Clinical Trial Finder

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.

• - Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study) - 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 are excluded.

• - 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

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.#46;) 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.

Arms

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 throughout the trial. Patients may optionally undergo blood sample collection during screening and on the trial.

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 throughout the trial. Patients may optionally undergo blood sample collection during screening and on the trial.

Interventions

Radiation: - Accelerated Hypofractionated Radiation Therapy

Undergo short course RT

Procedure: - Computed Tomography

Undergo CT simulation

Drug: - Fluorodopa F 18

Given IV

Procedure: - Magnetic Resonance Imaging

Undergo MRI

Procedure: - Positron Emission Tomography

Undergo PET

Other: - Quality-of-Life Assessment

Ancillary studies

Other: - Questionnaire Administration

Complete questionnaires

Radiation: - Radiation Therapy

Undergo standard course RT

Drug: - Temozolomide

Given PO

Procedure: - Biospecimen Collection

Undergo blood sample collection