New radiation rhythm may outsmart glioblastoma and save memory

NCT ID NCT07452458

Disease control Sponsor: NRG Oncology Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Sep 11, 2026 · Updated 3 times

Summary

This phase III trial tests a new way to deliver radiation called TMPRT, which gives the total dose in short pulses with breaks in between, for people with a newly diagnosed, aggressive brain cancer (MGMT-unmethylated glioblastoma). About 398 adults will be randomly assigned to get either standard radiation or TMPRT, both with the chemotherapy drug temozolomide. The goal is to see if TMPRT helps people live longer and protects memory and thinking, which often decline after standard treatment.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: Temporally-modulated pulsed radiation therapy (TMPRT) and temozolomide
What this could lead to: If it works, this could offer a new radiation approach that extends survival and better preserves memory and thinking in people with a hard-to-treat glioblastoma.
What could go wrong: This is still an early-stage trial (not yet recruiting) and previous new therapies for this tumor type have failed. The benefit over standard care is uncertain, and radiation always carries risks like fatigue and brain swelling.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 3

Large-scale testing in a bigger group. Usually the last step before a treatment can be approved.

Participants

About 398 people

The number the study aims to enrol. It can still change while the study runs.

Started

Jul 2026

Expected to finish

Jul 2035

An estimate. End dates often move.

Lead sponsor

Other sponsor

The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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 and eosin (H\&E) stained slide to be sent for central pathology review for confirmation of histology and MGMT promoter methylation status. Surgical resection is required; stereotactic biopsy alone is not allowed because it will not provide sufficient tissue for MGMT analysis. Note that tissue for central pathology review and central MGMT assessment must be shipped to the New York University (NYU) Center for Biospecimen Research and Development (CBRD) on or before postoperative calendar day 30. If tissue cannot be shipped by postoperative calendar day 30, 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 8 weeks following surgery. Results of central pathology review and central MGMT analysis will generally be completed within 10 business days of receipt of tissue. Results will be entered by the central lab directly into Rave. Note: In the event of an additional tumor resection(s), tissue must be shipped within 30 days of the most recent resection and the latest resection must have been performed within 30 days after the initial resection. * Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to Step 1 registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. * No known leptomeningeal disease or metastatic disease outside the brain. * Age ≥ 18 * Because neurocognitive testing is the primary goal of this study, patients must be proficient in English or French Canadian. * Karnofsky Performance Status ≥ 70 * Hemoglobin ≥ 10 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin (Hgb) ≥ 10.0 g/dl is acceptable) * Leukocytes ≥ 2,000/mm\^3 OR absolute neutrophil count ≥ 1,500/mm\^3 * Platelets ≥ 100,000/mm\^3 * Creatinine clearance (CrCl) ≥ 50 mL/min * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) * Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase \[SGPT\]) ≤ 3 x ULN * No prior cranial radiation therapy that would result in overlap of radiation therapy fields. * No previous therapy for GBM except surgery, laser interstitial thermal therapy (LITT) or Gliadel wafer. * Note: 5-aminolevulinic acid (ALA)-mediated fluorescence-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. * No history of unstable angina requiring hospitalization in the last 3 months * No history of myocardial infarction within the last 3 months * New York Heart Association Functional Classification II or better (NYHA Functional Classification III/IV are not eligible) (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) * No active infection currently requiring IV antibiotic management * No chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy * No movement disorder that could impede ability to lie still with an immobilization mask for approximately 40 minutes * No significant sensory deficits (i.e., blindness, mutism) that would prohibit participation of NCF testing * No history of allergic reaction attributed to compounds of similar chemical or biological composition to temozolomide * PRIOR TO STEP 2 REGISTRATION: * The following baseline neurocognitive tests must be completed within 28 days prior to Step 2 registration: (Hopkins Verbal Learning Test - Revised \[HVLT-R\], Trail Making Test \[TMT\], Controlled Oral Word Association \[COWA\]). The neurocognitive tests will be uploaded into RAVE for evaluation by Dr. Wefel. The following scores must be obtained for patient eligibility: HVLT-R Total Recall \> 5, HVLT-R Delayed Recall \> 3, HVLT-R Delayed Recognition \> -10, TMT Part A . 2738, TMT Part B . 3724, COWA . 12. Central review of the Neurocognitive tests will be completed in Rave within 3 business days after the upload is completed. Users with the Rave clinical research associate (CRA) role will be able to view the results in Rave. The CRA must confirm that the results are available and meet eligibility requirements prior to proceeding with Step 2 Registration. * NOTE: Completed baseline neurocognitive tests can be uploaded at the time of Step 1 registration. * Note: Patients whose neurocognitive test scores do not meet the criteria above will not be eligible for the study and will be reported as ineligible due to "Failure to meet Neurocognitive testing criteria" on Step 2 registration. * Pathology proven diagnosis of IDH-wildtype glioblastoma with unmethylated MGMT promoter confirmed by central pathology review. 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.) * Central pathology review will generally be completed within 10 business days of receipt of the tissue. Users with the Rave CRA role will be able to view the results in Rave. It must be confirmed that the results are available and meet eligibility requirements prior to proceeding with Step 2 Registration. * Note: Patients with tissue that is insufficient or inadequate for analysis, has failed MGMT testing, or has indeterminate or methylated MGMT promoter are excluded and will be reported as a "central pathology review failure" on step 2 registration.

