Recruiting
Phase 3

TMPRT vs. Standard Radiation

Sponsor:

NRG Oncology

Code:

NCT07452458

Conditions

Glioblastoma, IDH-Wildtype

MGMT-Unmethylated Glioblastoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Questionnaire Administration

Radiation Therapy

Study Details

Brief summary:

This phase III trial compares temporally-modulated pulsed radiation therapy versus standard radiation therapy in treating patients with newly diagnosed, IDH wildtype, MGMT-unmethylated glioblastoma. After completion of surgery, the standard of care for glioblastoma is radiation therapy. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. For older and frail patients, standard treatment also includes the chemotherapy drug temozolomide. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill tumor cells and slow down or stop tumor growth. Approximately 70% of glioblastoma patients have MGMT-unmethylated status. MGMT unmethylated tumors are less likely to respond to temozolomide chemotherapy, so there is more reliance on radiation therapy to kill the tumor cells. Recent clinical trials studying new therapies for MGMT-unmethylated glioblastoma have failed to improve outcomes over temozolomide. These recent studies also indicate that 80% of patients experience a decline in memory and thinking function after treatment. TMPRT differs from standard radiation therapy by delivering the same amount of radiation dose in 10-13 "pulses" with 3-minute breaks between pulses. TMPRT with temozolomide may work better than standard radiation therapy with temozolomide in increasing survival, as well as improving memory and thinking function in patients with newly diagnosed, IDH wildtype, MGMT-unmethylated glioblastoma.

Conditions

Glioblastoma, IDH-Wildtype

MGMT-Unmethylated Glioblastoma

Study ID

NCT07452458

Start date

Jul 16, 2026

Status verified date

Sep, 2026

Completion date

Jul 15, 2031

Anticipated

Primary completion date

Jan 15, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

398 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Supportive Care

Interventions and Outcome Measures

Arms

active comparator: Arm 1 (standard RT, temozolomide)

CONCURRENT TREATMENT (CYCLE 1): Patients receive standard RT over 12-15 minutes daily, 5 days a week, for 3 or 6 weeks. Patients also receive temozolomide PO QD on days 1-21 or 1-42. Cycle 1 treatment continues for 21 or 42 days in in the absence of disease progression or unacceptable toxicity.

ADJUVANT TREATMENT (CYCLES 2+): Approximately 1 month after completion of standard RT, patients receive temozolomide PO QD on days 1-5 of each cycle. Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

Patients also undergo CT or MRI scans, as well as optional blood sample collection throughout the trial.

experimental: Arm 2 (TMPRT, temozolomide)

CONCURRENT TREATMENT (CYCLE 1): Patients receive TMPRT, delivered as 10-13 "pulses" over 30-40 minutes each with a 3 minute break in between, 5 days a week for 3 or 6 weeks. Patients also receive temozolomide PO QD on days 1-21 or 1-42. Cycle 1 treatment continues for 21 or 42 days in in the absence of disease progression or unacceptable toxicity.

ADJUVANT TREATMENT (CYCLES 2+): Approximately 1 month after completion of standard RT, patients receive temozolomide PO QD on days 1-5 of each cycle. Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

Patients also undergo CT or MRI scans, as well as optional blood sample collection throughout the trial.

Interventions

Biospecimen Collection

Undergo collection of blood

Computed Tomography

Undergo CT

Magnetic Resonance Imaging

Undergo MRI

Questionnaire Administration

Ancillary studies

Radiation Therapy

Undergo standard RT

Temozolomide

Given PO

Temporally-modulated Pulsed Radiation Therapy

Undergo TMPRT

Primary outcome measure

  • Neurocognitive function (NCF) [ Time Frame: Up to 9 months after completion of radiation therapy (RT) ]

Central Contacts and Locations

Locations

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Recruiting

Irvine, California, United States, 92612

Contacts

Site Public Contact

877-827-8839ucstudy@uci.edu

Principal Investigator:

Xiao-Tang Kong

USC / Norris Comprehensive Cancer Center

Recruiting

Los Angeles, California, United States, 90033

Contacts

Site Public Contact

323-865-0451

Principal Investigator:

Adam Garsa

UC Irvine Health/Chao Family Comprehensive Cancer Center

Recruiting

Orange, California, United States, 92868

Contacts

Site Public Contact

877-827-8839ucstudy@uci.edu

Principal Investigator:

Xiao-Tang Kong

University of California Davis Comprehensive Cancer Center

Recruiting

Sacramento, California, United States, 95817

Contacts

Site Public Contact

916-734-3089

Principal Investigator:

Ruben C. Fragoso

Saint Mary's Hospital and Regional Medical Center

Recruiting

Grand Junction, Colorado, United States, 81501

Contacts

Site Public Contact

303-777-2663ccrp@co-cancerresearch.org

Principal Investigator:

Lucas Gilbride

Alton Memorial Hospital

Recruiting

Alton, Illinois, United States, 62002

Contacts

Site Public Contact

618-463-7323

Principal Investigator:

