Advanced Imaging-Guided Standard Versus Dose-Intensified Radiation Therapy for the Treatment of Newly Diagnosed Glioblastoma, SAGA 2.0 Trial
Stereotactic Advanced-Imaging Guided Radiotherapy for Glioblastoma (SAGA 2.0)
This clinical trial studies how well advanced imaging-guided standard dose versus (vs.) dose-intensified radiation therapy (RT) and dose-intensified accelerated RT works in treating patients with newly diagnosed glioblastoma. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. During dose-intensified RT, a higher dose than normal of radiation therapy is delivered over 6 weeks. During dose-intensified accelerated RT, the higher dose of radiation therapy is delivered over a shorter amount of time (2 weeks) than normal (6 weeks). Patients also undergo an advanced brain imaging positron emission tomography (PET)/computed tomography (CT) scan (using a radioactive drug called either FET or FDOPA) prior to RT to that may help doctors better plan the treatment. Dose-intensified and dose-intensified accelerated radiation therapy may be effective in treating patients with newly diagnosed glioblastoma. Giving dose-intensified RT or dose-intensified accelerated RT guided by advanced imaging may work better than standard dose RT in treating patients with newly diagnosed glioblastoma.
IND Numbers: 61300, 140882, 176402, 154793, 167879
Study Overview
Status
Conditions
Intervention / Treatment
- Procedure: Biospecimen Collection
- Procedure: Magnetic Resonance Imaging
- Other: Questionnaire Administration
- Procedure: Computed Tomography
- Radiation: F-18 Fluoroethyltyrosine
- Drug: Fluorodopa F 18
- Radiation: Dose-intensified Photon Beam Radiation Therapy
- Procedure: Positron Emission Tomography
- Radiation: Proton Beam Radiation Therapy
- Radiation: Proton Beam Radiation Therapy
- Radiation: Proton Beam Radiation Therapy
- Radiation: Proton Beam Radiation Therapy
- Drug: Temozolomide
- Radiation: Standard Photon Beam Radiation Therapy
- Radiation: Dose-intensified Accelerated Photon Beam Radiation Therapy
- Radiation: Accelerated Photon Beam Radiation Therapy
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Arizona
-
Scottsdale, Arizona, United States, 85259
- Mayo Clinic in Arizona
-
Principal Investigator:
- Sujay A. Vora
-
Contact:
- Sujay A. Vora
- Phone Number: 480-342-2000
- Email: vora.sujay@mayo.edu
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-
Florida
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Jacksonville, Florida, United States, 32224-9980
- Mayo Clinic in Florida
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Principal Investigator:
- Daniel Trifiletti
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Contact:
- Daniel Trifiletti
- Phone Number: 904-953-2000
- Email: trifiletti.daniel@mayo.edu
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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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Contact:
- John E. Yeakel
- Phone Number: 507-668-2063
- Email: yeakel.john@mayo.edu
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Principal Investigator:
- John E. Yeakel
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Mankato, Minnesota, United States, 56001
- Mayo Clinic Health Systems-Mankato
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Contact:
- Jason T. Hayes
- Phone Number: 507-668-2063
- Email: hayes.jason@mayo.edu
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Principal Investigator:
- Jason T. Hayes
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Rochester, Minnesota, United States, 55905
- Mayo Clinic in Rochester
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Contact:
- William Breen
- Phone Number: 507-284-3261
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Principal Investigator:
- William Breen
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Wisconsin
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Eau Claire, Wisconsin, United States, 54701
- Mayo Clinic Health System-Eau Claire Clinic
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Contact:
- Now Bahar Alam
- Phone Number: 715-464-8124
- Email: alam.nowbahar@mayo.edu
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Principal Investigator:
- Now Bahar Alam
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La Crosse, Wisconsin, United States, 54601
- Mayo Clinic Health System-Franciscan Healthcare
-
Contact:
- Abigail L. Stockham
- Phone Number: 608-392-7332
- Email: stockham.abigail@mayo.edu
-
Principal Investigator:
- Abigail L. Stockham
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥ 18 years
- Histological confirmation of glioblastoma (IDH-wildtype)
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 3 at baseline
- 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 in accordance with ethical, regulatory, and institutional requirements
- Willing to return to enrolling institution for follow-up either in-person or by video visit (where indicated)
Exclusion Criteria:
- Known to be pregnant or nursing
- Unable to undergo MRI scans with contrast (such as patients with devices or metal in head that is MRI incompatible)
- Unable to undergo amino acid PET (FET or FDOPA) scan (such as allergy to the contrast/tracer, or technical or patient factors per the discretion of the treating physician)
- Prior radiation (including tile-based brachytherapy) or chemotherapy for glioblastoma (note: prior cancer diagnoses and treatment for other cancers are not exclusion criteria, and multiple surgeries prior to enrollment is not an exclusion criteria)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Arm A (dose-intensified radiation therapy)
Patients undergo thirty treatment fractions of dose-intensified proton or photon radiation therapy QD (Monday-Friday) over 6 weeks in the absence of disease progression or unacceptable toxicity. Patients may also receive SOC temozolomide during and/or after radiation therapy at the discretion of the treating team. Additionally, patients receive FET via injection or FDOPA IV and undergo PET/CT prior to treatment and optionally during treatment and follow-up. Patients also undergo MRI and blood sample collection throughout the study. |
Undergo blood sample collection
Other Names:
Undergo MRI
Other Names:
Ancillary studies Undergo FET or FDOPA PET/CT
Other Names:
Given via injection
Other Names:
Given IV
Other Names:
Undergo dose-intensified photon radiation therapy
Other Names:
Undergo FET or FDOPA PET/CT
Other Names:
Undergo dose-intensified proton radiation therapy
Other Names:
Undergo standard proton radiation therapy
Other Names:
Undergo dose-intensified accelerated proton radiation therapy
Other Names:
Undergo accelerated proton radiation therapy
Other Names:
Given SOC temozolomide
Other Names:
|
|
Active Comparator: Arm B (standard radiation therapy)
Patients undergo thirty treatment fractions of standard proton or photon radiation therapy QD (Monday-Friday) over 6 weeks in the absence of disease progression or unacceptable toxicity. Patients may also receive SOC temozolomide during and/or after radiation therapy at the discretion of the treating team. Additionally, patients receive FET via injection or FDOPA IV and undergo PET/CT prior to treatment and optionally during treatment and follow-up. Patients also undergo MRI and blood sample collection throughout the study. |
Undergo blood sample collection
Other Names:
Undergo MRI
Other Names:
Ancillary studies Undergo FET or FDOPA PET/CT
Other Names:
Given via injection
Other Names:
Given IV
Other Names:
Undergo FET or FDOPA PET/CT
Other Names:
Undergo dose-intensified proton radiation therapy
Other Names:
Undergo standard proton radiation therapy
Other Names:
Undergo dose-intensified accelerated proton radiation therapy
Other Names:
Undergo accelerated proton radiation therapy
Other Names:
Given SOC temozolomide
Other Names:
Undergo standard photon radiation therapy
Other Names:
|
|
Experimental: Arm C (dose-intensified accelerated radiation therapy)
Patients undergo ten treatment fractions of dose-intensified accelerated proton or photon radiation therapy QD (Monday-Friday) over 2 weeks in the absence of disease progression or unacceptable toxicity. Patients may also receive SOC temozolomide during and/or after radiation therapy at the discretion of the treating team. Additionally, patients receive FET via injection or FDOPA IV and undergo PET/CT prior to treatment and optionally during treatment and follow-up. Patients also undergo MRI throughout the study. |
Undergo MRI
Other Names:
Undergo FET or FDOPA PET/CT
Other Names:
Given via injection
Other Names:
Given IV
Other Names:
Undergo FET or FDOPA PET/CT
Other Names:
Undergo dose-intensified proton radiation therapy
Other Names:
Undergo standard proton radiation therapy
Other Names:
Undergo dose-intensified accelerated proton radiation therapy
Other Names:
Undergo accelerated proton radiation therapy
Other Names:
Given SOC temozolomide
Other Names:
Undergo dose-intensified accelerated photon radiation therapy
Other Names:
|
|
Active Comparator: Arm D (accelerated radiation therapy)
Patients undergo ten treatment fractions of accelerated proton or photon radiation therapy QD (Monday-Friday) over 2 weeks in the absence of unacceptable toxicity. Patients may also receive SOC temozolomide during and/or after radiation therapy at the discretion of the treating team. Additionally, patients receive FET via injection or FDOPA IV and undergo PET/CT prior to treatment and optionally during treatment and follow-up. Patients also undergo MRI throughout the study. |
Undergo MRI
Other Names:
Undergo FET or FDOPA PET/CT
Other Names:
Given via injection
Other Names:
Given IV
Other Names:
Undergo FET or FDOPA PET/CT
Other Names:
Undergo dose-intensified proton radiation therapy
Other Names:
Undergo standard proton radiation therapy
Other Names:
Undergo dose-intensified accelerated proton radiation therapy
Other Names:
Undergo accelerated proton radiation therapy
Other Names:
Given SOC temozolomide
Other Names:
Undergo accelerated photon radiation therapy
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Overall survival (Cohort 1)
Time Frame: Up to 18 months
|
Overall survival (OS) is defined as the time from registration until death due to any cause. Will be summarized by treatment arm using the difference in proportions test. |
Up to 18 months
|
|
Overall survival (Cohort 2)
Time Frame: Up to 12 months
|
Overall survival (OS) is defined as the time from registration until death due to any cause. A Bayesian pick-the-winner design will be used to identify the more promising treatment arm based on 12-month overall survival. |
Up to 12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Incidence of grade 3+ central nervous system (CNS) toxicity, regardless of attribution (Overall CNS toxicity)
Time Frame: Up to 36 months post-radiation therapy (RT)
|
CNS toxicities will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0. For each treatment arm, CNS toxicity will be summarized as: the number and proportion of patients experiencing at least one qualifying grade ≥ 3 CNS toxicity event. Between-arm comparisons will be performed descriptively. |
Up to 36 months post-radiation therapy (RT)
|
|
Incidence of grade 3+ higher CNS toxicity at least possibly attributable to radiation therapy (Treatment-related CNS toxicity)
Time Frame: Up to 36 months post-RT
|
As assessed by the treating investigator. CNS toxicities will be graded according to CTCAE 5.0. Events classified as possibly, probably, or definitely related to radiation therapy will be included. For each treatment arm, CNS toxicity will be summarized as: the number and proportion of patients experiencing at least one qualifying grade ≥ 3 CNS toxicity event. |
Up to 36 months post-RT
|
|
Quality of life (Cohort 1) - EORTC QLQ-C30
Time Frame: Up to 6 months post-RT
|
The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 is a 30-item questionnaire a questionnaire used to assess the quality of life of cancer patients. Twenty-eight questions are answered on a scale of 1-4 (1=not at all, 2=a little, 3=quite a bit, and 4= very much), and two questions are answered on a scale of 1-7 (1= very poor and 7=excellent). Higher summary scores indicate better health related quality of life. |
Up to 6 months post-RT
|
|
Quality of life (Cohort 1) - EORTC QLQ-BN20
Time Frame: Up to 6 months post-RT
|
The EORTC QLQ-BN20 is a 20-item questionnaire related to symptoms experienced by patients with brain cancer during the past week. Questions are answered on a scale of 1-4 where 1=not at all, 2=a little; 3-quite a bit; and 4=very much. Higher scores indicate greater severity of symptoms. |
Up to 6 months post-RT
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Neurocognitive outcomes (Cohort 1)
Time Frame: Up to 1 month post-RT
|
As measured by Mayo Test Drive (MTD), a web-based platform for remote self-administered cognitive assessment. The primary comparison will be the between-arm difference in mean change over time (arm-by-time interaction). Higher or average composite scores indicate functioning consistent with healthy cognitive peers for participant's age, sex, and education. Significantly negative scores suggest performance drops in memory and processing. An MTD score is a screening and monitoring tool, not a medical diagnosis. Lower scores do not automatically indicate Alzheimer's or dementia; they can be influenced by other factors such as fatigue, high stress, medications, technical issues during the test, or mild age-related changes. |
Up to 1 month post-RT
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: William Breen, Mayo Clinic in Rochester
Study record dates
Study Major Dates
Study Start (Estimated)
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
- Inorganic Chemicals
- Elements
- Chemistry Techniques, Analytical
- Spectrum Analysis
- Ions
- Electrolytes
- Electromagnetic Phenomena
- Magnetic Phenomena
- Radiotherapy
- Electromagnetic Radiation
- Gases
- Elementary Particles
- Light
- Optical Phenomena
- Radiation, Nonionizing
- Heavy Ion Radiotherapy
- Cations, Monovalent
- Cations
- Hydrogen
- Nucleons
- Temozolomide
- Radiation
- Specimen Handling
- Magnetic Resonance Spectroscopy
- Photons
- fluorodopa F 18
- Proton Therapy
- Protons
- (18F)fluoroethyltyrosine
Other Study ID Numbers
- GMROR2661
- NCI-2026-07628 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- 26-003443 (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
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