Glioblastoma, IDH-WildtypePhase 3NCT07452458
Temporally-Modulated Pulsed Radiation Therapy Versus Standard Radiation Therapy for the Treatment of Newly Diagnosed, IDH Wildtype, MGMT-Unmethylated Glioblastoma
A Phase 3 study testing Biospecimen Collection, Computed Tomography and Magnetic Resonance Imaging in people with Glioblastoma, IDH-Wildtype and MGMT-Unmethylated Glioblastoma, run by NRG Oncology at 54 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, IDH-Wildtype, MGMT-Unmethylated Glioblastoma
- What is being tested?
- Biospecimen Collection, Computed Tomography and Magnetic Resonance Imaging
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 398 participants
- Where
- 54 sitesUnited States
- Study dates
- 16 Jul 2026to 15 Jul 2035
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 32Show fewer
- 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.
Who cannot join
None listed.
Trial locations and contacts
54 sites in 1 country. Contact the study team or a site near you to ask about taking part.
54 sites in 1 country
United States54 sites, 54 recruiting
- Recruiting
Alton Memorial Hospital
Alton, Illinois, 62002
Site Public Contact, 618-463-7323
Jiayi Huang
- Recruiting
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023
Site Public Contact, 515-241-3305
Seema Harichand-Herdt
- Recruiting
ThedaCare Regional Cancer Center
Appleton, Wisconsin, 54911
Site Public Contact, 920-364-3604, ResearchDept@thedacare.org
Joseph A. Bovi
- Recruiting
Maryland Proton Treatment Center
Baltimore, Maryland, 21201
Site Public Contact, 410-369-5226, info@mdproton.com
Mark V. Mishra
- Recruiting
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
Site Public Contact, 800-888-8823
Mark V. Mishra
- Recruiting
UM Upper Chesapeake Medical Center
Bel Air, Maryland, 21014
Site Public Contact, 443-643-3010
Mark V. Mishra
- Recruiting
Saint Anthony Regional Hospital
Carroll, Iowa, 51401
Site Public Contact, 515-689-7658, sbenson@iora.org
Seema Harichand-Herdt
- Recruiting
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Jiayi Huang
- Recruiting
Case Western Reserve University
Cleveland, Ohio, 44106
Site Public Contact, 800-641-2422, CTUReferral@UHhospitals.org
Haley K. Perlow
- Recruiting
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325
Site Public Contact, 515-241-3305
Seema Harichand-Herdt
- Recruiting
MU Health - University Hospital/Ellis Fischel Cancer Center
Columbia, Missouri, 65212
Site Public Contact, 573-882-7440
Mohamed Abdelhakiem
- Recruiting
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Jiayi Huang
- Recruiting
Decatur Memorial Hospital
Decatur, Illinois, 62526
Site Public Contact, 217-876-4762, morganthaler.jodi@mhsil.com
Bryan A. Faller
- Recruiting
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115
Site Public Contact, 630-352-5360, Donald.Smith3@nm.org
Vinai Gondi
- Recruiting
Iowa Methodist Medical Center
Des Moines, Iowa, 50309
Site Public Contact, 515-241-6727
Seema Harichand-Herdt
- Recruiting
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309
Site Public Contact, 515-241-3305
Seema Harichand-Herdt
- Recruiting
Broadlawns Medical Center
Des Moines, Iowa, 50314
Site Public Contact, 515-282-2200
Seema Harichand-Herdt
- Recruiting
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314
Site Public Contact, 515-241-3305
Seema Harichand-Herdt
- Recruiting
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134
Site Public Contact, 630-352-5360, Donald.Smith3@nm.org
Vinai Gondi
- Recruiting
UM Baltimore Washington Medical Center/Tate Cancer Center
Glen Burnie, Maryland, 21061
Site Public Contact, 410-553-8100
Mark V. Mishra
- Recruiting
Saint Mary's Hospital and Regional Medical Center
Grand Junction, Colorado, 81501
Site Public Contact, 303-777-2663, ccrp@co-cancerresearch.org
Lucas Gilbride
- Recruiting
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Xiao-Tang Kong
- Recruiting
University of Wisconsin Carbone Cancer Center - Johnson Creek
Johnson Creek, Wisconsin, 53038
Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu
Brett A. Morris
- Recruiting
University of Kansas Cancer Center
Kansas City, Kansas, 66160
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Danielle Cunningham
- Recruiting
University of Kansas Cancer Center - Briarcliff
Kansas City, Missouri, 64116
Site Public Contact, 913-588-3671
Danielle Cunningham
- Recruiting
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Danielle Cunningham
- Recruiting
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Danielle Cunningham
- Recruiting
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Site Public Contact, 323-865-0451
Adam Garsa
- Recruiting
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718
Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu
Brett A. Morris
- Recruiting
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu
Brett A. Morris
- Recruiting
Froedtert Menomonee Falls Hospital
Menomonee Falls, Wisconsin, 53051
Site Public Contact, 262-257-5100
Michael W. Straza
- Recruiting
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Site Public Contact, 414-805-3666
Michael W. Straza
- Recruiting
Froedtert and MCW Moorland Reserve Health Center
New Berlin, Wisconsin, 53151
Site Public Contact, 414-805-0505
Michael W. Straza
- Recruiting
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Site Public Contact, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu
Tony J. Wang
- Recruiting
Cancer Care Center of O'Fallon
O'Fallon, Illinois, 62269
Site Public Contact, 217-876-4762, morganthaler.jodi@mhsil.com
Bryan A. Faller
- Recruiting
HSHS Saint Elizabeth's Hospital
O'Fallon, Illinois, 62269
Site Public Contact, 217-876-4762, morganthaler.jodi@mhsil.com
Bryan A. Faller
- Recruiting
Drexel Town Square Health Center
Oak Creek, Wisconsin, 53154
Site Public Contact, 414-805-0505
Michael W. Straza
- Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Site Public Contact, 405-271-8777, ou-clinical-trials@ouhsc.edu
Shearwood McClelland
- Recruiting
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Xiao-Tang Kong
- Recruiting
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Danielle Cunningham
- Recruiting
UI Healthcare Mission Cancer and Blood - Pella
Pella, Iowa, 50219
Site Public Contact, 515-282-2921, trials@missioncancer.com
Seema Harichand-Herdt
- Recruiting
Renown Regional Medical Center
Reno, Nevada, 89502
Site Public Contact, 775-982-5050, Renown-CRD@renown.org
Suchit H. Patel
- Recruiting
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Site Public Contact, 916-734-3089
Ruben C. Fragoso
- Recruiting
Memorial Hospital East
Shiloh, Illinois, 62269
Site Public Contact, 314-747-9912, dschwab@wustl.edu
Jiayi Huang
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Jiayi Huang
- Recruiting
Siteman Cancer Center-South County
St Louis, Missouri, 63129
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Jiayi Huang
- Recruiting
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Jiayi Huang
- Recruiting
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461
Site Public Contact, 718-379-6866, eskwak@montefiore.org
Justin Tang
- Recruiting
Montefiore Medical Center-Weiler Hospital
The Bronx, New York, 10461
Site Public Contact, 718-379-6866, eskwak@montefiore.org
Justin Tang
- Recruiting
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
Site Public Contact, 718-379-6866, eskwak@montefiore.org
Justin Tang
- Recruiting
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555
Site Public Contact, 630-352-5360, Donald.Smith3@nm.org
Vinai Gondi
- Recruiting
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa, 50263
Site Public Contact, 515-241-3305
Seema Harichand-Herdt
- Recruiting
Froedtert West Bend Hospital/Kraemer Cancer Center
West Bend, Wisconsin, 53095
Site Public Contact, 414-805-0505
Michael W. Straza
- Recruiting
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Danielle Cunningham
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- 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:
- 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).
- 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.
