States Lafayette Family Cancer Center-EMMC Brewer Maine
United States Trinity Health IHA Medical Group Hematology Oncology - Brighton Brighton Michigan
United States Trinity Health Medical Center - Brighton Brighton Michigan
United States Crozer-Keystone Regional Cancer Center at Broomall Broomall Pennsylvania
United States Aurora Cancer Care-Southern Lakes VLCC Burlington Wisconsin
United States University of Vermont and State Agricultural College Burlington Vermont
United States University of Vermont Medical Center Burlington Vermont
United States Fairview Ridges Hospital Burnsville Minnesota
United States Minnesota Oncology - Burnsville Burnsville Minnesota
United States Saint James Community Hospital and Cancer Treatment Center Butte Montana
United States Saint Alphonsus Cancer Care Center-Caldwell Caldwell Idaho
United States Illinois CancerCare-Canton Canton Illinois
United States Trinity Health IHA Medical Group Hematology Oncology - Canton Canton Michigan
United States Trinity Health Medical Center - Canton Canton Michigan
United States Saint Francis Medical Center Cape Girardeau Missouri
United States Illinois CancerCare-Carthage Carthage Illinois
United States Sandra L Maxwell Cancer Center Cedar City Utah
United States Centralia Oncology Clinic Centralia Illinois
United States Christiana Care Health System-Concord Health Center Chadds Ford Pennsylvania
United States Atrium Health Pineville/LCI-Pineville Charlotte North Carolina
United States Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina
United States Saint Joseph Mercy Chelsea Chelsea Michigan
United States Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital Chelsea Michigan
United States Northwestern University Chicago Illinois
United States University of Illinois Chicago Illinois
United States Clackamas Radiation Oncology Center Clackamas Oregon
United States Providence Cancer Institute Clackamas Clinic Clackamas Oregon
United States Case Western Reserve University Cleveland Ohio
United States Cleveland Clinic Foundation Cleveland Ohio
United States Mercy Cancer Center-West Lakes Clive Iowa
United States Mission Cancer and Blood - West Des Moines Clive Iowa
United States Baptist Memorial Hospital and Cancer Center-Collierville Collierville Tennessee
United States Penrose-Saint Francis Healthcare Colorado Springs Colorado
United States Central Maryland Radiation Oncology in Howard County Columbia Maryland
United States Riverside Methodist Hospital Columbus Ohio
United States Atrium Health Cabarrus/LCI-Concord Concord North Carolina
United States John Muir Medical Center-Concord Concord California
United States Mercy Hospital Coon Rapids Minnesota
United States Heartland Oncology and Hematology LLP Council Bluffs Iowa
United States Methodist Jennie Edmundson Hospital Council Bluffs Iowa
United States Greater Regional Medical Center Creston Iowa
United States Carle at The Riverfront Danville Illinois
United States Beaumont Hospital - Dearborn Dearborn Michigan
United States Cancer Care Specialists of Illinois - Decatur Decatur Illinois
United States Decatur Memorial Hospital Decatur Illinois
United States Northwestern Medicine Cancer Center Kishwaukee DeKalb Illinois
United States Porter Adventist Hospital Denver Colorado
United States Broadlawns Medical Center Des Moines Iowa
United States Iowa Methodist Medical Center Des Moines Iowa
United States Mercy Medical Center - Des Moines Des Moines Iowa
United States Mission Cancer and Blood - Des Moines Des Moines Iowa
United States Mission Cancer and Blood - Laurel Des Moines Iowa
United States Ascension Saint John Hospital Detroit Michigan
United States Dublin Methodist Hospital Dublin Ohio
United States Fairview Southdale Hospital Edina Minnesota
United States Carle Physician Group-Effingham Effingham Illinois
United States Crossroads Cancer Center Effingham Illinois
United States Elmhurst Memorial Hospital Elmhurst Illinois
United States Illinois CancerCare-Eureka Eureka Illinois
United States NorthShore University HealthSystem-Evanston Hospital Evanston Illinois
United States Inova Schar Cancer Institute Fairfax Virginia
United States Sanford Broadway Medical Center Fargo North Dakota
United States Sanford Roger Maris Cancer Center Fargo North Dakota
United States Genesys Hurley Cancer Institute Flint Michigan
United States Hurley Medical Center Flint Michigan
United States Beebe South Coastal Health Campus Frankford Delaware
United States Unity Hospital Fridley Minnesota
United States Saint Luke's Cancer Institute - Fruitland Fruitland Idaho
United States Illinois CancerCare-Galesburg Galesburg Illinois
United States Western Illinois Cancer Treatment Center Galesburg Illinois
