Testing Addition of an Anti-cancer Drug, Vorasidenib to Temozolomide, After Radiation for Advanced Brain Cancer
Start Date
7/20/2026
Completion Date
1/1/2040
Summary
This phase III trial compares the effect of vorasidenib to placebo in combination with usual treatment, temozolomide, in treating patients with newly diagnosed grade 3 astrocytoma after radiation. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid and may kill tumor cells and slow down or stop tumor growth. Vorasidenib citrate blocks the proteins made by the mutated IDH1 and IDH2 genes, which may help keep tumor cells from growing. It is a type of enzyme inhibitor and a type of targeted therapy. Adding vorasidenib to the usual treatment, temozolomide, may be more effective than temozolomide alone in treating patients with newly diagnosed grade 3 astrocytoma after radiation therapy.
Detailed Description
The primary and secondary objectives of the study: PRIMARY OBJECTIVE: I. To determine if vorasidenib citrate (vorasidenib) and adjuvant temozolomide following radiation therapy improves progression-free survival (PFS) per blinded independent review in patients with newly-diagnosed IDH-mutant astrocytoma (World Health Organization \[WHO\] grade 3) compared to placebo given with adjuvant temozolomide following radiation therapy. SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of vorasidenib versus (vs.) placebo in combination with temozolomide, following radiation therapy. II. To evaluate PFS associated with vorasidenib vs. placebo in combination with temozolomide following radiation therapy, defined by local institutional review. III. To evaluate the efficacy of vorasidenib vs. placebo in combination with adjuvant temozolomide, following radiation therapy, based on overall survival (OS). IV. To evaluate the efficacy of vorasidenib vs. placebo in combination with temozolomide, following radiation therapy, based on objective response rate (ORR), complete response (CR) + partial response (PR), time to response, time to CR+PR, duration of response, and duration of CR+PR, with response assessed per the blinded independent review using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria in patients with measurable tumor at baseline. V. To evaluate the efficacy of vorasidenib vs. placebo in combination with temozolomide, following radiation therapy, based on ORR, CR+PR, time to response, time to CR+PR, duration of response, and duration of CR+PR, with response assessed per local institutional review or investigator using the RANO 2.0 criteria. VI. To evaluate the efficacy of vorasidenib vs. placebo in combination with temozolomide, following radiation therapy, based on time to next intervention. VII. To evaluate vorasidenib vs. placebo in combination with temozolomide, following radiation, with respect to health-related quality of life (HRQoL) as assessed by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) and symptom burden as assessed by the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT). EXPLORATORY OBJECTIVES: I. To correlate tumor genotype with PFS. II. To evaluate the effect of the addition of vorasidenib to adjuvant temozolomide on seizure control. OUTLINE: Patients are randomized 1:1 to 1 of 2 arms. ARM I (CONTROL): Patients receive intensity-modulated radiation therapy (IMRT)/volume modulated arc therapy (VMAT) or pencil beam scanning (PBS) or intensity-modulated proton therapy (IMPT) once daily (QD) on Monday-Friday for 33 fractions. Starting 4 weeks after radiotherapy, patients receive temozolomide orally (PO) QD on days 1-5 and placebo PO QD on days 1-28 of each cycle. Cycles of combination treatment repeat every 28 days for up to 12 months and placebo alone repeats every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and magnetic resonance imaging (MRI) throughout the study. ARM II (EXPERIMENTAL): Patients receive IMRT/VMAT or PBS or IMPT QD on Monday-Friday for 33 fractions. Starting 4 weeks after radiotherapy, patients receive temozolomide PO QD on days 1-5 and vorasidenib PO QD on days 1-28 of each cycle. Cycles of combination treatment repeat every 28 days for up to 12 months and vorasidenib alone repeats every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and MRI throughout the study. After completion of study treatment, patients are followed up every 3 months for the first 2 years, every 4 months for the next 2 years, and then every 6 months for up to 10 years.
