Ignite Creation Date:
2026-03-26 @ 3:18 PM
Ignite Modification Date:
2026-03-31 @ 7:41 AM
Study NCT ID:
NCT07452458
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-03-05
First Post:
2026-02-17
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Temporally-Modulated Pulsed Radiation Therapy Versus Standard Radiation Therapy for the Treatment of Newly Diagnosed, IDH Wildtype, MGMT-Unmethylated Glioblastoma
Sponsor:
NRG Oncology
Organization:
Study Overview
Official Title:
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
Status:
NOT_YET_RECRUITING
Status Verified Date:
2026-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
Detailed Description:
PRIMARY OBJECTIVE:
I. To determine whether TMPRT concurrently with TMZ can significantly improve time to neurocognitive function (NCF) failure compared to standard radiation therapy (RT) with temozolomide for patients with MGMT-unmethylated GBM.
SECONDARY OBJECTIVES:
I. To determine whether TMPRT can significantly improve time to NCF failure for the subset of older patients (age ≥ 65) with MGMT-unmethylated GBM.
II. To evaluate between arm differences in NCF across time. III. To evaluate whether TMPRT prolongs overall survival (OS) compared to the control arm.
IV. To determine if progression free survival (PFS) is prolonged after TMPRT compared to the control arm.
V. To determine if TMPRT improves quality of life (QoL), compared to the control arm, as measured by the Functional Assessment of Cancer Therapy - Brain (FACT-Br) Total Score.
VI. To determine if TMPRT improves patient-reported cognitive outcome (PRCO) compared to the control arm, as measured by the Functional Assessment of Cancer Therapy - Brain Cognitive Index (FACT-Br- CI).
VII. To determine the impact of TMPRT on longitudinal changes in frailty after treatment compared to the control arm, as measured by the Deficit Accumulation Frailty Index (DAFI) derived from the Practical Geriatric Assessment (PGA).
VIII. To evaluate if TMPRT reduces toxicity compared to the control arm.
EXPLORATORY OBJECTIVES:
I. To evaluate the impact of TMPRT on functional, social, and emotional QoL compared to the control arm, as measured by the FACT-Br.
II. To evaluate the impact of TMPRT on longitudinal changes of specific geriatric assessment subscales compared to the control arm, as measured by the PGA.
III. To evaluate the impact of TMPRT on treatment burden during RT compared to the control arm, as measured by the FACT-Br Physical Wellbeing subscale (FACT-Br PWB).
IV. To investigate if TMPRT results in less white matter injury on post-treatment magnetic resonance imaging (MRI).
V. To collect blood samples for future translational studies. VI. To correlate NCF with QoL and frailty. VII. To determine if baseline NCF, QoL, and frailty are associated with OS. VIII. To correlate adverse events with baseline frailty and specific geriatric assessment subscales.
IX. To determine the concordance between institutional and central MGMT promoter status.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1:
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 orally (PO) once daily (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.
ARM 2:
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.
All patients also undergo computed tomography (CT) or MRI scans, as well as optional blood sample collection throughout the trial.
After completion of study treatment, patients are followed at months 1, 3, 5, 7, 9, and 12, then annually for 4 years.
I. To determine whether TMPRT concurrently with TMZ can significantly improve time to neurocognitive function (NCF) failure compared to standard radiation therapy (RT) with temozolomide for patients with MGMT-unmethylated GBM.
SECONDARY OBJECTIVES:
I. To determine whether TMPRT can significantly improve time to NCF failure for the subset of older patients (age ≥ 65) with MGMT-unmethylated GBM.
II. To evaluate between arm differences in NCF across time. III. To evaluate whether TMPRT prolongs overall survival (OS) compared to the control arm.
IV. To determine if progression free survival (PFS) is prolonged after TMPRT compared to the control arm.
V. To determine if TMPRT improves quality of life (QoL), compared to the control arm, as measured by the Functional Assessment of Cancer Therapy - Brain (FACT-Br) Total Score.
VI. To determine if TMPRT improves patient-reported cognitive outcome (PRCO) compared to the control arm, as measured by the Functional Assessment of Cancer Therapy - Brain Cognitive Index (FACT-Br- CI).
VII. To determine the impact of TMPRT on longitudinal changes in frailty after treatment compared to the control arm, as measured by the Deficit Accumulation Frailty Index (DAFI) derived from the Practical Geriatric Assessment (PGA).
VIII. To evaluate if TMPRT reduces toxicity compared to the control arm.
EXPLORATORY OBJECTIVES:
I. To evaluate the impact of TMPRT on functional, social, and emotional QoL compared to the control arm, as measured by the FACT-Br.
II. To evaluate the impact of TMPRT on longitudinal changes of specific geriatric assessment subscales compared to the control arm, as measured by the PGA.
III. To evaluate the impact of TMPRT on treatment burden during RT compared to the control arm, as measured by the FACT-Br Physical Wellbeing subscale (FACT-Br PWB).
IV. To investigate if TMPRT results in less white matter injury on post-treatment magnetic resonance imaging (MRI).
V. To collect blood samples for future translational studies. VI. To correlate NCF with QoL and frailty. VII. To determine if baseline NCF, QoL, and frailty are associated with OS. VIII. To correlate adverse events with baseline frailty and specific geriatric assessment subscales.
IX. To determine the concordance between institutional and central MGMT promoter status.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1:
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 orally (PO) once daily (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.
ARM 2:
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.
All patients also undergo computed tomography (CT) or MRI scans, as well as optional blood sample collection throughout the trial.
After completion of study treatment, patients are followed at months 1, 3, 5, 7, 9, and 12, then annually for 4 years.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: