Short Course Radiotherapy for the Treatment of Patients With Glioblastoma, SAGA Study

NCT ID: NCT05781321

Last Updated: 2026-02-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

170 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-03-23

Study Completion Date

2028-07-02

Brief Summary

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This phase II trial compares the effect of short course radiotherapy (RT) to standard course RT for the treatment of patients diagnosed with glioblastoma (GBM). The researchers want to learn whether the shorter course treatment is non-inferior (not worse than the standard of care), for patients with GBM. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Short course radiotherapy delivers higher doses of radiation over a shorter period of time and may kill more tumor cells and have fewer side effects.

Detailed Description

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PRIMARY OBJECTIVE:

I. To demonstrate non-inferior 12-month overall survival (OS) of patients with GBM treated with dose escalated hypofractionated radiotherapy compared to standard of care.

SECONDARY OBJECTIVES:

I. To demonstrate the safety of short-course radiotherapy via physician-reported grade (G) 3+ toxicity.

II. To explore patient-reported outcomes to demonstrate favorable quality of life with short-course radiotherapy for GBM.

III. To analyze the impact of shortening the treatment duration on treatment related lymphopenia and absolute lymphocyte counts.

EXPLORATORY OBJECTIVES:

I. To determine the cost-effectiveness of the 5-fraction treatment regimen compared to standard of care.

II. To explore the impact on the immune system with the 5-fraction treatment regimen. Immune phenotyping will be assessed by Flow Cytometry and cytometry by flight (CyTOF).

III. To analyze series of cytokine levels over time. IV. To assess patterns of failure, specifically focusing on differences in volume delineation via Fluorodopa F 18 (FDOPA) and magnetic resonance imaging (MRI) and recurrences in-field versus (vs.) out of field.

V. To conduct a subgroup analysis for just patients =\< 65 cc. VI. To conduct a subgroup analysis for just patients with and without tumor treating fields.

VII. To analyze patient demographic data compared to historical controls to determine whether the short-course treatment regimen improves access to underserved populations.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients undergo short course RT for 5-10 fractions over 1-2 weeks on study. Patients also receive temozolomide orally (PO) on days 1-5 every 28 days during radiation therapy. Starting one month post-radiation, patients continue temozolomide on days 1-5 every 28 days for up to 5 adjuvant cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients undergo standard course RT for 15-30 fractions over 3-6 weeks on study. Patients also receive temozolomide PO daily (QD) concurrently with radiation therapy and for up to 6 adjuvant cycles in the absence of disease progression or unacceptable toxicity.

All patients undergo positron emission tomography/computed tomography (PET/CT) with 18-F-DOPA administered intravenously (IV) prior to RT on study, and undergo MRI prior to RT and throughout the trial. Patients may optionally undergo blood sample collection during screening and on the trial.

After completion of study treatment, patients are followed up every 2 months for the first year, every 3 months for the second year, and every 4 months for the third year. After 3 years, clinical outcomes are monitored at least once a year until 5 years after treatment.

Conditions

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Glioblastoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
The MRI scan indicating progressive disease will be fused with our treatment planning scan and the region of progression will be contoured by an investigator blinded to the GTV\_MRI, T2\_FLAIR\_NCET, GTV\_PET, PTV\_high, and isodose lines.

Study Groups

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Arm A (short course RT)

Patients undergo short course RT for 5-10 fractions over 1-2 weeks on study. Patients also receive temozolomide PO on days 1-5 every 28 days during radiation therapy. Starting one month post-radiation, patients continue temozolomide on days 1-5 every 28 days for up to 5 adjuvant cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT with 18-F-DOPA administered IV prior to RT on study, and undergo MRI prior to RT and throughout the trial. Patients may optionally undergo blood sample collection during screening and on the trial.

Group Type EXPERIMENTAL

Accelerated Hypofractionated Radiation Therapy

Intervention Type RADIATION

Undergo short course RT

Computed Tomography

Intervention Type PROCEDURE

Undergo CT simulation

Fluorodopa F 18

Intervention Type DRUG

Given IV

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Questionnaire Administration

Intervention Type OTHER

Complete questionnaires

Temozolomide

Intervention Type DRUG

Given PO

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Arm B (standard course RT)

Patients undergo standard course RT for 15-30 fractions over 3-6 weeks on study. Patients also receive temozolomide PO QD concurrently with radiation therapy and for up to 6 adjuvant cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT with 18-F-DOPA administered IV prior to RT on study, and undergo MRI prior to RT and throughout the trial. Patients may optionally undergo blood sample collection during screening and on the trial.

Group Type ACTIVE_COMPARATOR

Computed Tomography

Intervention Type PROCEDURE

Undergo CT simulation

Fluorodopa F 18

Intervention Type DRUG

Given IV

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Questionnaire Administration

Intervention Type OTHER

Complete questionnaires

Radiation Therapy

Intervention Type RADIATION

Undergo standard course RT

Temozolomide

Intervention Type DRUG

Given PO

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Interventions

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Accelerated Hypofractionated Radiation Therapy

Undergo short course RT

Intervention Type RADIATION

Computed Tomography

Undergo CT simulation

Intervention Type PROCEDURE

Fluorodopa F 18

Given IV

Intervention Type DRUG

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Positron Emission Tomography

Undergo PET

Intervention Type PROCEDURE

Quality-of-Life Assessment

Ancillary studies

Intervention Type OTHER

Questionnaire Administration

Complete questionnaires

Intervention Type OTHER

Radiation Therapy

Undergo standard course RT

Intervention Type RADIATION

Temozolomide

Given PO

Intervention Type DRUG

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Other Intervention Names

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AHF-RT AHRT CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized Tomography CT CT Scan tomography (18F)FDOPA 18F-DOPA 18F-FDOPA 3-(2-Fluoro-(sup 18)F-4,5-dihydroxyphenyl)-L-alanine 6-(18F)Fluoro-L-DOPA Fluorine F 18 Fluorodopa Fluorine-18-fluoro-L-DOPA Fluorodopa (18F) FLUORODOPA F-18 L-6-(18F)Fluoro-DOPA Magnetic Resonance Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan NMR Imaging NMRI Nuclear Magnetic Resonance Imaging Medical Imaging, Positron Emission Tomography PET PET Scan Positron Emission Tomography Scan Positron-Emission Tomography PT Cancer Radiotherapy ENERGY_TYPE Irradiate Irradiated Irradiation Radiation Radiation Therapy, NOS Radiotherapeutics Radiotherapy RT Therapy, Radiation CCRG-81045 Gliotem Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo- M & B 39831 M and B 39831 Methazolastone RP-46161 SCH 52365 Temcad Temizole Temodal Temodar Temomedac TMZ Biological Sample Collection Biospecimen Collected Specimen Collection

Eligibility Criteria

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Inclusion Criteria

* Age \>= 18 years
* Histological and/or molecular confirmation of glioblastoma
* Eastern Oncology Group (ECOG) performance status (PS) =\< 3
* Ability to complete questionnaire(s) by themselves or with assistance
* Provide written informed consent or have a legally authorized representative (LAR) who is responsible for the care and well-being of the potential study participant, provide consent
* Willing to return to enrolling institution for follow-up either in-person or by video visit
* Postoperative/post-biopsy tumor plus surgical bed size =\< 6 cm in maximum diameter. This measurement includes both the enhancing region identified via T1 MRI with contrast, as well as the surgical cavity

Exclusion Criteria

* Unable to undergo MRI scans with contrast
* Unable to undergo an 18F-DOPA-PET scan (e.g., Parkinson's Disease, taking carbidopa/levodopa and/or less than 48 hours from discontinuance)
* Any of the following:

* Pregnant women
* Nursing women
* Men or women of childbearing potential who are unwilling to employ adequate contraception
* Tumors with IDH mutation
* Previous brain radiation therapy
* Patients who will not receive any radiation treatment or who will receive radiation treatment elsewhere (Note: radiotherapy can be given on the trial at Mayo Clinic facilities in Rochester, Arizona, or Florida, as well as at the Mayo Clinic Health System sites). Temozolomide, however, can be provided by another institution
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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William G. Breen, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic in Rochester

Roman O. Kowalchuk, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic in Rochester

Locations

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Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Site Status

Mayo Clinic in Florida

Jacksonville, Florida, United States

Site Status

Mayo Clinic Health System in Albert Lea

Albert Lea, Minnesota, United States

Site Status

Mayo Clinic Health Systems-Mankato

Mankato, Minnesota, United States

Site Status

Mayo Clinic Radiation Therapy - Northfield

Northfield, Minnesota, United States

Site Status

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

Mayo Clinic Health System-Eau Claire

Eau Claire, Wisconsin, United States

Site Status

Mayo Clinic Health System-Franciscan Healthcare

La Crosse, Wisconsin, United States

Site Status

Countries

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United States

Related Links

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Other Identifiers

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NCI-2023-01559

Identifier Type: REGISTRY

Identifier Source: secondary_id

GMROR2261

Identifier Type: OTHER

Identifier Source: secondary_id

22-006990

Identifier Type: OTHER

Identifier Source: secondary_id

GMROR2261

Identifier Type: -

Identifier Source: org_study_id

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