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

Phase 2

Recruiting

• Conditions: Glioblastoma
• Interventions: Radiation: Accelerated Hypofractionated Radiation Therapy; Procedure: Computed Tomography; Drug: Fluorodopa F 18; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Radiation Therapy; Drug: Temozolomide; Procedure: Biospecimen Collection

• Registration Number: NCT05781321
• Lead Sponsor: Mayo Clinic

Brief Summary

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

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 absolutely 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 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.

Study Timeline

• Study First Submitted: 2023-02-27
• Study First Submitted QC: 2023-03-19
• Study Start: 2023-03-23
• Study First Posted: 2023-03-23
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-23
• Last Update Posted: 2025-03-26
• Primary Completion: 2027-03-02
• Study Completion: 2028-03-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 170

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A (short course RT)	Accelerated Hypofractionated Radiation Therapy	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.
Arm A (short course RT)	Computed Tomography	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.
Arm A (short course RT)	Fluorodopa F 18	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.
Arm A (short course RT)	Magnetic Resonance Imaging	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.
Arm A (short course RT)	Positron Emission Tomography	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.
Arm A (short course RT)	Quality-of-Life Assessment	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.
Arm A (short course RT)	Questionnaire Administration	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.
Arm A (short course RT)	Temozolomide	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.
Arm A (short course RT)	Biospecimen Collection	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.
Arm B (standard course RT)	Computed Tomography	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.
Arm B (standard course RT)	Fluorodopa F 18	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.
Arm B (standard course RT)	Magnetic Resonance Imaging	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.
Arm B (standard course RT)	Positron Emission Tomography	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.
Arm B (standard course RT)	Quality-of-Life Assessment	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.
Arm B (standard course RT)	Questionnaire Administration	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.
Arm B (standard course RT)	Radiation Therapy	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.
Arm B (standard course RT)	Temozolomide	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.
Arm B (standard course RT)	Biospecimen Collection	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.

Primary Outcome Measures

Name	Time	Method
Proportion of patients alive [overall survival (OS)] at 12 months	Up to 12 months after enrollment	OS is defined as the time from study registration to death due to any cause.

Secondary Outcome Measures

Name	Time	Method
Proportion of patients whose radiation oncologist reported a grade 3+ toxicity	30-, 90-, and 180-days post-radiotherapy (RT)	Pretreatment symptoms/conditions will be graded at enrollment by the radiation oncology team and updated at each evaluation. Adverse Events will be calculated using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Quality of life: EORTC QLQ-C30	From baseline up to 3 years	Assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), a 30 item questionnaire used to assess quality of life in cancer patients. Questions are answered using a 4-point Likert scale where 1=not at all and 4=very much, except for two items which use a 7-point scale where 1=very poor and 7=excellent. Higher scores on the questions answered 1-4 indicate more severe symptoms and greater difficulty. Higher scores on the 1-7 scales indicate better overall health and quality of life.
Quality of life: EORTC QLQ-BN20	From baseline up to 3 years	Assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Brain Neoplasm (QLQ-BN20), which consists of 20 questions answered using a 4-point Likert scale where 1=not at all and 4=very much. Higher scores reflect more severe symptoms.
Lymphocyte count	From baseline up to 3 years	Assessed by blood test, lymphocyte count will be compared between arms by change in count from pretreatment to end of RT.

Trial Locations

Locations (8)

Mayo Clinic in Arizona; 🇺🇸 Scottsdale, Arizona, United States

Mayo Clinic in Florida; 🇺🇸 Jacksonville, Florida, United States

Mayo Clinic Health System in Albert Lea; 🇺🇸 Albert Lea, Minnesota, United States

Mayo Clinic Health Systems-Mankato; 🇺🇸 Mankato, Minnesota, United States

Mayo Clinic Radiation Therapy - Northfield; 🇺🇸 Northfield, Minnesota, United States

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States

Mayo Clinic Health System-Eau Claire; 🇺🇸 Eau Claire, Wisconsin, United States

Mayo Clinic Health System-Franciscan Healthcare; 🇺🇸 La Crosse, Wisconsin, United States