NCT04801342

Neurocognitive Outcome of Bilateral or Unilateral Hippocampal Avoidance WBRT With Memantine for Brain Metastases

Neurocognitive Outcome of Conformal Whole Brain Radiotherapy With Bilateral or Unilateral Hippocampal Avoidance Plus Memantine for Brain Metastases: A Phase II Single Blind Randomized Trial

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 72 (estimated)
• Sponsor: National Taiwan University Hospital · Academic / Other
• Sex: All
• Age: 20 Years
• Healthy volunteers: Not accepted

Summary

Brain metastases are the most common brain tumors in adults. It is estimated that around 10-30% of cancer patients would develop brain metastases during the course of their illness. Whole brain radiotherapy (WBRT) is the treatment of choice for the majority of patients with brain metastases. WBRT yields high radiologic response rate (27\~56%) and is effective in rapid palliation of neurologic symptoms as well as prolongs time to neurocognitive function decline caused by intracranial lesions. By using conventional fractionation, more than one- third of patients developed late neurocognitive toxicity while memory impairment was the most common symptom. The incidence is even higher when a formal and sensitive neurocognitive assessment was prospectively evaluated. With more long-term survivors nowadays, it has become increasingly important to minimize neurocognitive function decline and maintain quality of life in patients with brain metastasis. The function of hippocampus is cooperation in learning, consolidation and retrieval of information and essential for formation of new memories. Bilateral and unilateral radiation injury of the hippocampus is known to alter learning and memory formation. Several preclinical studies support the hypothesis of hippocampus-mediated cognitive dysfunction by ionizing radiation. Clinical studies show increase in radiation dose to hippocampus is associated with subsequent neurocognitive function impairment in adult and pediatric patients. Furthermore, the result of phase III randomized trials suggested hippocampal avoidance plus Memantine significantly reduce the risk of neurocognitive impairment at 6 months from 68.2% in control arm with standard WBRT to 59.5% in experimental arm. In the investigator's prior investigation, patients received conformal WBRT with bilateral hippocampal avoidance also had significant less declines in verbal memory at 6 months. Previous studies showed the right and left hippocampus exert different neurocognitive functions. Several retrospective studies also demonstrated that the radiation dose to the left hippocampus is more related to neurocognitive impairment. Planning study and investigation showed that by avoiding the left hippocampus alone, the radiation dose to the spared unilateral hippocampus is further decreased. In present study, a single blind randomized phase II trial is designed to investigate the effectiveness of neurocognitive function preservation using conformal WBRT with bilateral or unilateral hippocampal avoidance and memantine.

Conditions

• Metastatic Malignant Neoplasm to Brain

Interventions

Type	Name	Description
RADIATION	Conformal Whole Brain Radiotherapy with Unilateral Hippocampal Avoidance	Conformal Whole Brain Radiotherapy 30 Gy in 10 fractions with Unilateral Hippocampal Avoidance using Intensity modulated radiotherapy, Volumetric arc therapy, or Tomotherapy
RADIATION	Conformal Whole Brain Radiotherapy with Bilateral Hippocampal Avoidance	Conformal Whole Brain Radiotherapy 30 Gy in 10 fractions with Bilateral Hippocampal Avoidance using Intensity modulated radiotherapy, Volumetric arc therapy, or Tomotherapy
DRUG	Memantine Hydrochloride	Start from day 1 of WBRT orally for 24 weeks and escalating doses over the first 4 weeks

Timeline

• Start date: 2021-04-01
• Primary completion: 2024-01-01
• Completion: 2025-02-28
• First posted: 2021-03-17
• Last updated: 2021-03-17

Locations

1 site across 1 country: Taiwan

Regulatory

• FDA-regulated drug study
• FDA-regulated device study