Testing Addition of an Anti-cancer Drug, Vorasidenib to Temozolomide, After Radiation for Advanced Brain Cancer
Start Date
6/24/2026
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
AIS Cancer Center at San Joaquin Community Hospital
Bakersfield, California 93301
United States
City of Hope Comprehensive Cancer Center
Duarte, California 91010
United States
Kaiser Permanente Dublin
Dublin, California 94568
United States
Kaiser Permanente-Fremont
Fremont, California 94538
United States
Kaiser Permanente Fresno Orchard Plaza
Fresno, California 93720
United States
Kaiser Permanente-Fresno
Fresno, California 93720
United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California 92612
United States
Kaiser Permanente- Modesto MOB II
Modesto, California 95356
United States
Kaiser Permanente-Oakland
Oakland, California 94611
United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California 92868
United States
Kaiser Permanente-Roseville
Roseville, California 95661
United States
Kaiser Permanente Downtown Commons
Sacramento, California 95814
United States
University of California Davis Comprehensive Cancer Center
Sacramento, California 95817
United States
Kaiser Permanente-South Sacramento
Sacramento, California 95823
United States
Kaiser Permanente-San Francisco
San Francisco, California 94115
United States
Kaiser Permanente-Santa Teresa-San Jose
San Jose, California 95119
United States
Kaiser Permanente San Leandro
San Leandro, California 94577
United States
Kaiser San Rafael-Gallinas
San Rafael, California 94903
United States
Kaiser Permanente Medical Center - Santa Clara
Santa Clara, California 95051
United States
Kaiser Permanente-Santa Rosa
Santa Rosa, California 95403
United States
Kaiser Permanente-South San Francisco
South San Francisco, California 94080
United States
Kaiser Permanente-Vallejo
Vallejo, California 94589
United States
Kaiser Permanente-Walnut Creek
Walnut Creek, California 94596
United States
John Muir Medical Center-Walnut Creek
Walnut Creek, California 94598
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
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida 33146
United States
UM Sylvester Comprehensive Cancer Center at Coral Springs
Coral Springs, Florida 33065
United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida 33442
United States
UM Sylvester Comprehensive Cancer Center at Doral
Doral, Florida 33166
United States
UM Sylvester Comprehensive Cancer Center at Hollywood
Hollywood, Florida 33021
United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida 33136
United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida 33176
United States
University of Miami Sylvester Comprehensive Cancer Center at Sole Mia
North Miami, Florida 33181
United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida 33324
United States
Augusta University Medical Center
Augusta, Georgia 30912
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
University of Kansas Cancer Center
Kansas City, Kansas 66160
United States
Lawrence Memorial Hospital
Lawrence, Kansas 66044
United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas 66210
United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas 66211
United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas 66205
United States
The James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky 40202
United States
UofL Health Medical Center Northeast
Louisville, Kentucky 40245
United States
West Jefferson Medical Center
Marrero, Louisiana 70072
United States
East Jefferson General Hospital
Metairie, Louisiana 70006
United States
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
Tufts Medical Center
Boston, Massachusetts 02111
United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts 02114
United States
Dana-Farber Cancer Institute
Boston, Massachusetts 02215
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
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan 49503
United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan 49503
United States
Trinity Health Grand Rapids Hospital
Grand Rapids, Michigan 49503
United States
University of Michigan Health - West
Wyoming, Michigan 49519
United States
Mercy Hospital
Coon Rapids, Minnesota 55433
United States
Fairview Southdale Hospital
Edina, Minnesota 55435
United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota 55407
United States
Coborn Cancer Center at Saint Cloud Hospital
Saint Cloud, Minnesota 56303
United States
Regions Hospital
Saint Paul, Minnesota 55101
United States
United Hospital
Saint Paul, Minnesota 55102
United States
University of Mississippi Medical Center
Jackson, Mississippi 39216
United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri 63376
United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri 63141
United States
University of Kansas Cancer Center - Briarcliff
Kansas City, Missouri 64116
United States
University of Kansas Cancer Center - North
Kansas City, Missouri 64154
United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri 64064
United States
Mercy Hospital Springfield
Springfield, Missouri 65804
United States
Washington University School of Medicine
St Louis, Missouri 63110
United States
Siteman Cancer Center-South County
St Louis, Missouri 63129
United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri 63136
United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey 07920
United States
Hackensack University Medical Center
Hackensack, New Jersey 07601
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
NYU Langone Hospital - Brooklyn
Brooklyn, New York 11220
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
NYU Langone Hospital - Long Island
Mineola, New York 11501
United States
Northern Westchester Hospital
Mount Kisco, New York 10549
United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York 10016
United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York 10032
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
Providence Portland Medical Center
Portland, Oregon 97213
United States
Providence Saint Vincent Medical Center
Portland, Oregon 97225
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
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania 15232
United States
UPMC-Shadyside Hospital
Pittsburgh, Pennsylvania 15232
United States
Wexford Health and Wellness Pavilion
Wexford, Pennsylvania 15090
United States
Medical University of South Carolina
Charleston, South Carolina 29425
United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah 84112
United States
University of Vermont Medical Center
Burlington, Vermont 05401
United States
University of Vermont and State Agricultural College
Burlington, Vermont 05405
United States
Swedish Medical Center-First Hill
Seattle, Washington 98122
United States
Froedtert Menomonee Falls Hospital
Menomonee Falls, Wisconsin 53051
United States
Medical College of Wisconsin
Milwaukee, Wisconsin 53226
United States
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