Memantine in Preventing Side Effects in Patients Undergoing Whole-Brain Radiation Therapy for Brain Metastases From Solid Tumors
Condition: Cognitive/Functional Effects; Metastatic Cancer; Neurotoxicity; Unspecified Adult Solid Tumor, Protocol Specific
MeSH terms: Neurotoxicity Syndromes
Intervention: Memantine; Placebo; Whole brain radiation therapy
Intervention description: Patients began taking memantine(by mouth) while receiving radiation therapy. Patients continued taking memantine for 24 weeks or until doctor thinks it is in their best interest to stop. They started with 5 mg once a day. After a week dose increased to 5 mg twice a day. At week 3, dose increased to 10 mg in the morning and 5 mg in the evening. Weeks 4-24, dose was 10 mg twice a day.; Patients began taking placebo(by mouth) while receiving radiation therapy. Patients continued taking placebo for 24 weeks or until doctor thinks it is in their best interest to stop. They started with 5 mg once a day. After a week dose increased to 5 mg twice a day. At week 3, dose increased to 10 mg in the morning and 5 mg in the evening. Weeks 4-24, dose was 10 mg twice a day.; Whole brain radiation therapy (WBRT) once a day (2.5Gy), five days a week (Monday to Friday) for three weeks, for total fifteen treatments and 37.5 Gy
Intervention MeSH terms: Memantine
Phase: Phase 3
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 554.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: cognitive/functional effects; neurotoxicity; tumors metastatic to brain; unspecified adult solid tumor, protocol specific

Summary:

      RATIONALE: Memantine may be able to decrease side effects caused by whole-brain radiation
      therapy. It is not yet known if memantine is effective in preventing side effects caused by
      whole-brain radiation therapy.

      PURPOSE: This randomized phase III trial is studying memantine to see how well it works
      compared to a placebo in preventing side effects caused by whole-brain radiation therapy in
      patients with brain metastases from solid tumors.
    

Eligibility 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

          -  Blood urea nitrogen (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