Short Course Radiotherapy for the Treatment of Patients With Glioblastoma, SAGA Study
Stereotactic Accelerated Radiotherapy in GlioblastomA (SAGA)
Study Overview
Status
Conditions
Intervention / Treatment
- Other: Quality-of-Life Assessment
- Procedure: Magnetic Resonance Imaging
- Procedure: Biospecimen Collection
- Procedure: Positron Emission Tomography
- Other: Questionnaire Administration
- Drug: Temozolomide
- Drug: Fluorodopa F 18
- Procedure: Computed Tomography
- Radiation: Accelerated Hypofractionated Radiation Therapy
- Radiation: Radiation Therapy
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 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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Arizona
-
Scottsdale, Arizona, United States, 85259
- Mayo Clinic in Arizona
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-
Florida
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Jacksonville, Florida, United States, 32224-9980
- Mayo Clinic in Florida
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Minnesota
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Albert Lea, Minnesota, United States, 56007
- Mayo Clinic Health System in Albert Lea
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Mankato, Minnesota, United States, 56001
- Mayo Clinic Health Systems-Mankato
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Northfield, Minnesota, United States, 55057
- Mayo Clinic Radiation Therapy - Northfield
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Rochester, Minnesota, United States, 55905
- Mayo Clinic in Rochester
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Wisconsin
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Eau Claire, Wisconsin, United States, 54701
- Mayo Clinic Health System-Eau Claire
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La Crosse, Wisconsin, United States, 54601
- Mayo Clinic Health System-Franciscan Healthcare
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: 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.
|
Ancillary studies
Other Names:
Undergo MRI
Other Names:
Undergo blood sample collection
Other Names:
Undergo PET
Other Names:
Complete questionnaires
Given PO
Other Names:
Given IV
Other Names:
Undergo CT simulation
Other Names:
Undergo short course RT
Other Names:
|
|
Active Comparator: 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.
|
Ancillary studies
Other Names:
Undergo MRI
Other Names:
Undergo blood sample collection
Other Names:
Undergo PET
Other Names:
Complete questionnaires
Given PO
Other Names:
Given IV
Other Names:
Undergo CT simulation
Other Names:
Undergo standard course RT
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Proportion of patients alive [overall survival (OS)] at 12 months
Time Frame: Up to 12 months after enrollment
|
OS is defined as the time from study registration to death due to any cause.
|
Up to 12 months after enrollment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Lymphocyte count
Time Frame: 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.
|
From baseline up to 3 years
|
|
Quality of life: EORTC QLQ-C30
Time Frame: 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.
|
From baseline up to 3 years
|
|
Quality of life: EORTC QLQ-BN20
Time Frame: 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.
|
From baseline up to 3 years
|
|
Proportion of patients whose radiation oncologist reported a grade 3+ toxicity
Time Frame: 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.
|
30-, 90-, and 180-days post-radiotherapy (RT)
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: William G. Breen, MD, Mayo Clinic in Rochester
- Principal Investigator: Roman O. Kowalchuk, MD, Mayo Clinic in Rochester
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Neoplasms by Histologic Type
- Neoplasms, Glandular and Epithelial
- Astrocytoma
- Glioma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Glioblastoma
- Organic Chemicals
- Heterocyclic Compounds, 1-Ring
- Heterocyclic Compounds
- Investigative Techniques
- Therapeutics
- Clinical Laboratory Techniques
- Diagnostic Techniques and Procedures
- Diagnosis
- Azoles
- Physical Phenomena
- Dacarbazine
- Triazenes
- Imidazoles
- Chemistry Techniques, Analytical
- Spectrum Analysis
- Temozolomide
- Radiotherapy
- Radiation
- Specimen Handling
- Magnetic Resonance Spectroscopy
- fluorodopa F 18
Other Study ID Numbers
- GMROR2261 (Other Identifier: Mayo Clinic Radiation Oncology)
- NCI-2023-01559 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- 22-006990 (Other Identifier: Mayo Clinic Institutional Review Board)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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