ACCL2031, A Phase 3 Randomized, Placebo-Controlled Trial Evaluating Memantine (IND# 149832) for Neurocognitive Protection in Children Undergoing Cranial Radiotherapy as Part of Treatment for Primary Central Nervous System Tumors

Protocol # :
Brain Neoplasm
Recurrent Brain Neoplasm
Disease Sites
Brain and Nervous System
Principal Investigator
Ullrich, Nicole

Trial Description

This phase III trial compares memantine to usual treatment in treating patients with brain
tumors that are newly diagnosed or have come back (recurrent). Memantine may block receptors
(parts of nerve cells) in the brain known to contribute to a decline in cognitive function.
Giving memantine may make a difference in cognitive function (attention, memory, or other
thought processes) in children and adolescents receiving brain radiation therapy to treat a
primary brain tumor.

Eligibility Requirements

Inclusion Criteria:

- >= 4 and < 18 years at time of study entry

- Patients must weigh 15 kg or greater at time of study entry

- Newly diagnosed or recurrent primary brain tumors that have not received prior cranial

- Planned focal, cranial or craniospinal radiation treatment for a primary brain tumor

- The patient must have receptive and expressive language skills in English, French or
Spanish since the neurocognitive function and quality of life (QOL) assessment
instruments are available in these languages only

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

- Age: 4 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 male; 0.8 female

- Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 male; 1 female

- Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 male; 1.2 female

- Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 male; 1.4 female

- Age: >= 16 years; Maximum serum creatinine (mg/dL): 1.7 male; 1.4 female

- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135

- Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L

- The patient must be able to undergo magnetic resonance imaging

- All patients and/or their parents or legal guardians must sign a written informed

- All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met

Exclusion Criteria:

- Life expectancy of less than 18 months

- Pre-existing conditions:

- Any contraindication or allergy to memantine

- Intractable seizures while on adequate anticonvulsant therapy, defined as more
than one seizure per month for the past 2 months or since initiating
anticonvulsant therapy

- Co-morbid systemic illnesses, psychiatric conditions, social situations, or other
severe concurrent disease which, in the judgment of the investigator, would make
the patient inappropriate for entry into this study or interfere significantly
with the proper assessment of safety and toxicity of the prescribed regimens or
would limit compliance with the study requirements

- Patients with a motor, visual, or auditory condition that precludes computerized
neurocognitive assessments are not eligible to participate

- Patients with any medical condition or taking medications that lead to
alterations of urine pH towards the alkaline condition (e.g., renal tubular
acidosis, carbonic anhydrase inhibitors, sodium bicarbonate)

- Personal history of prior cranial or craniospinal radiotherapy is not allowed

- Note: Prior anti-cancer therapy including surgery, chemotherapy, targeted agents
are allowed as per standard of care clinical treatment guidelines

- Female patients who are pregnant are excluded since fetal toxicities and teratogenic
effects have been noted for the study drug. A pregnancy test is required for female
patients of childbearing potential

- Lactating females who plan to breastfeed their infants

- Sexually active patients of reproductive potential who do not agree to use an
effective contraceptive method for the duration of their study participation