Riluzole in Women With Stage I, Stage II, or Stage IIIA Breast Cancer - Full Text View

Sponsor:	Barbara Ann Karmanos Cancer Institute
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:	NCT00903214

Purpose

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.

Condition	Intervention	Phase
Breast Cancer	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	Phase I

Study Type:	Interventional
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

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Riluzole

U.S. FDA Resources

Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]

Enrollment:	0
Study Start Date:	May 2009
Study Completion Date:	June 2011
Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Intervention Details:

100 mg orally twice a day, tablets self-administered, administered from day -14 to day 0 (scheduled surgery and preserve tissue for biormarker analysis)

Other Name: RILUTEK

Pre-treatment, day -15 but may be done any time after enrollment but before surgery.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00903214

Sponsors and Collaborators

Barbara Ann Karmanos Cancer Institute

National Cancer Institute (NCI)

Investigators

Principal Investigator:

David H. Gorski, MD, PhD, FACSw

Barbara Ann Karmanos Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	David H. Gorski, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:	NCT00903214 History of Changes
Other Study ID Numbers:	CDR0000641180, P30CA022453, WSU-2008-120
Study First Received:	May 15, 2009
Last Updated:	December 5, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Barbara Ann Karmanos Cancer Institute:

stage I breast cancer
stage II breast cancer
stage IIIA breast cancer

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Riluzole
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants

ClinicalTrials.gov processed this record on February 09, 2012