Clinical trial NCT00566852
Conditions: Cognitive/Functional Effects Metastatic Cancer Neurotoxicity Unspecified Adult Solid Tumor, Protocol Specific
Keywords: cognitive/functional effects neurotoxicity tumors metastatic to brain unspecified adult solid tumor, protocol specific
Sponsor: Radiation Therapy Oncology Group
Start date: 2008-03-01; Completion date: 2016-12-01
Enrollment: 554 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Detailed description:
OBJECTIVES:

Primary

* 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.

Secondary

* 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 cerebrospinal fluid (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.

Arms: arm 1: Whole brain radiation therapy (WBRT) and memantine arm 2: Whole brain radiation therapy (WBRT) and placebo
Interventions: intervention 1: Memantine intervention 2: Placebo intervention 3: Whole brain radiation therapy
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: 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

Protocol documents: