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A Randomized Phase III Trial of Memantine and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Patients With Brain Metastases
This randomized phase III trial compares memantine hydrochloride and whole-brain radiotherapy with or without hippocampal avoidance in reducing neurocognitive decline in patients with cancer that has spread from the primary site (place where it started) to the brain. Whole brain radiotherapy (WBRT) is the most common treatment for brain metastasis. Unfortunately, the majority of patients with brain metastases experience cognitive (such as learning and memory) deterioration after WBRT. Memantine hydrochloride may enhance cognitive function by binding to and inhibiting channels of receptors located in the central nervous system. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Using radiation techniques, such as intensity modulated radiotherapy to avoid the hippocampal region during WBRT, may reduce the radiation dose to the hippocampus and help limit the radiation-induced cognitive decline. It is not yet known whether giving memantine hydrochloride and WBRT with or without hippocampal avoidance works better in reducing neurocognitive decline in patients with brain metastases.
Details
| Lead sponsor | NRG Oncology |
|---|---|
| Phase | Phase 3 |
| Status | COMPLETED |
| Enrolment | 518 |
| Start date | 2015-07 |
| Completion | 2019-08-26 |
Conditions
- Cognitive Impairment
- Metastatic Malignant Neoplasm in the Brain
- Solid Neoplasm
Interventions
- Whole brain radiation therapy with hippocampal avoidance
- Memantine
- Whole brain radiation therapy
Primary outcomes
- Time to Neurocognitive Failure — From randomization to last follow-up. Maximum follow-up was 15.6 months.
Neurocognitive failure is defined as the first failure, defined as a neurocognitive decline using the reliable change index (RCI) on at least one of the following assessments or parts of : Hopkins Verbal Learning Test - Revised (HVLT-R), Trail Making Test (TMT), or Controlled Oral Word Association (COWA). The HVLT-R has 3 parts that were analyzed separately for decline: Total Recall, Delayed Recall, and Delayed Recognition. The TMT has 2 parts that were analyzed separately: Part A and Part B. Neurocognitive failure rate is estimated using the cumulative incidence method. Analysis was planned to occur after 233 events were reported. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Six-month rates are provided.Analysis was planned to occur after 233 events were reported.
Countries
United States, Canada