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

April 25, 2013 updated by: Barbara Ann Karmanos Cancer Institute

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

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.

Study Overview

Status

Withdrawn

Conditions

Breast Cancer

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Phase

Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

Female

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: N/A
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Measures of proliferation, specifically mitotic rate and expression of Ki-67 Time Frame: Pre and Post treatment with RILUTEK® (riluzole) administration:	Pre and Post treatment with RILUTEK® (riluzole) administration:
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:	Pre and Post treatment with RILUTEK® (riluzole) administration:

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Barbara Ann Karmanos Cancer Institute

Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator: David H. Gorski, MD, PhD, FACSw, Barbara Ann Karmanos Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2009

Primary Completion (Actual)

June 1, 2011

Study Completion (Actual)

June 1, 2011

Study Registration Dates

First Submitted

May 15, 2009

First Submitted That Met QC Criteria