A Study Testing the Effect of Immunotherapy (Ipilimumab and Nivolumab) in Patients With Recurrent Glioma With Elevated Mutational Burden
Astrocytoma, IDH-Mutant, Grade 4, Diffuse Glioma, Glioblastoma, IDH-Wildtype
About this trial
This is an interventional treatment trial for Astrocytoma, IDH-Mutant, Grade 4
Eligibility Criteria
Inclusion Criteria:
- PRE-REGISTRATION ELIGIBILITY CRITERIA:
Histologically confirmed glioblastoma (World Health Organization [WHO] grade IV) presenting at first or second recurrence including secondary glioblastoma
Glioblastoma IDH-wildtype central nervous system (CNS) WHO grade 4
- Diffuse, astrocytic glioma IDH-wildtype with one or more of the following histological or genetic features: microvascular proliferation, necrosis, TERT promoter mutation, EGFR gene amplification, +7/-10 chromosome copy-number changes
Astrocytoma, IDH-mutant CNS WHO grade 4
- Diffuse astrocytic glioma IDH-mutant (with frequent ATRX and/or TP53 mutation and absence of 1p/19q codeletion), with necrosis and/or microvascular proliferation or one with lower grade histological features displaying homozygous deletion of CDKN2A and/or CDKN2B
- NOTE: The eligibility criteria were changed to include the new diagnostic language from the WHO 2021 pathology classification change. The above diagnoses therefore reflect the change and include the entities that were previously eligible but now carry updated pathologic classification
- Presence of measurable disease, as defined by a bidimensionally measurable lesion on magnetic resonance imaging (MRI) with a minimum diameter of 10 mm in both dimensions, prior to resection or biopsy of recurrent tumor
- Tissue available from surgical resection or biopsy of recurrent tumor =< 28 days prior to pre-registration, or planned surgery or biopsy of recurrent tumor =< 28 days after pre-registration
- Does not require > 4 mg dexamethasone beyond the perioperative period defined as the time =< 2 weeks after surgical procedure
No active autoimmune disease or history of autoimmune disease
- These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, 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 should be excluded because of the risk of recurrence or exacerbation of disease
- Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with 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
- No prior treatment with checkpoint blockade therapies (anti-CTLA4, anti-PD1/PD-L1) or bevacizumab
- No prior treatment with laser ablation at the time of recurrent tumor tissue sampling. Patients who have previously undergone laser ablation >= 4 months prior to recurrent tumor tissue sampling can be included
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Able to undergo brain MRI with contrast
- Absolute neutrophil count >= 1500/mm^3
- Platelet count >= 100,000/mm^3
Total bilirubin =< 1.5 x upper limit of normal (ULN)
- If Gilbert syndrome, then total bilirubin =< 3 x ULN
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.0 x ULN
- Creatinine =< 1.5 x ULN OR creatinine clearance (CrCl) >= 50 mL/min (if using the Cockcroft-Gault formula)
- History of active malignancy (outside of the patient's glioblastoma) that has required treatment within the previous 2 years. Participant with prior history of in situ cancer or basal or squamous cell skin cancer are eligible
- REGISTRATION ELIGIBILITY CRITERIA: Tissue obtained from biopsy or resection at first or second recurrence exhibits TMB >= 10 on FoundationOne CDx testing
Sites / Locations
- Anchorage Associates in Radiation Medicine
- Anchorage Radiation Therapy Center
- Alaska Breast Care and Surgery LLC
- Alaska Oncology and Hematology LLC
- Alaska Women's Cancer Care
- Anchorage Oncology Centre
- Katmai Oncology Group
- Providence Alaska Medical Center
- Cancer Center at Saint Joseph's
- Mayo Clinic Hospital in Arizona
- Mayo Clinic in Arizona
- Mercy Hospital Fort Smith
- CHI Saint Vincent Cancer Center Hot Springs
- Mission Hope Medical Oncology - Arroyo Grande
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
- UC San Diego Moores Cancer CenterRecruiting
