NCT07452458|RecruitingPhase 3DMC

Temporally-Modulated Pulsed Radiation Therapy Versus Standard Radiation Therapy for the Treatment of Newly Diagnosed, IDH Wildtype, MGMT-Unmethylated Glioblastoma

A Randomized Phase III Study Comparing Temporally-Modulated Pulsed Radiation Therapy (TMPRT) Versus Standard Radiation Therapy With Temozolomide for Adults With Newly Diagnosed MGMT-Unmethylated Glioblastoma

NRG Oncology ClinicalTrials.gov

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4 other identifiers

NRG-CC017NCI-2025-09197IVR-50415UG1CA189867

Study Type

interventional

Target

398

Locations

1 country

Sites

Timeline

RegisteredMar 2026

StartedJul 2026

CompletionJul 2035

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

398

participants targeted

Target at P50-P75 for phase_3

Timeline

107mo left

Started Jul 2026

Longer than P75 for phase_3

Geographic Reach

1 country

54 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

9 years study duration

Study Progress2%

Jul 2026Jul 2035

First Submitted

Initial submission to the registry

February 17, 2026

Completed

16 days until next milestone

First Posted

Study publicly available on registry

March 5, 2026

Completed

4 months until next milestone

Study Start

First participant enrolled

July 16, 2026

Completed

3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 15, 2030

Expected

5.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 15, 2035

Last Updated

September 10, 2026

Status Verified

September 1, 2026

Enrollment Period

3.5 years

First QC Date

February 17, 2026

Last Update Submit

September 9, 2026

Conditions

Glioblastoma, IDH-Wildtype MGMT-Unmethylated Glioblastoma

Outcome Measures

Primary Outcomes (1)

Neurocognitive function (NCF)
This endpoint will be evaluated using each NCF testing interval. NCF failure is defined as a decline in NCF using the reliable change index (RCI) on at least one of the following tests: Hopkins Verbal Learning Test - Revised (HVLT-R) Total Recall, HVLT-R Delayed Recall, HVLT-R Delayed Recognition, Trail Making Test (TMT) Part A, TMT Part B, or Controlled Oral Word Association (COWA). The cumulative incidence approach will be used to estimate the time to neurocognitive failure to account for the competing risk of death. Gray's test will assess statistically significant differences in the distribution of NCF failure times (Gray 1988).
Up to 9 months after completion of radiation therapy (RT)

Secondary Outcomes (8)

Time to NCF failure in the subset of older patients (≤ 65 years)
Up to 9 months after completion of RT
NCF across time
Up to 9 months after completion of RT
Quality of Life (QoL)
Up to 9 months after completion of RT
Patient-reported cognitive outcomes (PRCO)
Up to 9 months after completion of RT
Frailty
Up to 9 months after completion of RT
+3 more secondary outcomes

Study Arms (2)

Arm 1 (standard RT, temozolomide)

ACTIVE COMPARATOR

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.

Procedure: Biospecimen CollectionProcedure: Computed TomographyProcedure: Magnetic Resonance ImagingOther: Questionnaire AdministrationRadiation: Radiation TherapyDrug: Temozolomide

Arm 2 (TMPRT, temozolomide)

EXPERIMENTAL

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.

Procedure: Biospecimen CollectionProcedure: Computed TomographyProcedure: Magnetic Resonance ImagingOther: Questionnaire AdministrationDrug: TemozolomideRadiation: Temporally-modulated Pulsed Radiation Therapy