Stereotactic Radiosurgery Compared With Hippocampal-Avoidant Whole Brain Radiation Therapy (HA-WBRT) Plus Memantine for 5-15 Brain Metastases

Official Title

A Phase III Trial of Stereotactic Radiosurgery Compared With Hippocampal-Avoidant Whole Brain Radiation Therapy (HA-WBRT) Plus Memantine for 5-15 Brain Metastases

Summary:

Stereotactic radiosurgery (SRS) is a commonly used treatment for brain tumours. It is a one-day (or in some cases two day), out-patient procedure during which a high dose of radiation is delivered to small spots in the brain while excluding the surrounding normal brain. Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) is when radiation therapy is given to the whole brain, while trying to decrease the amount of radiation that is delivered to the area of the hippocampus. The hippocampus is a brain structure that is important for memory. Memantine is a drug that is given to help relieve symptoms that can be caused by WBRT, including problems with memory and other mental symptoms. Health Canada, the regulatory body that oversees the use of drugs in Canada, has not approved the sale or use of memantine in combination with WBRT to treat this kind of cancer, although they have allowed its use in this study.

Trial Description

Primary Outcome:

• Overall Survival
• Neurocognitive progression-free survival

Secondary Outcome:

• Time to central nervous system (CNS) failure (local, distant, and leptomeningeal) in patients who receive SRS compared to patients who receive HA-WBRT + memantine
• Difference in CNS failure patterns (local, distant, or leptomeningeal) in patients who receive SRS compared to patients who receive HA-WBRT + memantine
• Number of salvage procedures following SRS in comparison to HA-WBRT + memantine
• Neurocognitive progression-free survival in patients who receive SRS compared to HA-WBRT + memantine
• Tabulate and descriptively compare the post-treatment adverse events associated with the interventions.
• Time delay to (re-)initiation of systemic therapy in patients receiving SRS in comparison to HA-WBRT + memantine
• Prospectively validate a predictive nomogram for distant brain failure in patients who receive SRS
• Compare the estimated cost of brain-related therapies in patients who receive SRS compared to patients who receive HA-WBRT + memantine.
• Quality of life, as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) with brain cancer module (BN20)
• Quality of life assessed by ECOG performance status
• Quality of life, as assessed by EQ-5D-5L
• Collect plasma to evaluate whether detectable somatic mutations in liquid biopsy can enhance prediction of the overall survival and development of new brain metastases.
• Analysis of serum samples for inflammatory biomarker C-reactive protein and brain-derived-neurotrophic factor (BDNF) to elucidate molecular/genomic mechanisms of neurocognitive decline and associated radiographic changes
• Collect whole-brain dosimetry in SRS patients to be prospectively correlated with cognitive toxicity, intracranial control and radiation necrosis
• Evaluate serial changes in imaging features found in routine MRI images (T2w changes, morphometry) that may predict tumour control and/or neurocognitive outcomes

The purpose of this research study is to compare the effects (good or bad) of receiving stereotactic radiosurgery (SRS) versus receiving hippocampal-avoidant whole brain radiation therapy (HA-WBRT) plus a drug called memantine, on brain metastases. Receiving SRS could control cancer that has spread to the brain. This study will allow the researchers to know whether this different approach is better, the same, or worse than the usual approach. To decide if it is better, the study doctors will be looking to see if the stereotactic radiosurgery (SRS) helps to either slow the growth of cancer or stop it from coming back, compared to the usual approach. Doctors will also look to see if this new approach increases the life span of patients with this type of cancer, and if it helps with quality of life and cancer related symptoms. The usual approach for patients who are not in a study is treatment with whole brain radiation therapy alone (WBRT).

View this trial on ClinicalTrials.gov