This clinical trial aims to evaluate the efficacy of early intervention with Memantine and Pioglitazone in preventing Radiation-Induced Brain Injury (RIBI) in patients undergoing cranial radiotherapy. RIBI, a significant complication of radiation therapy for primary and metastatic brain tumors, as well as head and neck cancers, often presents with delayed and irreversible neurological damage, severely affecting patients' quality of life. Our previous studies have indicated that Memantine, an NMDAR antagonist, and Pioglitazone, a PPAR-γ agonist, play crucial roles in modulating the neuroprotective immune microenvironment by targeting key mechanisms of neuron-astrocyte fatty acid metabolism coupling. These findings suggest that early administration of these drugs could protect cognitive function and reduce neuroinflammation in patients post-radiation. This prospective phase II clinical trial will assess the combined efficacy of Memantine and Pioglitazone in improving cognitive outcomes and preventing RIBI without adversely impacting the anti-tumor efficacy of radiation therapy. The study will also explore the synergistic effects of these two FDA-approved drugs in early-stage RIBI prevention, providing a new therapeutic strategy for enhancing the quality of life in cancer patients receiving radiotherapy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
67
Oral administration of Memantine Tablets (10mg/tablet): Week 1: 5mg in the morning. Week 2: 5mg twice daily. Week 3: 10mg in the morning, 5mg in the evening. Weeks 4-24: 10mg twice daily.
Simultaneous oral administration of Pioglitazone Tablets (15mg/tablet): Weeks 1-24: 30mg once daily.
Based on the RTOG 0933 protocol, hippocampal and perihippocampal regions are delineated, and hippocampal dose constraints are applied. The radiation dose to the perihippocampal region is determined based on the size, number, and volume of brain metastases (whole-brain radiation therapy: DT 30Gy/10F, weeks 1-2; with a simultaneous boost to the pathological local area if necessary, 10-20Gy).
the cumulative incidence of cognitive failure
the proportion of participants who experience cognitive impairments after radiation therapy
Time frame: At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy
Cognitive Score Decline
based on the Reliable Change Index of at least one cognitive test
Time frame: At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy
Progressive-free survival for Intracranial Tumors
latencies to the first intracranial treatment failure or death from any cause
Time frame: At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy
Overall Survival
death due to any cause
Time frame: At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy
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