Metabotropic Glutamate Receptor-1 (mGluR1): Validation of a Serendipitously Discovered Molecular Target for Breast Cancer Treatment
18 Years
N/A
Female
Breast Cancer
Trial Information
Metabotropic Glutamate Receptor-1 (mGluR1): Validation of a Serendipitously Discovered Molecular Target for Breast Cancer Treatment
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Inhibition of downstream targets of the mGluR1 signaling cascade, specifically downregulation of PLCβ activity
Outcome Time Frame:
Pre and Post-treatment with RILUTEK® (riluzole) administration
Safety Issue:
No
Principal Investigator
David H. Gorski, MD, PhD, FACSw
Investigator Role:
Principal Investigator
Investigator Affiliation:
Barbara Ann Karmanos Cancer Institute
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000641180
NCT ID:
NCT00903214
Start Date:
May 2009
Completion Date:
June 2011
Related Keywords:
- Breast Cancer
- stage I breast cancer
- stage II breast cancer
- stage IIIA breast cancer
- Breast Neoplasms
Name | Location |
|---|