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Conditions

The condition(s) this trial relates to.

glioblastoma IDH-wildtype glioblastoma

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Glioblastoma, IDH-wildtype MGMT-unmethylated glioblastoma

How to take part

Only the study team decides who joins. These are the ways to reach them.

The study's own enquiry address

This study publishes an address for enquiries. See it below .
The places running it

54 sites. The list below names each one and where it is.
The official record

ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

Open the record ↗
A doctor treating you

A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Show contact details

Locations

Alton Memorial Hospital
RECRUITING

Alton, Illinois, 62002, United States
Broadlawns Medical Center
RECRUITING

Des Moines, Iowa, 50314, United States
Cancer Care Center of O'Fallon
RECRUITING

O'Fallon, Illinois, 62269, United States
Case Western Reserve University
RECRUITING

Cleveland, Ohio, 44106, United States

Contact Email: •••••@•••••
Decatur Memorial Hospital
RECRUITING

Decatur, Illinois, 62526, United States
Drexel Town Square Health Center
RECRUITING

Oak Creek, Wisconsin, 53154, United States
Froedtert Menomonee Falls Hospital
RECRUITING

Menomonee Falls, Wisconsin, 53051, United States
Froedtert West Bend Hospital/Kraemer Cancer Center
RECRUITING

West Bend, Wisconsin, 53095, United States
Froedtert and MCW Moorland Reserve Health Center
RECRUITING

New Berlin, Wisconsin, 53151, United States
HSHS Saint Elizabeth's Hospital
RECRUITING

O'Fallon, Illinois, 62269, United States
Iowa Methodist Medical Center
RECRUITING

Des Moines, Iowa, 50309, United States
MU Health - University Hospital/Ellis Fischel Cancer Center
RECRUITING

Columbia, Missouri, 65212, United States
Maryland Proton Treatment Center
RECRUITING

Baltimore, Maryland, 21201, United States

Contact Email: •••••@•••••
Medical College of Wisconsin
RECRUITING

Milwaukee, Wisconsin, 53226, United States
Memorial Hospital East
RECRUITING

Shiloh, Illinois, 62269, United States
Montefiore Medical Center - Moses Campus
RECRUITING

The Bronx, New York, 10467, United States
Montefiore Medical Center-Einstein Campus
RECRUITING

The Bronx, New York, 10461, United States
Montefiore Medical Center-Weiler Hospital
RECRUITING

The Bronx, New York, 10461, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
RECRUITING

New York, New York, 10032, United States

Contact Email: •••••@•••••
Northwestern Medicine Cancer Center Delnor
RECRUITING

Geneva, Illinois, 60134, United States
Northwestern Medicine Cancer Center Kishwaukee
RECRUITING

DeKalb, Illinois, 60115, United States
Northwestern Medicine Cancer Center Warrenville
RECRUITING

Warrenville, Illinois, 60555, United States
Renown Regional Medical Center
RECRUITING

Reno, Nevada, 89502, United States
Saint Anthony Regional Hospital
RECRUITING

Carroll, Iowa, 51401, United States
Saint Mary's Hospital and Regional Medical Center
RECRUITING

Grand Junction, Colorado, 81501, United States
Siteman Cancer Center at Christian Hospital
RECRUITING

St Louis, Missouri, 63136, United States

Contact Email: •••••@•••••
Siteman Cancer Center at Saint Peters Hospital
RECRUITING

City of Saint Peters, Missouri, 63376, United States

Contact Email: •••••@•••••
Siteman Cancer Center at West County Hospital
RECRUITING

Creve Coeur, Missouri, 63141, United States

Contact Email: •••••@•••••
Siteman Cancer Center-South County
RECRUITING

St Louis, Missouri, 63129, United States

Contact Email: •••••@•••••
ThedaCare Regional Cancer Center
RECRUITING

Appleton, Wisconsin, 54911, United States

Contact Email: •••••@•••••
UC Irvine Health/Chao Family Comprehensive Cancer Center
RECRUITING

Orange, California, 92868, United States

Contact Email: •••••@•••••
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
RECRUITING

Irvine, California, 92612, United States

Contact Email: •••••@•••••
UI Health Care Mission Cancer and Blood - Ankeny Clinic
RECRUITING

Ankeny, Iowa, 50023, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
RECRUITING

Des Moines, Iowa, 50309, United States
UI Health Care Mission Cancer and Blood - Laurel Clinic
RECRUITING

Des Moines, Iowa, 50314, United States
UI Health Care Mission Cancer and Blood - Waukee Clinic
RECRUITING

Waukee, Iowa, 50263, United States
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
RECRUITING

Clive, Iowa, 50325, United States
UI Healthcare Mission Cancer and Blood - Pella
RECRUITING

Pella, Iowa, 50219, United States

Contact Email: •••••@•••••
UM Baltimore Washington Medical Center/Tate Cancer Center
RECRUITING

Glen Burnie, Maryland, 21061, United States
UM Upper Chesapeake Medical Center
RECRUITING

Bel Air, Maryland, 21014, United States
USC / Norris Comprehensive Cancer Center
RECRUITING

Los Angeles, California, 90033, United States
University of California Davis Comprehensive Cancer Center
RECRUITING

Sacramento, California, 95817, United States
University of Kansas Cancer Center
RECRUITING

Kansas City, Kansas, 66160, United States
University of Kansas Cancer Center - Briarcliff
RECRUITING

Kansas City, Missouri, 64116, United States
University of Kansas Cancer Center - Lee's Summit
RECRUITING

Lee's Summit, Missouri, 64064, United States
University of Kansas Cancer Center - North
RECRUITING

Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center-Overland Park
RECRUITING

Overland Park, Kansas, 66210, United States
University of Kansas Hospital-Westwood Cancer Center
RECRUITING

Westwood, Kansas, 66205, United States
University of Maryland/Greenebaum Cancer Center
RECRUITING

Baltimore, Maryland, 21201, United States
University of Oklahoma Health Sciences Center
RECRUITING

Oklahoma City, Oklahoma, 73104, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
RECRUITING

Madison, Wisconsin, 53718, United States

Contact Email: •••••@•••••
University of Wisconsin Carbone Cancer Center - Johnson Creek
RECRUITING

Johnson Creek, Wisconsin, 53038, United States

Contact Email: •••••@•••••
University of Wisconsin Carbone Cancer Center - University Hospital
RECRUITING

Madison, Wisconsin, 53792, United States

Contact Email: •••••@•••••
Washington University School of Medicine
RECRUITING

St Louis, Missouri, 63110, United States

Contact Email: •••••@•••••

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