MEMCRT: Memantine to Prevent Thinking Problems in Children Receiving Radiation for Certain Brain Tumors

Brief Summary

Childhood brain tumor survivors treated with cranial radiation therapy are at significant risk for cognitive late effects of their disease and treatment that negatively impact quality of life. Children treated for localized brain tumors have a high survival rate, so improving quality of survivorship, including cognitive outcomes, is imperative.

The vascular hypothesis of radiation injury suggests that the mechanism of radiation-induced injury is similar to small vessel disease as seen with vascular dementia, prompting interest in treatments for vascular dementia. Randomized placebo-controlled clinical trials have shown memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, improves cognition in patients with mild to moderate vascular dementia without concerning side effects. Memantine during radiotherapy for brain metastases in adults has also been shown to be well tolerated with less cognitive decline over time, relative to placebo. Studies with children with attention deficit hyperactivity disorder (ADHD) or autism spectrum disorders have shown memantine is safe and improves cognition. There are no published studies of memantine in children undergoing treatment for brain tumors.

This clinical trial is supported by the National Institutes of Health and the National Cancer Institute.

Primary Objective

• To estimate the participation rate in a study of memantine used as a neuro-protective agent in children undergoing radiotherapy for localized brain tumors
• To estimate the rate of memantine medication adherence
• To estimate the rate of completion of cognitive assessments

Eligibility Criteria

Inclusion criteria include:

• Between 6 and 21 years old
• Diagnosis of localized low-grade glioma [e.g., pilocytic astrocytoma, optic pathway glioma, oligodendroglioma, ganglioglioma, pleomorphic xanthoastrocytoma (PXA)]; craniopharyngioma, ependymoma, meningioma or germ cell tumor
• Initiating focal cranial radiation therapy (photon or proton)
• Able to swallow pills
• Participant and parent/legal guardian speak, read and understand English
• Normal ECG and laboratory tests
• Adequate vision and hearing

Exclusion Criteria include:

• Prior cranial radiation therapy
• Pregnancy
• Medical disorder that would endanger participant’s well-being
• History of significant neurological disease, including poorly controlled seizures
• Psychiatric condition that would preclude or take precedence over study participation
• IQ below 70
• Treatment with psychotropic medication started within previous four weeks, unless prescribed specifically as an anti-emetic
• History of substance abuse
• Hypersensitivity or reaction to NMDA receptor antagonists

Study Sites

St. Jude Children’s Research Hospital
Memphis, Tennessee

About this study

Children with brain tumors who have had radiation therapy are at risk for problems with attention, memory and problem solving. These problems may cause difficulty in school and daily life. In this clinical trial, researchers want to find out if a drug called memantine can help prevent these kinds of problems in children and young adults with the following kinds of localized brain tumors: low-grade glioma, craniopharyngioma, ependymoma and germ cell tumors. This would be the first study of memantine in children with localized brain tumors.

Memantine has not been approved by the U.S. Food and Drug Administration (FDA) for use in children. However, earlier studies have shown it may improve memory for patients with dementia, attention deficit hyperactivity disorder (ADHD) and autism.  Scientists have also used this drug in adult cancer patients going through radiation therapy. They found patients had fewer thinking problems over time, compared to patients taking pills with no medicine in them (placebos). These studies have shown few side effects.

Purpose of this clinical trial

Researchers want to learn several things in this study. They want to find out how often families participate and how well patients take the medicine as prescribed. They also want to find out the side effects of the medicine and how often they may happen. Researchers also want to know if patients will complete the psychological testing for the study. In addition, they want to find out how neurological symptoms and thinking skills change when patients take memantine during radiation treatment for localized brain tumors.

Eligibility overview

• Between 6 and 21 years old
• Diagnosis of localized low-grade glioma, craniopharyngioma, ependymoma, meningioma  or germ cell tumor
• Initiating cranial radiation therapy (photon or proton)
• Able to swallow pills
• Participant and parent/legal guardian speak, read and understand English
• Normal ECG and laboratory tests
• Adequate vision and hearing