- Cedars Sinai Medical CenterRecruiting
- University of California Davis Comprehensive Cancer CenterRecruiting
- Pacific Central Coast Health Center-San Luis Obispo
- Mission Hope Medical Oncology - Santa Maria
- Torrance Memorial Physician Network - Cancer Care
- Torrance Memorial Medical Center
- UCHealth University of Colorado HospitalRecruiting
- Rocky Mountain Cancer Centers-BoulderRecruiting
- Penrose-Saint Francis HealthcareRecruiting
- Rocky Mountain Cancer Centers-Penrose
- Porter Adventist HospitalRecruiting
- Mercy Medical Center
- Southwest Oncology PC
- Saint Anthony Hospital
- Littleton Adventist HospitalRecruiting
- Longmont United Hospital
- Rocky Mountain Cancer Centers-Longmont
- Parker Adventist HospitalRecruiting
- Saint Mary Corwin Medical Center
- Beebe South Coastal Health CampusRecruiting
- Beebe Medical Center
- Delaware Clinical and Laboratory Physicians PA
- Helen F Graham Cancer CenterRecruiting
- Medical Oncology Hematology Consultants PARecruiting
- Christiana Care Health System-Christiana Hospital
- Beebe Health CampusRecruiting
- TidalHealth Nanticoke / Allen Cancer Center
- Christiana Care Health System-Wilmington Hospital
- Holy Cross Hospital
- Mayo Clinic in Florida
- Emory University Hospital/Winship Cancer InstituteRecruiting
- Low Country Cancer Care
- Memorial Health University Medical CenterRecruiting
- Saint Alphonsus Cancer Care Center-BoiseRecruiting
- Saint Luke's Cancer Institute - BoiseRecruiting
- Saint Alphonsus Cancer Care Center-CaldwellRecruiting
- Kootenai Health - Coeur d'AleneRecruiting
- Walter Knox Memorial Hospital
- Saint Luke's Cancer Institute - FruitlandRecruiting
- Idaho Urologic Institute-Meridian
- Saint Luke's Cancer Institute - MeridianRecruiting
- Saint Luke's Cancer Institute - NampaRecruiting
- Saint Alphonsus Cancer Care Center-NampaRecruiting
- Kootenai Clinic Cancer Services - Post FallsRecruiting
- Kootenai Cancer ClinicRecruiting
- Saint Luke's Cancer Institute - Twin FallsRecruiting
- Saint Anthony's Health
- Rush - Copley Medical CenterRecruiting
- Illinois CancerCare-Bloomington
- Illinois CancerCare-Canton
- Memorial Hospital of Carbondale
- SIH Cancer Institute
- Illinois CancerCare-Carthage
- Centralia Oncology Clinic
- Northwestern University
- University of IllinoisRecruiting
- Carle at The RiverfrontRecruiting
- Cancer Care Specialists of Illinois - DecaturRecruiting
- Decatur Memorial Hospital
- Illinois CancerCare-Dixon
- Carle Physician Group-EffinghamRecruiting
- Crossroads Cancer CenterRecruiting
- Illinois CancerCare-Eureka
- NorthShore University HealthSystem-Evanston HospitalRecruiting
- Illinois CancerCare-Galesburg
- Western Illinois Cancer Treatment Center
- NorthShore University HealthSystem-Glenbrook HospitalRecruiting
- NorthShore University HealthSystem-Highland Park HospitalRecruiting
- Illinois CancerCare-Kewanee Clinic
- Northwestern Medicine Lake Forest Hospital
- Illinois CancerCare-Macomb
- Carle Physician Group-Mattoon/CharlestonRecruiting
- Good Samaritan Regional Health Center
- Cancer Care Center of O'FallonRecruiting
- Illinois CancerCare-Ottawa Clinic
- Illinois CancerCare-Pekin
- OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
- Illinois CancerCare-PeoriaRecruiting
- OSF Saint Francis Radiation Oncology at Peoria Cancer Center
- Methodist Medical Center of Illinois
- OSF Saint Francis Medical Center
- Illinois CancerCare-Peru
- Valley Radiation Oncology
- Illinois CancerCare-Princeton
- North Shore Medical Center
- Southern Illinois University School of MedicineRecruiting
- Springfield ClinicRecruiting
- Memorial Medical CenterRecruiting
- Carle Cancer CenterRecruiting
- The Carle Foundation Hospital
- Illinois CancerCare - Washington
- Rush-Copley Healthcare Center
- Baptist Health Floyd
- Mary Greeley Medical CenterRecruiting
- McFarland Clinic - AmesRecruiting
- McFarland Clinic - BooneRecruiting
- Saint Anthony Regional Hospital
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Cancer Center-West Lakes
- Jennie Edmundson Memorial HospitalRecruiting
- Alegent Health Mercy Hospital
