Clinical Trial: Vorinostat in Treating Patients With Stage IV Breast Cancer Receiving Aromatase Inhibitor Therapy

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Pilot Study of Vorinostat to Restore Sensitivity to Aromatase Inhibitor Therapy

Brief Summary: This pilot clinical trial studies vorinostat in treating patients with stage IV breast cancer receiving aromatase inhibitor (AI) therapy. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vorinostat may also help AI therapy work better by making tumor cells more sensitive to the drug

Detailed Summary:

PRIMARY OBJECTIVES:

I. Determine the rate of clinical benefit (objective response plus stable disease) for patients treated with cycles consisting of 2 weeks of vorinostat followed by 6 weeks of AI therapy.

SECONDARY OBJECTIVES:

I. Assess the safety and tolerability of vorinostat in patients with metastatic breast cancer.

II. Assess the change in estrogen receptor (ER) expression, measured as the change in fluoroestradiol standard uptake value (FES SUV) using fluoroestradiol-positron emission tomography (FES-PET) completed per protocol 7184 after two weeks of vorinostat therapy and after 8 weeks of therapy.

III. Assess tumor metabolic response, measured as the change in fluorodeoxyglucose (FDG) SUV using FDG PET completed per protocol 7184 after two weeks of vorinostat therapy and after 8 weeks of therapy.

IV. Assess the change in hormone levels (estradiol, estrone, follicle-stimulating hormone [FSH], sex binding globulin, testosterone, and free testosterone) after 8 weeks of therapy.

V. Assess the change in ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), androgen receptor (AR), epithelial growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) tumor expression after two weeks of vorinostat therapy in patients that consent to optional tissue biopsy procedure.

VI. Assess the time to progression and the overall survival of patients treated with cycles of 2 weeks of vorinostat followed by 6 weeks of AI.

OUTLINE:

  • Rate of Clinical Benefit According to RECIST [ Time Frame: Up to approximately 5 years ]

    A 90% score (Wilson) confidence interval will be computed for the response rate and the rate of clinical benefit. The radiological (by computed tomography [CT]) response rate of vorinostat will be determined by tumor measurements assessed by modified RECIST criteria.

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) assessed by CT, Clinical Benefit was defined as an objective response (complete response [CR], partial response [PR]) or stable disease [SD]). CR=the disappearance of all target lesions; PR=at least a 30% decrease in the sum of the longest diameter (LD) of target lesions; SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started; PD=at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum of the LD recorded since the treatment started or the appearance of 1 or more new lesions.

  • Duration of Response [ Time Frame: Up to approximately 5 years ]
    Duration of response will be summarized for responders.


    • Original Primary Outcome:

    • Rate of clinical benefit [ Time Frame: At 30 months ]
    • Duration of Response [ Time Frame: At 30 months ]
    • Overall survival [ Time Frame: At 30 months ]


    Current Secondary Outcome:

    • Progression-free Survival [ Time Frame: Time elapsed from the first day of study treatment, until disease progression or death, assessed up to approximately 5 years ]
      Kaplan-Meier survival curves will be used to describe progression-free survival. For progression-free survival, patients without documented disease progression or death will be treated as censored observations on the date of the last tumor assessment.
    • Overall Survival [ Time Frame: Time elapsed from the first day of study treatment until death, assessed up to approximately 5 years ]
      Kaplan-Meier survival curves will be used to describe overall survival. Overall survival time will be censored on the last date the patient was known to be alive.
    • Percentage of Patients That Experience Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 [ Time Frame: Up to approximately 5 years ]


    Original Secondary Outcome:

    • Percentage of patients that experience adverse events as assessed by CTCAE version 3.0 [ Time Frame: 2 years after last patient end of treatment visit ]
    • Comparison of overall rate of clinical benefit of single agent schedule of vorinostat and AI to combined therapy [ Time Frame: 2 years after last patient end of treatment visit ]
    • Level and change of ER expression in multiple lesions [ Time Frame: After 2 weeks of vorinostat treatment ]
    • Hormone levels [ Time Frame: At baseline and after 8 weeks of treatment ]


    Information By: University of Washington

    Dates:
    Date Received: June 22, 2010
    Date Started: November 2010
    Date Completion: July 2017
    Last Updated: November 4, 2016
    Last Verified: November 2016