Riluzole in Women With Stage I, Stage II, or Stage IIIA Breast Cancer
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.
Genetic: polymorphism analysis
Procedure: axillary lymph node biopsy
Procedure: digital image analysis
Procedure: needle biopsy
Procedure: sentinel lymph node biopsy
Procedure: therapeutic conventional surgery
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Metabotropic Glutamate Receptor-1 (mGluR1): Validation of a Serendipitously Discovered Molecular Target for Breast Cancer Treatment|
- Inhibition of downstream targets of the mGluR1 signaling cascade, specifically downregulation of PLCβ activity [ Time Frame: Pre and Post-treatment with RILUTEK® (riluzole) administration ] [ Designated as safety issue: No ]
- Downregulation of phosphorylated ERK1/2 [ Time Frame: Pre and Post treatment with RILUTEK® (riluzole) administration: ] [ Designated as safety issue: No ]
- Measures of proliferation, specifically mitotic rate and expression of Ki-67 [ Time Frame: Pre and Post treatment with RILUTEK® (riluzole) administration: ] [ Designated as safety issue: No ]
- Measures of apoptosis, specifically levels of poly(ADP-ribose) polymerase (PAPR) cleavage and caspase III activity [ Time Frame: Pre and Post treatment with RILUTEK® (riluzole) administration: ] [ Designated as safety issue: No ]
|Study Start Date:||May 2009|
|Study Completion Date:||June 2011|
|Primary Completion Date:||June 2011 (Final data collection date for primary outcome measure)|
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00903214
|Principal Investigator:||David H. Gorski, MD, PhD, FACSw||Barbara Ann Karmanos Cancer Institute|