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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00903214
• Other study ID #: CDR0000641180
• Secondary ID: P30CA022453WSU-2
• Status: Withdrawn
• Phase: Phase 1
• First received: May 15, 2009
• Last updated: April 25, 2013
• Start date: May 2009
• Est. completion date: June 2011

Study information

• Verified date: April 2013
• Source: Barbara Ann Karmanos Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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

• digital image analysis

• needle biopsy

• sentinel lymph node biopsy

• therapeutic conventional surgery

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Barbara Ann Karmanos Cancer Institute	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Inhibition of downstream targets of the mGluR1 signaling cascade, specifically downregulation of PLCß activity		Pre and Post-treatment with RILUTEK® (riluzole) administration	No
Primary	Downregulation of phosphorylated ERK1/2		Pre and Post treatment with RILUTEK® (riluzole) administration:	No
Secondary	Measures of proliferation, specifically mitotic rate and expression of Ki-67		Pre and Post treatment with RILUTEK® (riluzole) administration:	No
Secondary	Measures of apoptosis, specifically levels of poly(ADP-ribose) polymerase (PAPR) cleavage and caspase III activity		Pre and Post treatment with RILUTEK® (riluzole) administration:	No