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

S
Sandeep Batra, MD

Primary Investigator

Enrolling By Invitation
4-17 years
All
Phase 3
3 Locations

Overview

What is the purpose of this study?
This phase III trial compares memantine to usual treatment in treating patients with primary central nervous system tumors. 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 central nervous system tumors.

Description

What will happen during the study?
Patients are randomized to 1 of 2 arms:
  1. ARM I: Patients receive memantine hydrochloride orally (PO) once daily (QD) for week 1 and then twice daily (BID) for weeks 2-24 in the absence of disease progression or unacceptable toxicity. Patients also complete cognitive testing over 20-30 minutes at baseline, end of radiation therapy, and at 3, 6, 12, 24, and 48 months. Patients undergo MRI and may optionally undergo blood sample collection throughout the trial.
  2. ARM II: Patients receive placebo PO QD for week 1 and then BID for weeks 2-24 in the absence of disease progression or unacceptable toxicity. Patients also complete cognitive testing over 20-30 minutes at baseline, end of radiation therapy, and at 3, 6, 12, 24, and 48 months. Patients undergo MRI and may optionally undergo blood sample collection throughout the trial.
THIS STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic.

Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632

Eligibility

You may be eligible for this study if you meet the following criteria:

  • Conditions:
    Central Nervous System Carcinoma, Brain Tumor, Riley
  • Age: Between 4 Years - 17 Years
  • Gender: All

Inclusion Criteria:

  •     >= 4 and < 18 years at time of study entry
  •     Patients must weigh 15 kg or greater at time of study entry
  •     Primary central nervous system tumors that have not received prior cranial radiotherapy
  •     Planned focal, cranial or craniospinal radiation treatment for a primary central nervous system 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 U/L
  •         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 consent
  •     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 study drug (memantine or placebo)
  •         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
  •         History of neurodevelopmental disorder such as Down syndrome, Fragile X, William's Syndrome, intellectual disability (presumed intelligence quotient [IQ] < 70), etc
  •         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 participation in computerized neurocognitive assessments
  •         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
  •  

Updated on 12 Sep 2024. Study ID: PHO-COG-ACCL2031, 14264, TX11470
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