A Phase 3 Randomized, Placebo-Controlled Trial Evaluating Memantine for Neurocognitive Protection in Children Undergoing Cranial Radiotherapy as Part of Treatment for Primary Central Nervous System Tumors
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 162
- 试验地点
- 276
- 主要终点
- The mean slope of the Cogstate composite Z score (an average of detection, Identification, and one-back Z scores, each Z score calculated using Cogstate age-based normative data)
研究概览
简要总结
This phase III trial compares memantine to placebo 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.
详细描述
PRIMARY OBJECTIVE:
I. To determine the efficacy, as measured by the slope of change of the Cogstate composite Z score from baseline to 12 months, of oral memantine hydrochloride (memantine) administered for a period of 6 months, when compared to placebo, in children ages 4-18 receiving cranial or craniospinal radiotherapy for primary central nervous system tumors.
EXPLORATORY OBJECTIVES:
I. To determine if memantine is associated with improved cognitive function as measured for participants in the optional Children's Oncology Group (COG) Standardized Battery at 12 months.
II. To determine if memantine is associated with change in cognitive function versus (vs.) placebo as measured by Cogstate composite score at end of radiation therapy (RT), 3 and 6 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 4 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •>= 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/sex 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
排除标准
- •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
研究组 & 干预措施
Arm I (memantine hydrochloride)
Patients receive memantine hydrochloride orally 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.
干预措施: Memantine Hydrochloride (Drug)
Arm I (memantine hydrochloride)
Patients receive memantine hydrochloride orally 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.
干预措施: Cognitive Assessment (Procedure)
Arm I (memantine hydrochloride)
Patients receive memantine hydrochloride orally 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.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm I (memantine hydrochloride)
Patients receive memantine hydrochloride orally 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.
干预措施: Questionnaire Administration (Other)
Arm II (placebo)
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.
干预措施: Biospecimen Collection (Procedure)
Arm II (placebo)
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.
干预措施: Cognitive Assessment (Procedure)
Arm II (placebo)
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.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm II (placebo)
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.
干预措施: Placebo Administration (Drug)
Arm II (placebo)
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.
干预措施: Questionnaire Administration (Other)
Arm I (memantine hydrochloride)
Patients receive memantine hydrochloride orally 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.
干预措施: Biospecimen Collection (Procedure)
结局指标
主要结局
The mean slope of the Cogstate composite Z score (an average of detection, Identification, and one-back Z scores, each Z score calculated using Cogstate age-based normative data)
时间窗: Up-to 12 months post baseline
Estimate the difference in mean Cogstate composite Z score slopes (reflecting change in Cogstate composite Z scores from baseline to 12 months post baseline taking into account measurements at those time points as well as end of radiation therapy and 3 and 6-months post baseline) between the treatment and control arms using a generalized estimating equation model with compound symmetry correlation structure. Will provide a point estimate and corresponding 95% confidence interval.
次要结局
未报告次要终点