|Phase III||Supportive care, Tissue collection/Repository, Treatment||Closed||18 and over||NCI, Other||CDR0000577872|
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.
Further Study Information
- Determine whether the addition of memantine hydrochloride to whole-brain radiotherapy (WBRT) preserves cognitive function, specifically memory, as measured by the Hopkins Verbal Learning Test for delayed recall (HVLT-delayed recall), over that of placebo and WBRT in patients with brain metastases at 24 weeks from the start of drug treatment.
- Determine whether the addition of memantine hydrochloride preserves cognitive function, specifically memory, as measured by the HVLT-delayed recall at 8 weeks, 16 weeks, and 12 months from the start of drug treatment.
- Determine whether the addition of memantine hydrochloride increases time to neurocognitive failure as measured by cognitive decline on a battery of tests including the HVLT for free recall, delayed recall, and delayed recognition; the Controlled Word Association Test (COWAT); the Trail Making Test Parts A and B (TMT); the Medical Outcomes Scale-Cognitive Functioning Subscale (MOS); and the Mini-Mental Status Examination (MMSE).
- Evaluate the potential benefit of memantine hydrochloride in change and overall quality of life, as measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) subscale.
- Determine whether the addition of memantine hydrochloride increases progression-free survival.
- Determine whether the addition of memantine hydrochloride increases overall survival.
- Compare adverse events between the treatment arms according to the CTCAE v3.0 criteria.
- Collect serum, plasma, buffy coat cells, urine, and CSF for future translational research analyses.
OUTLINE: This is a multicenter study. Patients are stratified according to recursive partitioning analysis (RPA) prognostic class (class I vs class II with controlled systemic disease) and prior surgical therapy (none vs radiosurgery or surgical resection). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo whole-brain radiotherapy (WBRT) 5 days a week for 3 weeks (15 fractions). Patients also receive oral memantine hydrochloride once daily beginning on day 1 of WBRT and continuing for 24 weeks.
- Arm II: Patients undergo WBRT as in arm I. Patients also receive oral placebo once daily beginning on day 1 of WBRT and continuing for 24 weeks.
After completion of study treatment, patients are followed at 6 months, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.
- 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
- 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
- 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:
- 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)
- 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
Trial Lead Organizations/Sponsors
Radiation Therapy Oncology GroupNational Cancer Institute
|Paul D. Brown, MD||Study Chair|
|Christina A. Meyers|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00566852
Information obtained from ClinicalTrials.gov on November 20, 2012
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