Jiayi Huang

Decatur Memorial Hospital

Recruiting

Decatur, Illinois, United States, 62526

Contacts

Site Public Contact

217-876-4762morganthaler.jodi@mhsil.com

Principal Investigator:

Bryan A. Faller

Northwestern Medicine Cancer Center Kishwaukee

Recruiting

DeKalb, Illinois, United States, 60115

Contacts

Site Public Contact

630-352-5360Donald.Smith3@nm.org

Principal Investigator:

Vinai Gondi

Northwestern Medicine Cancer Center Delnor

Recruiting

Geneva, Illinois, United States, 60134

Contacts

Site Public Contact

630-352-5360Donald.Smith3@nm.org

Principal Investigator:

Vinai Gondi

Cancer Care Center of O'Fallon

Recruiting

O'Fallon, Illinois, United States, 62269

Contacts

Site Public Contact

217-876-4762morganthaler.jodi@mhsil.com

Principal Investigator:

Bryan A. Faller

HSHS Saint Elizabeth's Hospital

Recruiting

O'Fallon, Illinois, United States, 62269

Contacts

Site Public Contact

217-876-4762morganthaler.jodi@mhsil.com

Principal Investigator:

Bryan A. Faller

Memorial Hospital East

Recruiting

Shiloh, Illinois, United States, 62269

Contacts

Site Public Contact

314-747-9912dschwab@wustl.edu

Principal Investigator:

Jiayi Huang

Northwestern Medicine Cancer Center Warrenville

Recruiting

Warrenville, Illinois, United States, 60555

Contacts

Site Public Contact

630-352-5360Donald.Smith3@nm.org

Principal Investigator:

Vinai Gondi

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Recruiting

Ankeny, Iowa, United States, 50023

Contacts

Site Public Contact

515-241-3305

Principal Investigator:

Seema Harichand-Herdt

Saint Anthony Regional Hospital

Recruiting

Carroll, Iowa, United States, 51401

Contacts

Site Public Contact

515-689-7658sbenson@iora.org

Principal Investigator:

Seema Harichand-Herdt

UI Health Care Mission Cancer and Blood - West Des Moines Clinic

Recruiting

Clive, Iowa, United States, 50325

Contacts

Site Public Contact

515-241-3305

Principal Investigator:

Seema Harichand-Herdt

Iowa Methodist Medical Center

Recruiting

Des Moines, Iowa, United States, 50309

Contacts

Site Public Contact

515-241-6727

Principal Investigator:

Seema Harichand-Herdt

UI Health Care Mission Cancer and Blood - Des Moines Clinic

Recruiting

Des Moines, Iowa, United States, 50309

Contacts

Site Public Contact

515-241-3305

Principal Investigator:

Seema Harichand-Herdt

Broadlawns Medical Center

Recruiting

Des Moines, Iowa, United States, 50314

Contacts

Site Public Contact

515-282-2200

Principal Investigator:

Seema Harichand-Herdt

UI Health Care Mission Cancer and Blood - Laurel Clinic

Recruiting

Des Moines, Iowa, United States, 50314

Contacts

Site Public Contact

515-241-3305

Principal Investigator:

Seema Harichand-Herdt

UI Healthcare Mission Cancer and Blood - Pella

Recruiting

Pella, Iowa, United States, 50219

Contacts

Site Public Contact

515-282-2921trials@missioncancer.com

Principal Investigator:

Seema Harichand-Herdt

UI Health Care Mission Cancer and Blood - Waukee Clinic

Recruiting

Waukee, Iowa, United States, 50263

Contacts

Site Public Contact

515-241-3305

Principal Investigator:

Seema Harichand-Herdt

University of Kansas Cancer Center

Recruiting

Kansas City, Kansas, United States, 66160

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Danielle Cunningham

University of Kansas Cancer Center-Overland Park

Recruiting

Overland Park, Kansas, United States, 66210

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Danielle Cunningham

University of Kansas Hospital-Westwood Cancer Center

Recruiting

Westwood, Kansas, United States, 66205

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Danielle Cunningham

Maryland Proton Treatment Center

Recruiting

Baltimore, Maryland, United States, 21201

Contacts

Site Public Contact

410-369-5226info@mdproton.com

Principal Investigator:

Mark V. Mishra

University of Maryland/Greenebaum Cancer Center

Recruiting

Baltimore, Maryland, United States, 21201

Contacts

Site Public Contact

800-888-8823

Principal Investigator:

Mark V. Mishra

UM Upper Chesapeake Medical Center

Recruiting

Bel Air, Maryland, United States, 21014

Contacts

Site Public Contact

443-643-3010

Principal Investigator:

Mark V. Mishra

UM Baltimore Washington Medical Center/Tate Cancer Center

Recruiting

Glen Burnie, Maryland, United States, 21061

Contacts

Site Public Contact

410-553-8100

Principal Investigator:

Mark V. Mishra

Siteman Cancer Center at Saint Peters Hospital

Recruiting

City of Saint Peters, Missouri, United States, 63376

Contacts

Site Public Contact

800-600-3606info@siteman.wustl.edu

Principal Investigator:

Jiayi Huang

MU Health - University Hospital/Ellis Fischel Cancer Center

Recruiting

Columbia, Missouri, United States, 65212

Contacts

Site Public Contact

573-882-7440

Principal Investigator:

Mohamed Abdelhakiem

Siteman Cancer Center at West County Hospital

Recruiting

Creve Coeur, Missouri, United States, 63141

Contacts

Site Public Contact

800-600-3606info@siteman.wustl.edu

Principal Investigator:

Jiayi Huang

University of Kansas Cancer Center - Briarcliff

Recruiting

Kansas City, Missouri, United States, 64116

Contacts

Site Public Contact

913-588-3671

Principal Investigator:

Danielle Cunningham

University of Kansas Cancer Center - North

Recruiting

Kansas City, Missouri, United States, 64154

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Danielle Cunningham

University of Kansas Cancer Center - Lee's Summit

Recruiting

Lee's Summit, Missouri, United States, 64064

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Danielle Cunningham

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Site Public Contact

800-600-3606info@siteman.wustl.edu

Principal Investigator:

Jiayi Huang

Siteman Cancer Center-South County

Recruiting

St Louis, Missouri, United States, 63129

Contacts

Site Public Contact

800-600-3606info@siteman.wustl.edu

Principal Investigator:

Jiayi Huang

Siteman Cancer Center at Christian Hospital

Recruiting

St Louis, Missouri, United States, 63136

Contacts

Site Public Contact

800-600-3606info@siteman.wustl.edu

Principal Investigator:

Jiayi Huang

Renown Regional Medical Center

Recruiting

Reno, Nevada, United States, 89502

Contacts

Site Public Contact

775-982-5050Renown-CRD@renown.org

Principal Investigator:

Suchit H. Patel

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

Recruiting

New York, New York, United States, 10032

Contacts

Site Public Contact

212-342-5162cancerclinicaltrials@cumc.columbia.edu

Principal Investigator:

Tony J. Wang

Montefiore Medical Center-Einstein Campus

Recruiting

The Bronx, New York, United States, 10461

Contacts

Site Public Contact

718-379-6866eskwak@montefiore.org

Principal Investigator:

Justin Tang

Montefiore Medical Center-Weiler Hospital

Recruiting

The Bronx, New York, United States, 10461

Contacts

Site Public Contact

718-379-6866eskwak@montefiore.org

Principal Investigator:

Justin Tang

Montefiore Medical Center - Moses Campus

Recruiting

The Bronx, New York, United States, 10467

Contacts

Site Public Contact

718-379-6866eskwak@montefiore.org

Principal Investigator:

Justin Tang

Case Western Reserve University

Recruiting

Cleveland, Ohio, United States, 44106

Contacts

Site Public Contact

800-641-2422CTUReferral@UHhospitals.org

Principal Investigator:

Haley K. Perlow

University of Oklahoma Health Sciences Center

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Contacts

Site Public Contact

405-271-8777ou-clinical-trials@ouhsc.edu

Principal Investigator:

Shearwood McClelland

ThedaCare Regional Cancer Center

Recruiting

Appleton, Wisconsin, United States, 54911

Contacts

Site Public Contact

920-364-3604ResearchDept@thedacare.org

Principal Investigator:

Joseph A. Bovi

University of Wisconsin Carbone Cancer Center - Johnson Creek

Recruiting

Johnson Creek, Wisconsin, United States, 53038

Contacts

Site Public Contact

800-622-8922clinicaltrials@cancer.wisc.edu

Principal Investigator:

Brett A. Morris

University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

Recruiting

Madison, Wisconsin, United States, 53718

Contacts

Site Public Contact

800-622-8922clinicaltrials@cancer.wisc.edu

Principal Investigator:

Brett A. Morris

University of Wisconsin Carbone Cancer Center - University Hospital

Recruiting

Madison, Wisconsin, United States, 53792

Contacts

Site Public Contact

800-622-8922clinicaltrials@cancer.wisc.edu

Principal Investigator:

Brett A. Morris

Froedtert Menomonee Falls Hospital

Recruiting

Menomonee Falls, Wisconsin, United States, 53051

Contacts

Site Public Contact

262-257-5100

Principal Investigator:

Michael W. Straza

Medical College of Wisconsin

Recruiting

Milwaukee, Wisconsin, United States, 53226

Contacts

Site Public Contact

414-805-3666

Principal Investigator:

Michael W. Straza

Froedtert and MCW Moorland Reserve Health Center

Recruiting

New Berlin, Wisconsin, United States, 53151

Contacts

Site Public Contact

414-805-0505

Principal Investigator:

Michael W. Straza

Drexel Town Square Health Center

Recruiting

Oak Creek, Wisconsin, United States, 53154

Contacts

Site Public Contact

414-805-0505

Principal Investigator:

Michael W. Straza

Froedtert West Bend Hospital/Kraemer Cancer Center

Recruiting

West Bend, Wisconsin, United States, 53095

Contacts

Site Public Contact

414-805-0505

Principal Investigator:

Michael W. Straza

More Information

Sponsor

NRG Oncology

Last update posted

Sep 9, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by NRG Oncology on 2026-09-09.