A Randomized, Phase III, Double-Blind, Placebo-Controlled Trial of Memantine for Prevention of Cognitive Dysfunction in Patients Receiving Whole-Brain Radiotherapy

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed diagnosis of a solid tumor malignancy
within the past 5 years

- If the original histologic proof of malignancy is > 5 years, then pathological
(i.e., more recent) confirmation is required (e.g., from a systemic metastasis
or brain metastasis)

- Brain metastases must be visible on contrast-enhanced MRI or a contrast enhanced CT
scan (for patients unable to undergo MRI within the past 28 days)

- Patients unable to undergo MRI imaging because of non-compatible devices are
eligible, provided the contrast-enhanced CT scans are obtained and are of
sufficient quality

- Patients who had undergone radiosurgery or surgical resection and are planning
adjuvant whole-brain radiotherapy do not have to have visible disease but do
need a baseline MRI

- Must have stable systemic disease (i.e. no evidence of systemic disease progression
within the past 3 months)

- Patients with brain metastases at initial presentation are eligible and do not need
to demonstrate 3 months of stable scans

PATIENT CHARACTERISTICS:

Inclusion

- Karnofsky performance status 70-100%

- Serum creatinine ≤ 3 mg/dL and creatinine clearance ≥ 30 mL/min

- Total bilirubin ≤ 2.5 mg/dL

- BUN < 20 mg/dL

- Mini-mental status exam score ≥ 18

- Negative serum pregnancy test

- Fertile patients must practice adequate contraception

Exclusion

- 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 respiratory illness
requiring hospitalization or precluding study therapy at the time of
registration

- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

- Pregnant or lactating women

- Prior allergic reaction to memantine hydrochloride

- Current alcohol or drug abuse

- Intractable seizures while on adequate anticonvulsant therapy (i.e., more than one
seizure per month for the past 2 months)

PRIOR CONCURRENT THERAPY:

Inclusion

- At least 14 days but no more than 56 days since prior therapy for brain metastasis,
including radiosurgery and surgical resection

- No systemic chemotherapy for 14 days prior, during, or for 14 days after completion
of whole-brain radiotherapy (WBRT)

Exclusion

- Prior cranial radiotherapy

- Patients may have received up to 3 prior WBRT treatments and still be registered
and randomized on the protocol provided WBRT parameters meet protocol
requirements

- Chronic short-acting benzodiazepine use