- Heartland Oncology and Hematology LLPRecruiting
- Greater Regional Medical Center
- Iowa Methodist Medical Center
- Medical Oncology and Hematology Associates-Des Moines
- Broadlawns Medical Center
- Mercy Medical Center - Des MoinesRecruiting
- Mission Cancer and Blood - Laurel
- Iowa Lutheran Hospital
- McFarland Clinic - Trinity Cancer CenterRecruiting
- Trinity Regional Medical Center
- McFarland Clinic - JeffersonRecruiting
- McFarland Clinic - MarshalltownRecruiting
- Methodist West Hospital
- Mercy Medical Center-West Lakes
- Cancer Center of Kansas - Chanute
- Cancer Center of Kansas - Dodge City
- Cancer Center of Kansas - El Dorado
- Central Care Cancer Center - Garden City
- Central Care Cancer Center - Great Bend
- Cancer Center of Kansas-Independence
- Cancer Center of Kansas-Kingman
- Cancer Center of Kansas-Liberal
- Cancer Center of Kansas-Manhattan
- Cancer Center of Kansas - McPherson
- Cancer Center of Kansas - Newton
- Cancer Center of Kansas - Parsons
- Cancer Center of Kansas - Pratt
- Cancer Center of Kansas - Salina
- Cancer Center of Kansas - Wellington
- Cancer Center of Kansas-Wichita Medical Arts TowerRecruiting
- Ascension Via Christi Hospitals WichitaRecruiting
- Cancer Center of Kansas - WichitaRecruiting
- Cancer Center of Kansas - Winfield
- Flaget Memorial Hospital
- Commonwealth Cancer Center-Corbin
- Baptist Health Lexington
- Saint Joseph Radiation Oncology Resource Center
- Saint Joseph Hospital East
- Saint Joseph London
- Jewish Hospital
- Baptist Health LouisvilleRecruiting
- Saints Mary and Elizabeth Hospital
- UofL Health Medical Center Northeast
- Jewish Hospital Medical Center South
- Ochsner LSU Health Monroe Medical CenterRecruiting
- LSU Health Sciences Center at ShreveportRecruiting
- Saint Joseph Mercy HospitalRecruiting
- Bronson Battle CreekRecruiting
- Saint Joseph Mercy BrightonRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - BrightonRecruiting
- Saint Joseph Mercy CantonRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - CantonRecruiting
- Caro Cancer Center
- Saint Joseph Mercy ChelseaRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea HospitalRecruiting
- Hematology Oncology Consultants-Clarkston
- Newland Medical Associates-Clarkston
- Ascension Saint John Hospital
- Great Lakes Cancer Management Specialists-Doctors Park
- Genesee Cancer and Blood Disease Treatment CenterRecruiting
- Genesee Hematology Oncology PCRecruiting
- Genesys Hurley Cancer InstituteRecruiting
- Hurley Medical CenterRecruiting
- Helen DeVos Children's Hospital at Spectrum Health
- Spectrum Health at Butterworth CampusRecruiting
- Trinity Health Grand Rapids HospitalRecruiting
- Academic Hematology Oncology Specialists
- Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
- Michigan Breast Specialists-Grosse Pointe Woods
- Bronson Methodist HospitalRecruiting
- West Michigan Cancer CenterRecruiting
- Ascension Borgess Cancer CenterRecruiting
- Borgess Medical Center
- Sparrow Hospital
- Hope Cancer Clinic
- Trinity Health Saint Mary Mercy Livonia HospitalRecruiting
- Great Lakes Cancer Management Specialists-Macomb Medical Campus
- Michigan Breast Specialists-Macomb Township
- Saint Mary's Oncology/Hematology Associates of Marlette
- Trinity Health Muskegon HospitalRecruiting
- Lakeland Hospital Niles
- Cancer and Hematology Centers of Western Michigan - Norton ShoresRecruiting
- 21st Century Oncology-Pontiac
- Hope Cancer Center
- Newland Medical Associates-Pontiac
- Saint Joseph Mercy Oakland
- Spectrum Health Reed City HospitalRecruiting
- Great Lakes Cancer Management Specialists-Rochester Hills
- William Beaumont Hospital-Royal OakRecruiting
- Ascension Saint Mary's HospitalRecruiting
- Oncology Hematology Associates of Saginaw Valley PCRecruiting
- Lakeland Medical Center Saint Joseph
- Marie Yeager Cancer CenterRecruiting
- Bhadresh Nayak MD PC-Sterling Heights
- Ascension Saint Joseph HospitalRecruiting
- Munson Medical CenterRecruiting
- William Beaumont Hospital - TroyRecruiting
- Advanced Breast Care Center PLLC
- Great Lakes Cancer Management Specialists-Macomb Professional Building
