Riluzole and Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases

A Phase I Trial of Riluzole in Combination With Radiation Therapy in Patients Undergoing Whole Brain Radiation Therapy for Brain Metastasis

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.

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