Riluzole in Women With Stage I, Stage II, or Stage IIIA Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Studying samples of tumor tissue and blood from patients with cancer in the laboratory may help doctors identify biomarkers related to cancer. Riluzole may help slow the growth of tumor cells. PURPOSE: This phase I trial is studying riluzole in women with stage I, stage II, or stage IIIA breast cancer.

Detailed Description
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OBJECTIVES: Primary To evaluate the effects of glutamate receptor blockade with riluzole on cellular pathways important in the genesis and progression of disease in women with stage I-IIIA breast cancer by examining components of the mGluR1 signaling pathway in the pre- and post-treatment tumor samples to determine if glutamate blockade affects signaling through this pathway. Secondary To determine whether treatment with riluzole affects the proliferation and apoptosis in a manner suggesting a potential for therapeutic effectiveness. To determine whether treatment with riluzole causes objectively measurable tumor shrinkage. OUTLINE: Patients receive oral riluzole twice daily on days -14 to 0. Approximately 12 hours after completion of riluzole therapy patients undergo standard surgery (i.e., partial or total mastectomy) along with sentinel lymph node biopsy (for patients with node-negative disease) or full axillary dissection (for patients with node-positive disease) on day 0. Patients undergo 3-dimensional image assessment at pre- and post-treatment by Computerized Ultrasound Risk Evaluation (C.U.R.E.). Patients undergo core needle biopsy at baseline and during surgery for biomarker analysis (e.g., mGluR1) by IHC, western blotting, and RT-PCR. Blood samples are collected for GRM1 polymorphism analysis. After completion of study treatment, patients are followed every 6 months for 1 year and then according to standard-of-care thereafter.

Official Title
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Metabotropic Glutamate Receptor-1 (mGluR1): Validation of a Serendipitously Discovered Molecular Target for Breast Cancer Treatment

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: riluzole
* Genetic: polymorphism analysis
* Procedure: axillary lymph node biopsy
* Procedure: digital image analysis
* Procedure: needle biopsy
* Procedure: sentinel lymph node biopsy
* Procedure: therapeutic conventional surgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of adenocarcinoma of the breast Stage I (T1c)-IIIA disease meeting the following criteria: Large enough (> 1 cm) to undergo additional multiple core needle biopsies preoperatively Surgically resectable for cure or palliation without first requiring neoadjuvant chemotherapy Patients who have previously been treated for breast cancer, but are judged to have developed a new primary cancer, rather than a recurrence, are eligible PATIENT CHARACTERISTICS: ECOG performance status 0-1 ANC ≥ 1,000/mm³ Platelet count ≥ 50,000/mm³ Liver function tests ≤ 3 times upper limit of normal (ULN) Total bilirubin ≤ 2 times ULN Creatinine ≤ 1.5 mg/dL INR ≤ 25% normal limits Not pregnant or nursing No known history of HIV or AIDS No known history of hepatitis B or C No history of vertigo or Ménière's type of disorder No history of allergic reaction to riluzole or similar compounds PRIOR CONCURRENT THERAPY: No prior estrogen blockers, chemotherapy, radiotherapy, biological therapy, or surgery for the treatment of breast cancer

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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

| Intervention/Treatment |
| --- |
|Drug: riluzole|100 mg orally twice a day, tablets self-administered, administered from day -14 to day 0 (scheduled surgery and preserve tissue for biormarker analysis)|
|Genetic: polymorphism analysis|Pre-treatment, day -15 but may be done any time after enrollment but before surgery.|
|Procedure: axillary lymph node biopsy|nan|
|Procedure: digital image analysis|nan|
|Procedure: needle biopsy|nan|
|Procedure: sentinel lymph node biopsy|nan|
|Procedure: therapeutic conventional surgery|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inhibition of downstream targets of the mGluR1 signaling cascade, specifically downregulation of PLCβ activity |  | Pre and Post-treatment with RILUTEK® (riluzole) administration | 
| Downregulation of phosphorylated ERK1/2 |  | Pre and Post treatment with RILUTEK® (riluzole) administration: | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measures of proliferation, specifically mitotic rate and expression of Ki-67 |  | Pre and Post treatment with RILUTEK® (riluzole) administration: | 
| Measures of apoptosis, specifically levels of poly(ADP-ribose) polymerase (PAPR) cleavage and caspase III activity |  | Pre and Post treatment with RILUTEK® (riluzole) administration: | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I breast cancer, stage II breast cancer, stage IIIA breast cancer