Hippocampal Avoidance in Craniospinal Irradiation for the Treatment of Leptomeningeal Metastases From Breast Cancer or Non-small Cell Lung Cancer
NCT Number: NCT06518057
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Anatomic Stage IV Breast Cancer AJCC v8|Metastatic Breast Carcinoma|Metastatic Lung Non-Small Cell Carcinoma|Metastatic Malignant Neoplasm in the Leptomeninges|Stage IV Lung Cancer AJCC v8
Interventions: PROCEDURE: Biospecimen Collection|PROCEDURE: Computed Tomography|OTHER: Electronic Health Record Review|PROCEDURE: Lumbar Puncture|PROCEDURE: Magnetic Resonance Imaging|PROCEDURE: Positron Emission Tomography|RADIATION: Proton Beam Craniospinal Irradiation|OTHER: Survey Administration|RADIATION: Volume Modulated Arc Therapy
Sponsor: University of Washington
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 22
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-12-01
Completion Date: 2027-06-30
Locations: Fred Hutch/University of Washington Cancer Consortium, Seattle, Washington, 98109, United States

Summary:
This phase II clinical trial studies how well craniospinal irradiation (CSI) with hippocampal avoidance, using proton therapy or volumetric modulated arc therapy (VMAT), works in treating patients with breast cancer or non-small cell lung cancer (NSCLC) that has spread from the original (primary) tumor to the cerebrospinal fluid (CSF) and meninges (thin layers of tissue that cover and protect the brain and spinal cord) (leptomeningeal metastases). Radiation therapy is an effective treatment in relieving localized symptoms caused by leptomeningeal metastases. However, the type of radiation therapy typically used does not prevent the spread of leptomeningeal disease. CSI (radiation therapy directed at the brain and spinal cord to kill tumor cells) may be able to target all of the areas of possible leptomeningeal tumor spread. CSI may however result in significant neurological side effects due to radiation damage to a part of the brain called the hippocampus. Hippocampal avoidance (HA) reduces the amount of radiation to the hippocampus. Proton or VMAT CSI with HA may be an effective treatment while reducing neurological side effects for patients with leptomeningeal metastases from breast cancer and NSCLC.

Primary Outcome Measures: Central nervous system (CNS)-progression free survival (PFS), PFS is defined as time from craniospinal irradiation (CSI) to CNS disease progression or death. CNS-PFS will be summarized using Kaplan-Meier methodology. Median, 95% confidence interval (CI) and Kaplan-Meier plot will be provided. One-sample log-rank test will be used to test if the median CNS PFS of hippocampal avoidance in CSI for leptomeningeal metastases from breast cancer or non-small cell lung cancer (NSCLC) is significantly larger than the expected median CNS PFS with involved-field radiation therapy (IFRT), i.e., 2.5 months. P-value will be provided., Up to 12 months
Secondary Outcome Measures: Number of adverse events associated with hippocampal avoidance craniospinal irradiation (HA-CSI), The analyses of the adverse events associated with HA-CSI will be descriptive in nature. Summary tables and listings will be provided for all reported adverse events (AEs)., Up to 12 months|Neurocognitive function assessment, Linear mixed models will be used to examine changes in neurocognitive domain (attention, executive functions, memory) performances from pre-RT baseline to 3, 6, and 12 months. Magnitude of change will be examined at each timepoint using standardized effect sizes (e.g., Cohen's d). For each timepoint, the study investigators will examine the proportion of individuals who demonstrate a reliable change in at least 2 (out of 10) test performances as compared to pre-RT baseline performances., Up to 12 months|Overall survival (OS), Comparison of OS between the study group and the historical cohort will be analyzed using stratified log-rank test. OS will be estimated and visualized using Kaplan-Meier methods., Up to 12 months