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.
Recursive Partitioning Analysis (RPA), Class I ~ Class II
Karnofsky Performance Status of ≥70
The primary tumor must be pathologically confirmed. For newly diagnosed brain metastases, the number of metastases is not limited, but the brain metastases could not have been within 5 mm of hippocampus. Additionally, there must be no hard or soft meningeal metastases.
No history of whole-brain radiation therapy; patients who are eligible for surgical resection of brain metastases prior to radiation therapy are allowed.
Radiographic evidence of hydrocephalus or other architectural distortion of the ventricular system, including placement of external ventricular drain or ventriculoperitoneal shunt.
Planned cytotoxic chemotherapy during the WBRT.
Pregnant or lactating women (Women of childbearing age must undergo a pregnancy test; effective contraception must be enforced during the treatment period).
Previous cranial radiation therapy (Except for patients with head and neck cancer where the disease site is outside the cranial radiation field).
Single group
Memantine Oral Tablet
DrugOral 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.
Pioglitazone 15mg
DrugSimultaneous oral administration of Pioglitazone Tablets (15mg/tablet): Weeks 1-24: 30mg once daily.
Hippocampal avoidance whole-brain radiotherapy (HA-WBRT)
RadiationBased 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
Cognitive Score Decline
based on the Reliable Change Index of at least one cognitive test
Progressive-free survival for Intracranial Tumors
latencies to the first intracranial treatment failure or death from any cause
Overall Survival
death due to any cause
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Affiliated Cancer Hospital & Institute of Guangzhou Medical University
Lead sponsor
Guangdong Provincial People's Hospital
Collaborator
Fujian Medical University Union Hospital
Collaborator
Southern Medical University, China
Collaborator
The Affiliated Panyu Center Hospital of Guangzhou Medical University
Collaborator
The Central Hospital of Shaoyang City
Collaborator
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