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

Glioblastoma Clinical Trial

Official title:

Stereotactic Accelerated Radiotherapy in GlioblastomA (SAGA)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05781321
• Other study ID #: GMROR2261
• Secondary ID: NCI-2023-01559GM
• Status: Recruiting
• Phase: Phase 2
• Start date: March 23, 2023
• Est. completion date: March 2, 2028

Study information

• Verified date: March 2024
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 170
• Est. completion date: March 2, 2028
• Est. primary completion date: March 2, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glioblastoma

Intervention

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
• Positron Emission Tomography
Undergo PET

Other:
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Complete questionnaires

Radiation:
• Radiation Therapy
Undergo standard course RT

Drug:
• Temozolomide
Given PO

Procedure:
• Biospecimen Collection
Undergo blood sample collection

Locations

Country	Name	City	State
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients alive (overall survival [OS]) at 12 months	Comparisons between arms will be made by using a one-sided non-inferiority test of the difference in proportions with a non-inferiority limit of 10% and alpha level of .10. All patients meeting eligibility criteria who have signed a consent form, were randomized, and started treatment will be considered evaluable.	Up to 12 months after enrollment
Secondary	Proportion of patients whose physician reported a grade 3+ toxicity	Comparisons between arms will be made by using either the Chi-square or Fisher's Exact test for each time point. All patients meeting the eligibility criteria who signed a consent form and started treatment will be in the analysis.	Up to 30-, 90-, and 180-days post-radiotherapy (RT)
Secondary	Quality of life: Wilcoxon Rank-sum test	Changes over time from baseline will be compared between arms using the 2-sample t-test (or Wilcoxon Rank-Sum test for non-normal data). All patients meeting the eligibility criteria who have signed a consent form, started treatment, and have non-missing data on these questionnaires will be evaluable for these analyses. Changes will be measured from baseline over time of study.	From baseline up to 3 years
Secondary	Quality of life: EORTC QLQ-C30 (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire)	Changes over time from baseline will be compared between arms using the EORTC QLQ-C30 questionnaire. All patients meeting the eligibility criteria who have signed a consent form, started treatment, and have non-missing data on these questionnaires will be evaluable for these analyses. Score is caluclated from the mean of 13 of the 15 QLQ-C30 scales.	From baseline up to 3 years
Secondary	Quality of life: EORTC QLQ-BN20 Questionnaire	Changes over time from baseline will be compared between arms using the EORTC-BN20 questionnaire. All patients meeting the eligibility criteria who have signed a consent form, started treatment, and have non-missing data on these questionnaires will be evaluable for these analyses on a scale of 1-4, 1 being the lesser degree and 4 being the highest degree.	From baseline up to 3 years
Secondary	Lymphocyte count	Lymphocyte count at nadir will be compared between arms using the 2-sample t-test (or Wilcoxon Rank-Sum test for non-normal data). Additionally, the absolute change in lymphocyte count from pretreatment to end of RT will be compared between arms using an analysis of covariance (ANCOVA).	From baseline up to 3 years