- Macomb Hematology Oncology PC
- Michigan Breast Specialists-Warren
- Saint John Macomb-Oakland Hospital
- Saint Mary's Oncology/Hematology Associates of West BranchRecruiting
- University of Michigan Health - WestRecruiting
- Huron Gastroenterology PCRecruiting
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor CampusRecruiting
- Sanford Joe Lueken Cancer CenterRecruiting
- Essentia Health Saint Joseph's Medical CenterRecruiting
- Fairview Ridges Hospital
- Minnesota Oncology - Burnsville
- Cambridge Medical Center
- Mercy Hospital
- Essentia Health - Deer River ClinicRecruiting
- Essentia Health Cancer CenterRecruiting
- Fairview Southdale Hospital
- Unity Hospital
- Essentia Health Hibbing ClinicRecruiting
- Fairview Clinics and Surgery Center Maple Grove
- Minnesota Oncology Hematology PA-Maplewood
- Saint John's Hospital - HealtheastRecruiting
- Abbott-Northwestern HospitalRecruiting
- Hennepin County Medical CenterRecruiting
- Health Partners Inc
- Monticello Cancer Center
- New Ulm Medical Center
- Fairview Northland Medical Center
- North Memorial Medical Health Center
- Mayo Clinic in Rochester
- Coborn Cancer Center at Saint Cloud HospitalRecruiting
- Park Nicollet Clinic - Saint Louis ParkRecruiting
- Regions HospitalRecruiting
- United Hospital
- Essentia Health SandstoneRecruiting
- Saint Francis Regional Medical Center
- Lakeview Hospital
- Sanford Thief River Falls Medical Center
- Essentia Health Virginia ClinicRecruiting
- Ridgeview Medical Center
- Rice Memorial Hospital
- Minnesota Oncology Hematology PA-Woodbury
- Sanford Cancer Center Worthington
- Fairview Lakes Medical Center
- Saint Louis Cancer and Breast Institute-Ballwin
- Central Care Cancer Center - Bolivar
- Saint Francis Medical Center
- Southeast Cancer Center
- Siteman Cancer Center at West County HospitalRecruiting
- Parkland Health Center - Farmington
- Capital Region Southwest Campus
- Freeman Health System
- Mercy Hospital Joplin
- Delbert Day Cancer Institute at PCRMC
- Mercy Clinic-Rolla-Cancer and Hematology
- Heartland Regional Medical Center
- Saint Louis Cancer and Breast Institute-South City
- Washington University School of MedicineRecruiting
- Mercy Hospital South
- Siteman Cancer Center-South CountyRecruiting
- Missouri Baptist Medical Center
- Mercy Hospital Saint LouisRecruiting
- Sainte Genevieve County Memorial Hospital
- Mercy Hospital Springfield
- CoxHealth South HospitalRecruiting
- Missouri Baptist Sullivan Hospital
- Missouri Baptist Outpatient Center-Sunset Hills
- Mercy Hospital Washington
- Community Hospital of AnacondaRecruiting
- Billings Clinic Cancer CenterRecruiting
- Bozeman Deaconess HospitalRecruiting
- Benefis Healthcare- Sletten Cancer InstituteRecruiting
- Great Falls Clinic
- Kalispell Regional Medical CenterRecruiting
- Saint Patrick Hospital - Community Hospital
- Community Medical HospitalRecruiting
- CHI Health Saint Francis
- CHI Health Good Samaritan
- Saint Elizabeth Regional Medical Center
- Cancer Partners of Nebraska - Pine LakeRecruiting
- Southeast Nebraska Cancer Center - 68th Street PlaceRecruiting
- Nebraska Cancer Specialists/Oncology Hematology West PC - MECCRecruiting
- Nebraska Methodist HospitalRecruiting
- Oncology Associates PCRecruiting
- Alegent Health Immanuel Medical Center
- Alegent Health Bergan Mercy Medical Center
- Alegent Health Lakeside Hospital
- Creighton University Medical Center
- Midlands Community Hospital
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer CenterRecruiting
- Morristown Medical Center
- Jersey Shore Medical CenterRecruiting
- Capital Health Medical Center-HopewellRecruiting
- Overlook HospitalRecruiting
- Roswell Park Cancer InstituteRecruiting
- Randolph Hospital
- Messino Cancer Centers
- Cone Health Cancer Center at Alamance RegionalRecruiting
- Cone Health Cancer CenterRecruiting
- Cone Health Cancer Center at Drawbridge ParkwayRecruiting
- ECU Health Medical CenterRecruiting
- Cone Heath Cancer Center at Mebane
- Sanford Bismarck Medical CenterRecruiting
- Essentia Health Cancer Center-South University ClinicRecruiting
