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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Metastatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: riluzole
* Radiation: whole-brain radiation therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Riluzole; Radiation Therapy<br> | Drug: riluzole<br>* The first dose of Riluzole will be day 0 of study enrollment. WBRT must begin within 48 hours of the initiation of Riluzole therapy. At the completion of radiation, Riluzole should be discontinued and steroids should be tapered over the course of 1-3 weeks, at the discretion of the treating physicians.<br>Radiation: whole-brain radiation therapy<br>* Standard whole brain irradiation will be carried out at 250 cGy per day fractions times 15 to a total dose of 3750 cGy using a standard opposed lateral helmet field with the inferior border inclusive of C1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of riluzole |  | 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-term toxicity of riluzole |  | .25 years | 
| Neurocognitive function before and after treatment |  | 2.5 years | 
| MRI response of brain metastasis after treatment |  | 2.5 years | 
| Survival |  | 2.5 years | 
| Response of brain metastasis to treatment as a function of the expression of glutamate receptors |  | 2.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tumors metastatic to brain, unspecified adult solid tumor, protocol specific