- Being tested
- Biospecimen Collection, Computed Tomography, Magnetic Resonance Imaging, Questionnaire Administration, Radiation Therapy
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo collection of blood
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
Questionnaire AdministrationOther
Ancillary studies
Radiation TherapyRadiation
Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate
Undergo standard RT
TemozolomideDrug
Also called CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831
Given PO
Temporally-modulated Pulsed Radiation TherapyRadiation
Also called TMPRT
Undergo TMPRT
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Other: Questionnaire Administration; Radiation: Radiation Therapy; Drug: 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. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Other: Questionnaire Administration; Drug: Temozolomide; Radiation: Temporally-modulated Pulsed Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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)
Will be measured by the HVLT-R, COWA, and TMT. A mixed effects model will be used to assess changes of standardized neurocognitive scores across time using all available data while adjusting for stratification variables and other baseline characteristics. Fixed effects will consist of treatment arm, baseline score, Recursive Partitioning Analysis (RPA) class, fractionation, tumor treating fields therapy (TTFields), steroid use, anti-seizure medication use as well as the interaction between time and treatment arm.
Measured: Up to 9 months after completion of RT
NCF across time
Will be measured by the HVLT-R, COWA, and TMT. A mixed effects model will be used to assess changes of standardized neurocognitive scores across time using all available data while adjusting for stratification variables and other baseline characteristics. Fixed effects will consist of treatment arm, baseline score, RPA class, fractionation, TTFields, steroid use, anti-seizure medication use as well as the interaction between time and treatment arm.
Measured: Up to 9 months after completion of RT
Quality of Life (QoL)
The Functional Assessment of Cancer Therapy - Brain (FACT-Br) total score will be used to measure overall QoL. Scores will be analyzed similarly to the individual NCF tests as described above. Briefly, mixed effects models will be performed. If the time by treatment interaction is significant, then tests will be conducted at each timepoint, within the model framework. Missing data will also be assessed and sensitivity analyses performed as needed.
Measured: Up to 9 months after completion of RT
Patient-reported cognitive outcomes (PRCO)
Nine items make up the FACT-Br-Cognitive Index score that will be used to assess PRCO. Scores will be analyzed similarly to the individual NCF tests as described above. Briefly, mixed effects models will be performed. If the time by treatment interaction is significant, then tests will be conducted at each timepoint, within the model framework. Missing data will also be assessed and sensitivity analyses performed as needed.
Measured: Up to 9 months after completion of RT
Frailty
The primary frailty endpoint is the Deficit Accumulation Frailty Index (DAFI) which requires at least 30 items in the score for it to be valid (Searle 2008). Thus, the NCF score will be removed from the DAFI score calculation since the primary endpoint of the trial is NCF. At least 90% of the DAFI must be completed to be included in the analysis. The continuous DAFI score will be analyzed similarly to the individual NCF tests as described above in the section. Briefly, mixed effects models will be performed. If the time by treatment interaction is significant, then tests will be conducted at each timepoint, within the model framework. Missing data will also be assessed and sensitivity analyses performed as needed.
Measured: Up to 9 months after completion of RT
Overall survival (OS)
OS rates will be estimated using the Kaplan-Meier method, and differences between treatment arms will be tested using the log rank test.
Measured: From the date of randomization to the date of death, or, otherwise, the last follow-up date on which the patient was reported alive, assessed up to 9 months after completion of RT
Progression-free survival (PFS)
PFS rates will be estimated using the Kaplan-Meier method, and differences between treatment arms will be tested using the log rank test.
Measured: From the date of randomization to the date of progression or death, whichever occurs first, or the last follow-up date on which the patient was reported alive, assessed up to 9 months after completion of RT
Incidence of adverse events (AEs)
AEs will be evaluated using Common Terminology Criteria for Adverse Events version 5.0. Counts of all AEs by grade will be provided by treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm. The rate of grade 3+ AEs and the rate of grade 3+ central nervous system necrosis, stroke, and intra-cranial hemorrhage will be compared between treatment arms using a Chi-square test at a two-sided significance level of 0.05.
Measured: Up to 9 months after completion of RT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2026
- Study start16 Jul 2026
- Primary completion15 Jan 2030 (estimated)
- Study completion15 Jul 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma, IDH-WildtypeStudies of the same condition, open and under way.
- More trials run by NRG OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 398 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NRG Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jiayi Huang, Principal investigator, NRG Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07452458
- Sponsor's protocol ID
- NRG-CC017
- Other IDs
- NCI-2025-09197, NRG-CC017, NRG-CC017, IVR-50415, UG1CA189867
- Status last verified
- Sep 2026
- First submitted
- 17 Feb 2026
- Last updated
- 10 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.