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

Primary Purpose

Breast Cancer

Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
riluzole
polymorphism analysis
axillary lymph node biopsy
digital image analysis
needle biopsy
sentinel lymph node biopsy
therapeutic conventional surgery
Sponsored by
Barbara Ann Karmanos Cancer Institute
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring stage I breast cancer, stage II breast cancer, stage IIIA breast cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

    Outcomes

    Primary Outcome Measures

    Inhibition of downstream targets of the mGluR1 signaling cascade, specifically downregulation of PLCβ activity
    Downregulation of phosphorylated ERK1/2

    Secondary Outcome Measures

    Measures of proliferation, specifically mitotic rate and expression of Ki-67
    Measures of apoptosis, specifically levels of poly(ADP-ribose) polymerase (PAPR) cleavage and caspase III activity

    Full Information

    First Posted
    May 15, 2009
    Last Updated
    April 25, 2013
    Sponsor
    Barbara Ann Karmanos Cancer Institute
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00903214
    Brief Title
    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

    2. Study Status

    Record Verification Date
    April 2013
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Funding ended
    Study Start Date
    May 2009 (undefined)
    Primary Completion Date
    June 2011 (Actual)
    Study Completion Date
    June 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Barbara Ann Karmanos Cancer Institute
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Breast Cancer
    Keywords
    stage I breast cancer, stage II breast cancer, stage IIIA breast cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Intervention Type
    Drug
    Intervention Name(s)
    riluzole
    Other Intervention Name(s)
    RILUTEK
    Intervention Description
    100 mg orally twice a day, tablets self-administered, administered from day -14 to day 0 (scheduled surgery and preserve tissue for biormarker analysis)
    Intervention Type
    Genetic
    Intervention Name(s)
    polymorphism analysis
    Intervention Description
    Pre-treatment, day -15 but may be done any time after enrollment but before surgery.
    Intervention Type
    Procedure
    Intervention Name(s)
    axillary lymph node biopsy
    Intervention Type
    Procedure
    Intervention Name(s)
    digital image analysis
    Intervention Type
    Procedure
    Intervention Name(s)
    needle biopsy
    Intervention Type
    Procedure
    Intervention Name(s)
    sentinel lymph node biopsy
    Intervention Type
    Procedure
    Intervention Name(s)
    therapeutic conventional surgery
    Primary Outcome Measure Information:
    Title
    Inhibition of downstream targets of the mGluR1 signaling cascade, specifically downregulation of PLCβ activity
    Time Frame
    Pre and Post-treatment with RILUTEK® (riluzole) administration
    Title
    Downregulation of phosphorylated ERK1/2
    Time Frame
    Pre and Post treatment with RILUTEK® (riluzole) administration:
    Secondary Outcome Measure Information:
    Title
    Measures of proliferation, specifically mitotic rate and expression of Ki-67
    Time Frame
    Pre and Post treatment with RILUTEK® (riluzole) administration:
    Title
    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:

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    David H. Gorski, MD, PhD, FACSw
    Organizational Affiliation
    Barbara Ann Karmanos Cancer Institute
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

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

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