United States Northwestern Medicine Cancer Center Delnor Geneva Illinois
United States Aurora Health Care Germantown Health Center Germantown Wisconsin
United States UM Baltimore Washington Medical Center/Tate Cancer Center Glen Burnie Maryland
United States NorthShore University HealthSystem-Glenbrook Hospital Glenview Illinois
United States Aurora Cancer Care-Grafton Grafton Wisconsin
United States Corewell Health Grand Rapids Hospitals - Butterworth Hospital Grand Rapids Michigan
United States Benefis Sletten Cancer Institute Great Falls Montana
United States Aurora BayCare Medical Center Green Bay Wisconsin
United States Legacy Mount Hood Medical Center Gresham Oregon
United States Hackensack University Medical Center Hackensack New Jersey
United States Hartford Hospital Hartford Connecticut
United States NorthShore University HealthSystem-Highland Park Hospital Highland Park Illinois
United States Hawaii Cancer Care Inc - Waterfront Plaza Honolulu Hawaii
United States Hawaii Cancer Care Inc-Liliha Honolulu Hawaii
United States Island Urology Honolulu Hawaii
United States Kapiolani Medical Center for Women and Children Honolulu Hawaii
United States Queen's Cancer Cenrer - POB I Honolulu Hawaii
United States Queen's Cancer Center - Kuakini Honolulu Hawaii
United States Queen's Medical Center Honolulu Hawaii
United States Straub Clinic and Hospital Honolulu Hawaii
United States The Cancer Center of Hawaii-Liliha Honolulu Hawaii
United States University of Hawaii Cancer Center Honolulu Hawaii
United States Memorial Hermann Texas Medical Center Houston Texas
United States Indiana University/Melvin and Bren Simon Cancer Center Indianapolis Indiana
United States IU Health Methodist Hospital Indianapolis Indiana
United States University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa
United States University of Mississippi Medical Center Jackson Mississippi
United States Baptist MD Anderson Cancer Center Jacksonville Florida
United States University of Wisconsin Carbone Cancer Center Johnson Creek Johnson Creek Wisconsin
United States Castle Medical Center Kailua Hawaii
United States Borgess Medical Center Kalamazoo Michigan
United States Bronson Methodist Hospital Kalamazoo Michigan
United States West Michigan Cancer Center Kalamazoo Michigan
United States Kalispell Regional Medical Center Kalispell Montana
United States Aurora Cancer Care-Kenosha South Kenosha Wisconsin
United States Illinois CancerCare-Kewanee Clinic Kewanee Illinois
United States UC San Diego Moores Cancer Center La Jolla California
United States Lancaster General Ann B Barshinger Cancer Institute Lancaster Pennsylvania
United States Lancaster General Hospital Lancaster Pennsylvania
United States Cancer Centers of Southwest Oklahoma Research Lawton Oklahoma
United States Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center Lebanon New Hampshire
United States Beebe Medical Center Lewes Delaware
United States University of Kentucky/Markey Cancer Center Lexington Kentucky
United States Wilcox Memorial Hospital and Kauai Medical Clinic Lihue Hawaii
United States Cancer Partners of Nebraska Lincoln Nebraska
United States Cancer Partners of Nebraska - Pine Lake Lincoln Nebraska
United States University of Arkansas for Medical Sciences Little Rock Arkansas
United States Littleton Adventist Hospital Littleton Colorado
United States Saint Barnabas Medical Center Livingston New Jersey
United States Trinity Health Saint Mary Mercy Livonia Hospital Livonia Michigan
United States Logan Regional Hospital Logan Utah
United States Loma Linda University Medical Center Loma Linda California
United States Cedars Sinai Medical Center Los Angeles California
United States Kaiser Permanente Los Angeles Medical Center Los Angeles California
United States Illinois CancerCare-Macomb Macomb Illinois
United States University of Wisconsin Carbone Cancer Center - University Hospital Madison Wisconsin
United States Fairview Clinics and Surgery Center Maple Grove Maple Grove Minnesota
United States Minnesota Oncology Hematology PA-Maplewood Maplewood Minnesota
United States Aurora Bay Area Medical Group-Marinette Marinette Wisconsin
United States Carle Physician Group-Mattoon/Charleston Mattoon Illinois
United States Baptist Memorial Hospital and Cancer Center-Memphis Memphis Tennessee
United States Saint Luke's Cancer Institute - Meridian Meridian Idaho
United States Aurora Cancer Care-Milwaukee Milwaukee Wisconsin
United States Aurora Saint Luke's Medical Center Milwaukee Wisconsin
United States Aurora Sinai Medical Center Milwaukee Wisconsin
United States Health Partners Inc Minneapolis Minnesota
