Clinical trial NCT00903214: Riluzole in Women With Stage I, Stage II, or Stage IIIA Breast Cancer
Official title: Metabotropic Glutamate Receptor-1 (mGluR1): Validation of a Serendipitously Discovered Molecular Target for Breast Cancer Treatment
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Breast Cancer
Keywords: stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
Lead sponsor: Barbara Ann Karmanos Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-05-18
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Inhibition of downstream targets of the mGluR1 signaling cascade, specifically downregulation of PLCβ activity
timeFrame: Pre and Post-treatment with RILUTEK® (riluzole) administration
measure: Downregulation of phosphorylated ERK1/2
timeFrame: Pre and Post treatment with RILUTEK® (riluzole) administration:
Secondary outcomes:
measure: Measures of proliferation, specifically mitotic rate and expression of Ki-67
timeFrame: Pre and Post treatment with RILUTEK® (riluzole) administration:
measure: Measures of apoptosis, specifically levels of poly(ADP-ribose) polymerase (PAPR) cleavage and caspase III activity
timeFrame: Pre and Post treatment with RILUTEK® (riluzole) administration:
Other outcomes:
Locations:
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: David H. Gorski, MD, PhD, FACSw
role: PRINCIPAL_INVESTIGATOR
References: