Comparing Single vs Multiple Doses of Radiation for Patients on Immunotherapy for Breast, Kidney, Small Cell Lung Cancer, Non-Small Cell Lung Cancer or Melanoma that Has Spread to the Brain, HYPOGRYPHE Study

Summary

Objectives

PRIMARY OBJECTIVE:
I. To compare the proportion of participants experiencing Grade 2 or higher Adverse Radiation Effects (ARE) within 9 months following randomization to single fraction stereotactic radiosurgery (SSRS) versus (vs) fractionated stereotactic radiosurgery (FSRS) in patients with brain metastases >= 2 cm in diameter or >= 4cc in volume treated with concurrent immune checkpoint inhibitor (ICI) therapy.

SECONDARY OBJECTIVES:
I. To compare the time to the composite endpoint of either local failure of a metastasis treated with stereotactic radiosurgery (SRS) or first Grade 2 or higher ARE between SSRS and FSRS groups.
II. To compare time to local failure between SSRS and FSRS groups.
III. To compare time to neurologic death between groups.
IV. To compare patient-reported brain tumor specific symptom burden using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) between SRSS or FSRS groups at 9 months.

EXPLORATORY OBJECTIVES:
I. To estimate time to first grade 2 or higher ARE, Central Nervous System (CNS) progression-free survival, and overall survival within groups.
II. To compare the proportion of patients requiring increasing or persistent use of steroids between SSRS and FSRS arms.
III. To compare neurocognitive outcomes between SRSS and FSRS groups at 2 and 9 months post-completion of SRS using the Rey Auditory Verbal Learning Test Revised (RAVLT), Controlled Oral Word Association (COWA) test, and the Trail Making Test (TMT) parts A and B.
IV. To compare cognition failure- or neurologic death-free survival (CFNDFS) between the SSRS and FSRS groups.
V. To compare patient-reported symptom burden using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) and a single item (item 5) from the Functional Assessment of Cancer Therapy—General Population (GP5) between SRSS or FSRS groups and over time.
VI. To compare time to significant decline in patient-reported symptom burden (decline in MDASI-BT > 0.5 standard deviation) between SRSS or FSRS groups.
VII. To assess differences in outcomes adjusted for: 1) histology subgroups of Renal Cell Carcinoma (RCC), Melanoma, Non-Small Cell Lung Cancer (NSCLC), Small Cell Lung Cancer (SCLC), or breast cancers, 2) type of systemic therapy (ICI monotherapy, dual immunotherapy, chemo-immunotherapy, targeted agent plus ICI), 3) timing of ICI delivery (before versus after SRS), 4) number of lesions, 5) presence of lesions in eloquent brain regions; and 6) presence of extracranial metastases.
VIII. To assess tumor microenvironment changes in patients that undergo a biopsy or resection.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo single fraction stereotactic radiosurgery on study. Patients undergo magnetic resonance imaging (MRI) throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study.

ARM II: Patients undergo fractionated stereotactic radiosurgery for up to 5 treatments over a few days. Patients undergo MRI throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study.

Patients are followed for 12 months after the completion of stereotactic radiosurgery.