- Sanford South University Medical Center
- Southpointe-Sanford Medical Center Fargo
- Sanford Medical Center Fargo
- Sanford Broadway Medical CenterRecruiting
- Sanford Roger Maris Cancer CenterRecruiting
- Miami Valley Hospital SouthRecruiting
- University of Cincinnati Cancer Center-UC Medical Center
- Good Samaritan Hospital - Cincinnati
- Bethesda North Hospital
- TriHealth Cancer Institute-Westside
- TriHealth Cancer Institute-Anderson
- Ohio State University Comprehensive Cancer Center
- Dayton Blood and Cancer CenterRecruiting
- Miami Valley HospitalRecruiting
- Dayton Physician LLC-Miami Valley Hospital NorthRecruiting
- Miami Valley Hospital NorthRecruiting
- Atrium Medical Center-Middletown Regional HospitalRecruiting
- Greater Dayton Cancer CenterRecruiting
- Kettering Medical CenterRecruiting
- Upper Valley Medical CenterRecruiting
- University of Cincinnati Cancer Center-West Chester
- Cancer Centers of Southwest Oklahoma ResearchRecruiting
- University of Oklahoma Health Sciences CenterRecruiting
- Mercy Hospital Oklahoma City
- Saint Alphonsus Medical Center-Baker City
- Saint Charles Health System
- Clackamas Radiation Oncology Center
- Providence Cancer Institute Clackamas ClinicRecruiting
- Bay Area Hospital
- Providence Newberg Medical CenterRecruiting
- Saint Alphonsus Medical Center-OntarioRecruiting
- Providence Portland Medical CenterRecruiting
- Providence Saint Vincent Medical CenterRecruiting
- Saint Charles Health System-Redmond
- Lehigh Valley Hospital-Cedar CrestRecruiting
- Lehigh Valley Hospital - MuhlenbergRecruiting
- Christiana Care Health System-Concord Health Center
- Pocono Medical Center
- Lehigh Valley Hospital-Hazleton
- University of Pittsburgh Cancer Institute (UPCI)Recruiting
- Reading HospitalRecruiting
- Gibbs Cancer Center-PelhamRecruiting
- Spartanburg Medical CenterRecruiting
- Sanford Cancer Center Oncology ClinicRecruiting
- Sanford USD Medical Center - Sioux FallsRecruiting
- Saint Joseph Regional Cancer Center
- Parkland Memorial Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- Huntsman Cancer Institute/University of Utah
- Inova Schar Cancer InstituteRecruiting
- Inova Fairfax HospitalRecruiting
- Providence Regional Cancer System-Aberdeen
- PeaceHealth Saint Joseph Medical Center
- Harrison HealthPartners Hematology and Oncology-BremertonRecruiting
- Harrison Medical Center
- Highline Medical Center-Main Campus
- Providence Regional Cancer System-Centralia
- Swedish Cancer Institute-Edmonds
- Saint Elizabeth Hospital
- Providence Regional Cancer Partnership
- Saint Francis Hospital
- Swedish Cancer Institute-Issaquah
- Kadlec Clinic Hematology and OncologyRecruiting
- Providence Regional Cancer System-Lacey
- Saint Clare Hospital
- PeaceHealth Saint John Medical Center
- Jefferson HealthcareRecruiting
- Harrison HealthPartners Hematology and Oncology-Poulsbo
- Pacific Gynecology Specialists
- Swedish Medical Center-Ballard Campus
- Swedish Medical Center-Cherry Hill
- Swedish Medical Center-First Hill
- PeaceHealth United General Medical Center
- Providence Regional Cancer System-Shelton
- Franciscan Research Center-Northwest Medical Plaza
- Northwest Medical Specialties PLLC
- PeaceHealth Southwest Medical Center
- Providence Saint Mary Regional Cancer Center
- Providence Regional Cancer System-Yelm
- United Hospital Center
- WVUH-Berkely Medical Center
- West Virginia University HealthcareRecruiting
- Camden Clark Medical Center
- Duluth Clinic AshlandRecruiting
- Mayo Clinic Health System-Eau Claire Clinic
- Gundersen Lutheran Medical CenterRecruiting
- Mayo Clinic Health System-Franciscan Healthcare
- ProHealth D N Greenwald CenterRecruiting
- Cancer Center of Western Wisconsin
- ProHealth Oconomowoc Memorial HospitalRecruiting
- ProHealth Waukesha Memorial HospitalRecruiting
- UW Cancer Center at ProHealth CareRecruiting
- Billings Clinic-Cody
- Welch Cancer Center
- Pan American Center for Oncology Trials LLC
Arms of the Study
Arm 1
Experimental
Treatment (nivolumab, ipilimumab)
Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI throughout the study.