Eligibility Criteria
Age Range: 12 years to No maximum
Interventions
Intensity-Modulated Radiation Therapy
Volume Modulated Arc Therapy
Pencil Beam Scanning
Intensity-Modulated Proton Therapy
Temozolomide
Vorasidenib
Placebo Administration
Biospecimen Collection
Magnetic Resonance Imaging
Questionnaire Administration
Conditions
Locations
City of Hope Comprehensive Cancer Center
Duarte, California 91010
United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California 92612
United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California 92868
United States
University of California Davis Comprehensive Cancer Center
Sacramento, California 95817
United States
Yale University
New Haven, Connecticut 06520
United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut 06611
United States
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut 06385
United States
Helen F Graham Cancer Center
Newark, Delaware 19713
United States
Medical Oncology Hematology Consultants PA
Newark, Delaware 19713
United States
OSF Saint Joseph Medical Center
Bloomington, Illinois 61701
United States
Illinois CancerCare-Bloomington
Bloomington, Illinois 61704
United States
Illinois CancerCare-Canton
Canton, Illinois 61520
United States
Illinois CancerCare-Carthage
Carthage, Illinois 62321
United States
University of Illinois
Chicago, Illinois 60612
United States
Illinois CancerCare-Eureka
Eureka, Illinois 61530
United States
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois 60201
United States
Illinois CancerCare-Galesburg
Galesburg, Illinois 61401
United States
NorthShore University HealthSystem-Glenbrook Hospital
Glenview, Illinois 60026
United States
NorthShore University HealthSystem-Highland Park Hospital
Highland Park, Illinois 60035
United States
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois 61443
United States
Illinois CancerCare-Macomb
Macomb, Illinois 61455
United States
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois 61350
United States
Illinois CancerCare-Pekin
Pekin, Illinois 61554
United States
Illinois CancerCare-Peoria
Peoria, Illinois 61615
United States
OSF Saint Francis Radiation Oncology at Peoria Cancer Center
Peoria, Illinois 61615
United States
OSF Saint Francis Medical Center
Peoria, Illinois 61637
United States
Illinois CancerCare-Peru
Peru, Illinois 61354
United States
Illinois CancerCare-Princeton
Princeton, Illinois 61356
United States
Illinois CancerCare - Washington
Washington, Illinois 61571
United States
Midwestern Regional Medical Center
Zion, Illinois 60099
United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa 50023
United States
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa 50325
United States
Iowa Methodist Medical Center
Des Moines, Iowa 50309
United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa 50309
United States
Broadlawns Medical Center
Des Moines, Iowa 50314
United States
Mercy Medical Center - Des Moines
Des Moines, Iowa 50314
United States
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa 50314
United States
UI Healthcare Mission Cancer and Blood - Pella
Pella, Iowa 50219
United States
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa 50263
United States
West Jefferson Medical Center
Marrero, Louisiana 70072
United States
East Jefferson General Hospital
Metairie, Louisiana 70006
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University Medical Center New Orleans
New Orleans, Louisiana 70112
United States
Children's Hospital New Orleans
New Orleans, Louisiana 70118
United States
MaineHealth Coastal Cancer Treatment Center
Bath, Maine 04530
United States
MaineHealth Maine Medical Center - Portland
Portland, Maine 04102
United States
MaineHealth Cancer Care Center of York County
Sanford, Maine 04073
United States
MaineHealth Maine Medical Center- Scarborough
Scarborough, Maine 04074
United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan 48109
United States
University of Michigan - Brighton Center for Specialty Care
Brighton, Michigan 48116
United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey 07920
United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey 07748
United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey 07645
United States
Northwell Health Imbert Cancer Center
Bay Shore, New York 11706
United States
Memorial Sloan Kettering Commack
Commack, New York 11725
United States
Memorial Sloan Kettering Westchester
Harrison, New York 10604
United States
Northwell Health/Center for Advanced Medicine
Lake Success, New York 11042
United States
Northern Westchester Hospital
Mount Kisco, New York 10549
United States
Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
Stony Brook University Medical Center
Stony Brook, New York 11794
United States
Memorial Sloan Kettering Nassau
Uniondale, New York 11553
United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio 45219
United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio 43210
United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio 45069
United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
United States
Christiana Care Health System-Concord Health Center
Chadds Ford, Pennsylvania 19317
United States
UPMC Hillman Cancer Center Erie
Erie, Pennsylvania 16505
United States
Forbes Hospital
Monroeville, Pennsylvania 15146
United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania 19107
United States
Allegheny General Hospital
Pittsburgh, Pennsylvania 15212
United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania 15232
United States
UPMC-Shadyside Hospital
Pittsburgh, Pennsylvania 15232
United States
Wexford Health and Wellness Pavilion
Wexford, Pennsylvania 15090
United States
University of Vermont Medical Center
Burlington, Vermont 05401
United States
University of Vermont and State Agricultural College
Burlington, Vermont 05405
United States
Froedtert Menomonee Falls Hospital
Menomonee Falls, Wisconsin 53051
United States
Medical College of Wisconsin
Milwaukee, Wisconsin 53226
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ProHealth D N Greenwald Center
Mukwonago, Wisconsin 53149
United States
Froedtert and MCW Moorland Reserve Health Center
New Berlin, Wisconsin 53151
United States
Drexel Town Square Health Center
Oak Creek, Wisconsin 53154
United States
ProHealth Oconomowoc Memorial Hospital
Oconomowoc, Wisconsin 53066
United States
UW Cancer Center at ProHealth Care
Waukesha, Wisconsin 53188
United States
Froedtert West Bend Hospital/Kraemer Cancer Center
West Bend, Wisconsin 53095
United States