United States Hennepin County Medical Center Minneapolis Minnesota
United States Marshfield Clinic-Minocqua Center Minocqua Wisconsin
United States Forbes Hospital Monroeville Pennsylvania
United States Morristown Medical Center Morristown New Jersey
United States Intermountain Medical Center Murray Utah
United States Saint Alphonsus Cancer Care Center-Nampa Nampa Idaho
United States Saint Luke's Cancer Institute - Nampa Nampa Idaho
United States Edward Hospital/Cancer Center Naperville Illinois
United States Jersey Shore Medical Center Neptune New Jersey
United States The Hospital of Central Connecticut New Britain Connecticut
United States Rutgers Cancer Institute of New Jersey New Brunswick New Jersey
United States Ochsner Medical Center Jefferson New Orleans Louisiana
United States Tulane University School of Medicine New Orleans Louisiana
United States Cancer Center of Western Wisconsin New Richmond Wisconsin
United States Laura and Isaac Perlmutter Cancer Center at NYU Langone New York New York
United States NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center New York New York
United States NYP/Weill Cornell Medical Center New York New York
United States Christiana Care Health System-Christiana Hospital Newark Delaware
United States Delaware Clinical and Laboratory Physicians PA Newark Delaware
United States Helen F Graham Cancer Center Newark Delaware
United States Medical Oncology Hematology Consultants PA Newark Delaware
United States Providence Newberg Medical Center Newberg Oregon
United States Cancer Care Center of O'Fallon O'Fallon Illinois
United States McKay-Dee Hospital Center Ogden Utah
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Nebraska Medicine-Village Pointe Omaha Nebraska
United States Nebraska Methodist Hospital Omaha Nebraska
United States University of Nebraska Medical Center Omaha Nebraska
United States Kaiser Permanente-Ontario Ontario California
United States UC Irvine Health/Chao Family Comprehensive Cancer Center Orange California
United States AdventHealth Orlando Orlando Florida
United States Vince Lombardi Cancer Clinic - Oshkosh Oshkosh Wisconsin
United States Illinois CancerCare-Ottawa Clinic Ottawa Illinois
United States Advocate Lutheran General Hospital Park Ridge Illinois
United States Parker Adventist Hospital Parker Colorado
United States Illinois CancerCare-Pekin Pekin Illinois
United States Capital Health Medical Center-Hopewell Pennington New Jersey
United States Illinois CancerCare-Peoria Peoria Illinois
United States Methodist Medical Center of Illinois Peoria Illinois
United States OSF Saint Francis Medical Center Peoria Illinois
United States Illinois CancerCare-Peru Peru Illinois
United States Thomas Jefferson University Hospital Philadelphia Pennsylvania
United States Avera Cancer Institute at Pierre Pierre South Dakota
United States Allegheny General Hospital Pittsburgh Pennsylvania
United States University of Pittsburgh Cancer Institute (UPCI) Pittsburgh Pennsylvania
United States UPMC-Shadyside Hospital Pittsburgh Pennsylvania
United States Michigan Healthcare Professionals Pontiac Pontiac Michigan
United States Kaiser Permanente Northwest Portland Oregon
United States Legacy Good Samaritan Hospital and Medical Center Portland Oregon
United States Maine Medical Center-Bramhall Campus Portland Maine
United States Providence Portland Medical Center Portland Oregon
United States Providence Saint Vincent Medical Center Portland Oregon
United States Illinois CancerCare-Princeton Princeton Illinois
United States Utah Valley Regional Medical Center Provo Utah
United States Aurora Cancer Care-Racine Racine Wisconsin
United States Beebe Health Campus Rehoboth Beach Delaware
United States Virginia Commonwealth University/Massey Cancer Center Richmond Virginia
United States Riverton Hospital Riverton Utah
United States University of Rochester Rochester New York
United States Rock Hill Radiation Therapy Center Rock Hill South Carolina
United States UW Health Carbone Cancer Center Rockford Rockford Illinois
United States Penobscot Bay Medical Center Rockport Maine
United States Sutter Cancer Centers Radiation Oncology Services-Roseville Roseville California
United States Sutter Roseville Medical Center Roseville California
United States William Beaumont Hospital-Royal Oak Royal Oak Michigan
United States Sutter Medical Center Sacramento Sacramento California
United States University of California Davis Comprehensive Cancer Center Sacramento California
United States Ascension Saint Mary's Hospital Saginaw Michigan
United States Oncology Hematology Associates of Saginaw Valley PC Saginaw Michigan
