riluzole and whole-brain radiation therapy in treating patients with brain metastases

Conditions: Metastatic Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Summary: rationale: radiation therapy uses high energy x-rays to kill tumor cells. drugs, such as riluzole, may make tumor cells more sensitive to radiation therapy. giving riluzole together with whole-brain radiation therapy may kill more tumor cells. purpose: this phase i trial is studying the side effects and best dose of riluzole when given together with whole-brain radiation therapy in treating patients with brain metastases.

objectives: primary * to determine the maximum tolerated dose of riluzole that can be administered concurrently with standard whole-brain radiotherapy (wbrt) in patients with multiple brain metastases. secondary * to determine the long-term toxicity of riluzole when administered with wbrt. * to assess neurocognitive function before and after treatment with riluzole and wbrt. * to determine the mri response of brain metastasis after treatment with riluzole and wbrt. * to compare survival of patients treated with riluzole and wbrt to published historical data for patients with brain metastases. * to evaluate the response of brain metastasis to riluzole and wbrt as a function of the expression of glutamate receptors on the primary tumor specimen. outline: this is a dose-escalation study of riluzole. patients receive oral riluzole twice daily beginning on day 0. beginning within 2 days after the initiation of riluzole, patients undergo whole-brain radiotherapy for 15 fractions. patients undergo neurocognitive and quality-of-life assessments at baseline, at 5 weeks, and at 3 months. tumor tissue samples are collected for laboratory biomarker studies. after completion of study treatment, patients are followed up at 6 weeks, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Eligibility criteria:
disease characteristics: * histologically confirmed solid tumor * has ≥ 2 brain metastases as demonstrated by baseline mri * patients with only 1 metastasis are eligible provided the metastasis is too large for radiosurgery and not amenable to surgical resection * not being considered for surgical resection * eligible to undergo whole-brain radiotherapy (wbrt) patient characteristics: * ecog performance status 0-2 * anc ≥ 1,000/μl * platelet count ≥ 50,000/μl * total bilirubin ≤ 1.5 times upper limit of normal (uln) * ast/alt ≤ 1.5 times uln * inr ≤ 1.5 times uln * sodium normal * thyroid-stimulating hormone normal * negative pregnancy test * fertile patients must use effective contraception before, during, and for ≥ 6 months after completion of study treatment * no headaches, disequilibrium, vertigo, or dizziness * no known history of hepatitis b or c * no concurrent serious systemic disorder (including active infection) that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator * no history of allergic reactions attributed to riluzole prior concurrent therapy: * no prior wbrt * at least 2 weeks since prior systemic chemotherapy * no systemic chemotherapy during and for ≥ 3 weeks after completion of wbrt * radiosurgical boosts to ≤ 3 metastases allowed, based on the discretion of the treating radiation oncologist

Keywords: tumors metastatic to brain unspecified adult solid tumor, protocol specific