Memantine Hydrochloride and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Reducing Neurocognitive Decline in Patients With Brain Metastases

Completed · Phase 3

Conditions studied: Cognitive Impairment, Metastatic Malignant Neoplasm in the Brain, Solid Neoplasm

In brief

This randomized phase III trial compares memantine hydrochloride and whole-brain radiotherapy with or without hippocampal avoidance in reducing neurocognitive decline in patients with cancer that has spread from the primary site (place where it started) to the brain. Whole brain radiotherapy (WBRT) is the most common treatment for brain metastasis. Unfortunately, the majority of patients with brain metastases experience cognitive (such as learning and memory) deterioration after WBRT. Memantine hydrochloride may enhance cognitive function by binding to and inhibiting channels of receptors located in the central nervous system. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Using radiation techniques, such as intensity modulated radiotherapy to avoid the hippocampal region during WBRT, may reduce the radiation dose to the hippocampus and help limit the radiation-induced cognitive decline. It is not yet known whether giving memantine hydrochloride and WBRT with or without hippocampal avoidance works better in reducing neurocognitive decline in patients with brain metastases.

Key facts

Study ID

NCT02360215

Run by

NRG Oncology

People needed

518

Starts

2015-07-01

Expected to finish

2019-08-26

Last updated by the study team

2025-04-23

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• PRIOR TO STEP 1 REGISTRATION:
• Brain metastases outside a 5-mm margin around either hippocampus must be visible on contrast-enhanced magnetic resonance imaging (MRI) performed =< 21 days prior to Step 1 registration; an allowed exception, regarding ability to image brain metastases, would be that patients who had undergone radiosurgery or surgical resection and are planning adjuvant WBRT do not have to have visible disease but do need a pre-surgery MRI or computed tomography (CT) scan demonstrating brain metastases; however, the brain metastases could not have been within 5 mm of either hippocampus
• Patients must have a gadolinium contrast-enhanced three-dimensional spoiled gradient (SPGR), magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) axial MRI scan with standard axial and coronal gadolinium contrast-enhanced T1-weighted sequence and axial T2/FLAIR sequence acquisitions; to yield acceptable image quality, the gadolinium contrast-enhanced three-dimensional SPGR, MP-RAGE, or TFE axial MRI scan should use the smallest possible axial slice thickness not exceeding 1.5 mm; the associated coronal and sagittal contrast-enhanced T1 sequences can be up to 2.5 mm in slice thickness; this MRI must be obtained =< 21 days prior to step 1 registration; the vendor specific MRI protocols are available for download from the Alzheimer's Disease Neuroimaging Initiative (ADNI)
• Patients must provide study-specific informed consent prior to registration
• PRIOR TO STEP 2 REGISTRATION:
• The following baseline neurocognitive assessments must be completed prior to Step 2 registration: HVLT-R, TMT, and COWA;
• Pathologically (histologically or cytologically) proven diagnosis of solid tumor malignancy within 5 years prior to Step 2 registration
• History and physical examination within 28 days prior to Step 2 registration
• Karnofsky performance status of >= 70 within 28 days prior to Step 2 registration
• Serum creatinine =< 3 mg/dL (265 umol/L) and creatinine clearance >= 30 ml/min
• Blood urea nitrogen (BUN) within institutional upper limit of normal (e.g. < 20 mg/dL)
• Total bilirubin =< 2.5 mg/dL (43 umol/L)
• Patients may have had prior therapy for brain metastasis, including radiosurgery and surgical resection; patients must have completed prior therapy by at least 14 days prior to Step 2 for surgical resection and 7 days for radiosurgery
• Negative serum pregnancy test (in women of childbearing potential) =< 14 days prior to Step 2; women of childbearing potential and men who are sexually active must practice adequate contraception while on study
• Patients who are primary English or French speakers are eligible

You may not qualify if…

• Prior external beam radiation therapy to the brain or whole brain radiation therapy
• Planned cytotoxic chemotherapy during the WBRT only; patients may have had prior chemotherapy
• Radiographic evidence of hydrocephalus or other architectural distortion of the ventricular system, including placement of external ventricular drain or ventriculoperitoneal shunt
• Severe, active co-morbidity defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
• Transmural myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• Chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy at the time of registration
• Severe hepatic disease defined as a diagnosis of Child-Pugh class B or C hepatic disease
• Renal tubular acidosis or metabolic acidosis
• Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4 count < 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration; Note also that HIV testing is not required for eligibility for this protocol
• Pregnant or lactating women, or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
• Prior allergic reaction to memantine (memantine hydrochloride)
• Current alcohol or drug abuse (may exacerbate lethargy/dizziness with memantine)
• Intractable seizures while on adequate anticonvulsant therapy-more than 1 seizure per month for the past 2 months
• Patients with definitive leptomeningeal metastases
• Patients with brain metastases from primary germ cell tumors, small cell carcinoma, unknown primary, or lymphoma
• Contraindication to magnetic resonance (MR) imaging such as implanted metal devices or foreign bodies
• Contraindication to gadolinium contrast administration during MR imaging, such as allergy or insufficient renal function
• Current use of (other N-methyl D-aspartate [NMDA] antagonists) amantadine, ketamine, or dextromethorphan

Where it is running

• Banner MD Anderson Cancer Center — Gilbert, Arizona, United States
• Banner University Medical Center - Tucson — Tucson, Arizona, United States
• Providence Saint Joseph Medical Center/Disney Family Cancer Center — Burbank, California, United States
• Mercy San Juan Medical Center — Carmichael, California, United States
• City of Hope Comprehensive Cancer Center — Duarte, California, United States
• UC San Diego Moores Cancer Center — La Jolla, California, United States
• Kaiser Permanente Los Angeles Medical Center — Los Angeles, California, United States
• Los Angeles County-USC Medical Center — Los Angeles, California, United States
• USC / Norris Comprehensive Cancer Center — Los Angeles, California, United States
• Kaiser Permanente Oakland-Broadway — Oakland, California, United States
• Stanford Cancer Institute Palo Alto — Palo Alto, California, United States
• Kaiser Permanente-Rancho Cordova Cancer Center — Rancho Cordova, California, United States
• Rohnert Park Cancer Center — Rohnert Park, California, United States
• Sutter Cancer Centers Radiation Oncology Services-Roseville — Roseville, California, United States
• The Permanente Medical Group-Roseville Radiation Oncology — Roseville, California, United States
• Mercy Cancer Center - Sacramento — Sacramento, California, United States
• Sutter Medical Center Sacramento — Sacramento, California, United States
• University of California San Diego — San Diego, California, United States
• California Pacific Medical Center-Pacific Campus — San Francisco, California, United States
• Stanford Cancer Center South Bay — San Jose, California, United States
• Kaiser Permanente Medical Center - Santa Clara — Santa Clara, California, United States
• Kaiser Permanente Cancer Treatment Center — South San Francisco, California, United States
• Sutter Solano Medical Center/Cancer Center — Vallejo, California, United States
• Rocky Mountain Cancer Centers-Boulder — Boulder, Colorado, United States
• Lewis and Faye Manderson Cancer Center — Tuscaloosa, Alabama, United States

Full record on ClinicalTrials.gov

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