United States Saint George Regional Medical Center Saint George Utah
United States Park Nicollet Clinic - Saint Louis Park Saint Louis Park Minnesota
United States Regions Hospital Saint Paul Minnesota
United States United Hospital Saint Paul Minnesota
United States Huntsman Cancer Institute/University of Utah Salt Lake City Utah
United States LDS Hospital Salt Lake City Utah
United States University of Texas Health Science Center at San Antonio San Antonio Texas
United States MaineHealth Cancer Care Center of York County Sanford Maine
United States Lewis Cancer and Research Pavilion at Saint Joseph's/Candler Savannah Georgia
United States Memorial Health University Medical Center Savannah Georgia
United States Maine Medical Center- Scarborough Campus Scarborough Maine
United States Maine Medical Partners Neurology Scarborough Maine
United States Virginia Mason Medical Center Seattle Washington
United States Vince Lombardi Cancer Clinic-Sheboygan Sheboygan Wisconsin
United States Avera Cancer Institute Sioux Falls South Dakota
United States Sanford Cancer Center Oncology Clinic Sioux Falls South Dakota
United States Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota
United States VCU Community Memorial Health Center South Hill Virginia
United States Maine Medical Partners - South Portland South Portland Maine
United States Baptist Memorial Hospital and Cancer Center-Desoto Southhaven Mississippi
United States Memorial Medical Center Springfield Illinois
United States Southern Illinois University School of Medicine Springfield Illinois
United States Springfield Clinic Springfield Illinois
United States Lakeview Hospital Stillwater Minnesota
United States Aurora Medical Center in Summit Summit Wisconsin
United States Overlook Hospital Summit New Jersey
United States State University of New York Upstate Medical University Syracuse New York
United States Ascension Saint Joseph Hospital Tawas City Michigan
United States Lewis Hall Singletary Oncology Center Thomasville Georgia
United States Torrance Memorial Medical Center Torrance California
United States Torrance Memorial Physician Network - Cancer Care Torrance California
United States William Beaumont Hospital - Troy Troy Michigan
United States Legacy Meridian Park Hospital Tualatin Oregon
United States Saint Luke's Cancer Institute - Twin Falls Twin Falls Idaho
United States Vince Lombardi Cancer Clinic-Two Rivers Two Rivers Wisconsin
United States Carle Cancer Center Urbana Illinois
United States The Carle Foundation Hospital Urbana Illinois
United States Legacy Cancer Institute Medical Oncology and Day Treatment Vancouver Washington
United States Legacy Salmon Creek Hospital Vancouver Washington
United States John Muir Medical Center-Walnut Creek Walnut Creek California
United States Saint John Macomb-Oakland Hospital Warren Michigan
United States Northwestern Medicine Cancer Center Warrenville Warrenville Illinois
United States Illinois CancerCare - Washington Washington Illinois
United States Aurora Cancer Care-Milwaukee West Wauwatosa Wisconsin
United States Aurora West Allis Medical Center West Allis Wisconsin
United States Saint Mary's Oncology/Hematology Associates of West Branch West Branch Michigan
United States Mercy Medical Center-West Lakes West Des Moines Iowa
United States Good Samaritan University Hospital West Islip New York
United States Reading Hospital West Reading Pennsylvania
United States Wexford Health and Wellness Pavilion Wexford Pennsylvania
United States Wheeling Hospital/Schiffler Cancer Center Wheeling West Virginia
United States University of Michigan Health - West Wyoming Michigan
United States Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus Ypsilanti Michigan

Sponsors (2)

Lead Sponsor Collaborator
National Cancer Institute (NCI) NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other OS (if the Study Discontinues in Phase II) At the end of phase II of study
Other Tumor Biomarker Analyses Will assess PD-L1 expression and mutational burden expression specifically. Up to 4 years
Other 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
Primary 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.
Primary 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 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.
Secondary 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
Secondary 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.
Secondary 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
Secondary Neurocognitive Function (NCF) Up to 2 years
Secondary 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
See also
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