Testing Addition of an Anti-cancer Drug, Vorasidenib to Temozolomide, After Radiation for Advanced Brain Cancer
Phase III Trial of Radiotherapy Followed by Adjuvant Temozolomide in Combination With the IDH Inhibitor Vorasidenib vs Placebo in IDH-Mutated Newly-Diagnosed Grade 3 Astrocytomas
2 other identifiers
interventional
408
1 country
152
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jun 2026
Longer than P75 for phase_3
152 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 9, 2025
CompletedFirst Posted
Study publicly available on registry
October 14, 2025
CompletedStudy Start
First participant enrolled
June 24, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 31, 2033
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 1, 2040
October 2, 2026
October 1, 2026
6.9 years
October 9, 2025
October 1, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Progression free survival (PFS) by blinded independent central review (BICR)
This is defined as the time from randomization to the time of documented disease progression, as determined by BICR using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria or death due to any cause. PFS distributions will be evaluated for each arm and will be graphically and quantitatively compared using Kaplan-Meier methods. These methods will be used to estimate the median PFS as well as 2-, 3-, and 5-year estimates for PFS by treatment arm along with corresponding 95% confidence intervals. Cox proportional hazards models will also be used to assess influential factors on PFS both in the univariate and the multivariable settings.
assessed up to 10 years
Secondary Outcomes (16)
Progression free survival (PFS) by local review
up to 10 years
Incidence of adverse events (AEs)
Up to 30 days after last dose of study treatment
Overall survival (OS)
up to 10 years
Objective response rate (ORR) by blinded independent central review (BICR)
up to 10 years
Complete response (CR) + partial response (PR) rate by blinded independent central review (BICR)
up to 10 years
- +11 more secondary outcomes
Other Outcomes (4)
Health related quality of life
up to 3 years
Symptom burden
up to 3 years
Correlation of tumor genotype with PFS
up to 10 years
- +1 more other outcomes
Study Arms (2)
Arm I (temozolomide, placebo)
PLACEBO COMPARATORPatients 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 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 MRI throughout the study.
Arm II (temozolomide, vorasidenib)
EXPERIMENTALPatients 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.
Interventions
Undergo IMRT/VMAT
Undergo PBS
Undergo IMRT/VMAT
Undergo IMPT
Undergo blood sample collection
Undergo MRI
Ancillary Studies
Eligibility Criteria
You may qualify if:
- STEP 0: Histologic diagnosis of astrocytoma, IDH-mutant (central nervous system \[CNS\] WHO grade 3)
- STEP 0: Available diagnostic slides (hematoxylin and eosin staining method \[H\&E\] and immunohistochemical stains for central review)
- STEP 0: Tissue available for central biomarker testing (CDKN2A/B and1p/19q co-deletion \[all patients\], and IDH1/IDH2 \[if needed\])
- STEP 1: Centrally-confirmed diagnosis of astrocytoma, IDH-mutant (CNS WHO grade 3)
- STEP 1: Presence of IDH1 p.R132 or IDH2 p.172 mutation, confirmed by central review of immunohistochemical stain or molecular testing results, with central confirmation of equivocal results
- STEP 1: Absence of CDKN2A/B homozygous deletion by central testing
- STEP 1: Absence of whole arm 1p/19q co-deletion (i.e. intact 1p/19q) by central testing
- STEP 1: No evidence of spinal or leptomeningeal disease
- STEP 1: No prior chemotherapy, cranial irradiation, IDH-inhibitor therapy, radiotherapy, vaccine therapy, small-molecule therapy, or laser ablation
- STEP 1: Prior diagnostic surgery/resection/biopsy ≤ 6 months of registration
- STEP 1: Planned radiotherapy and adjuvant chemotherapy
- STEP 1: Age ≥ 12 years
- STEP 1: Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (or Karnofsky performance status \[KPS\] ≥ 60%)
- STEP 1: Absolute neutrophil count (ANC) ≥ 1,500/mm\^3
- STEP 1: Hemoglobin ≥ 9 g/dL
- +29 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (152)
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
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Ugonma N Chukwueke, MD
Alliance for Clinical Trials in Oncology
- STUDY CHAIR
Rifaquat M. Rahman, MD
Alliance for Clinical Trials in Oncology
- STUDY CHAIR
Patrick Y Wen, MD
Alliance for Clinical Trials in Oncology
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, CARE PROVIDER
- Masking Details
- Double-blind
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 9, 2025
First Posted
October 14, 2025
Study Start
June 24, 2026
Primary Completion (Estimated)
May 31, 2033
Study Completion (Estimated)
January 1, 2040
Last Updated
October 2, 2026
Record last verified: 2026-10