Stereotactic radiosurgery (SRS) is a commonly used treatment for brain tumors. 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.
Patients must have 5 or more brain metastases as counted on a T1 contrast enhanced MRI obtained ≤ 30 days from randomization (maximum 15 brain metastases).
Patients must have a pathological diagnosis (cytological or histological) of a non-hematopoietic malignancy.
The largest brain metastasis must measure <2.5 cm in maximal diameter.
Centre must have the ability to treat patients with either a Gamma Knife, Cyberknife, or a linear accelerator-based radiosurgery system.
Pregnant or nursing women.
Men or women of childbearing potential who are unwilling to employ adequate contraception.
Inability to complete a brain MRI.
Known allergy to gadolinium.
Parallel
Memantine
Drug20 mg (10 mg divided twice daily). Dose will be escalated by 5 mg per week. Memantine should start at 5 mg, and then increased in 5 mg increments at the following schedule, depending on the patient's response and tolerance:
Hippocampal-avoidant (HA-WBRT) Radiotherapy
Radiation30Gy in 10 fractions
Stereotactic Radiosurgery (SRS)
Procedure/Surgery18-20 or 22 Gy in single fraction
Overall Survival
To compare the overall survival in patients with five to fifteen brain metastases who receive SRS compared to patients who receive HA-WBRT + memantine
Neurocognitive progression-free survival
To compare the neurocognitive progression-free survival in patients with five to fifteen brain metastases who receive SRS compared to patients who receive HA-WBRT + memantine
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
measured from date the patient is randomized to date at which there is a drop of at least 1.5 standard deviations from baseline in two of the six neurocognitive tests (all tests are standardized based on published norms)
Click on the lead sponsor to view all of their trials.
Canadian Cancer Trials Group
Lead sponsor
Alliance for Clinical Trials in Oncology
Collaborator
NRG Oncology
Collaborator
