Vorinostat in Treating Patients With Stage IV Breast Cancer Receiving Hormone Therapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Washington
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT01720602
First received: October 31, 2012
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

This pilot clinical trial studies vorinostat in treating patients with stage IV breast cancer receiving hormone therapy. Vorinostat may help hormone therapy work better by making tumor cells more sensitive to the drug.


Condition Intervention
Male Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer
Drug: vorinostat
Drug: anastrozole
Drug: letrozole
Drug: exemestane
Procedure: positron emission tomography
Radiation: F-18 16 alpha-fluoroestradiol
Radiation: fludeoxyglucose F 18
Other: laboratory biomarker analysis

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Vorinostat to Restore Sensitivity to Aromatase Inhibitor Therapy Part B

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Rate of clinical benefit of patients receiving vorinostat/AI combination therapy according to RECIST [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    A 90% score (Wilson) confidence interval will be computed for the rate of clinical benefit.

  • Response rate according to RECIST [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    A 90% score (Wilson) confidence interval will be computed for the response rate.


Secondary Outcome Measures:
  • Duration of response [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Duration of response will be summarized for responders.

  • Progression-free survival (PFS) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Kaplan-Meier survival curves will be used to describe PFS.

  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Kaplan-Meier survival curves will be used to describe overall survival.


Estimated Enrollment: 14
Study Start Date: November 2012
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (vorinostat, AI therapy)
Patients receive vorinostat PO 5 days a week for 3 weeks. Patients also receive AI therapy comprising either anastrozole PO daily, letrozole PO daily, or exemestane PO daily for 4 weeks. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity.
Drug: vorinostat
Given PO
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Drug: anastrozole
Given PO
Other Names:
  • ANAS
  • Arimidex
  • ICI-D1033
Drug: letrozole
Given PO
Other Names:
  • CGS 20267
  • Femara
  • LTZ
Drug: exemestane
Given PO
Other Names:
  • Aromasin
  • FCE-24304
  • PNU 155971
Procedure: positron emission tomography
Correlative studies
Other Names:
  • FDG-PET
  • PET
  • PET scan
  • tomography, emission computed
Radiation: F-18 16 alpha-fluoroestradiol
Correlative studies
Other Names:
  • F-18 FES
  • fluorine-18 16 alpha-fluoroestradiol
Radiation: fludeoxyglucose F 18
Correlative studies
Other Names:
  • 18FDG
  • FDG
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Estimate the rate of clinical benefit (objective response plus stable disease) for patients treated with 28-day cycles of vorinostat (first 5 consecutive days each week for day 1-21) concurrent with daily aromatase inhibitor (AI) therapy (all 28 days).

SECONDARY OBJECTIVES:

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

II. Assess the change in estrogen receptor (ER) expression, measured as the change in F-18 16 alpha-fluoroestradiol (FES) standardized uptake value (SUV) using FES positron emission tomography (PET) completed per protocol 7184 after two weeks of vorinostat and AI therapy and after 8 weeks of therapy.

III. Assess tumor metabolic response, measured as the change in fludeoxyglucose F 18 (FDG) SUV using FDG PET completed per protocol 7184 after two weeks of vorinostat and AI 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), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) tumor expression after two weeks of vorinostat and AI therapy in patients that consent to optional tissue biopsy procedure.

VI. Assess the time to progression and the overall survival of patients treated with 28-day cycles of vorinostat (first 5 consecutive days each week for day 1-21) concurrent with daily AI therapy (all 28 days).

OUTLINE:

Patients receive vorinostat orally (PO) 5 days a week for 3 weeks. Patients also receive AI therapy comprising either anastrozole PO daily, letrozole PO daily, or exemestane PO daily for 4 weeks. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months until progression, and then annually thereafter.

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically proven diagnosis of breast cancer
  • Stage IV disease
  • Patient has previously derived clinical benefit from endocrine therapy, but is no longer deriving benefit to endocrine therapy in the opinion of the treating investigator
  • At least one site of measurable disease, as defined by the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Female patient is post menopausal as defined by one of the following; free from menses for >= 2 years, surgically sterilized, FSH and estradiol in post-menopausal range AND surgical absence of uterus OR chemotherapy induced amenorrhea lasting > 1 year OR currently on ovarian suppression
  • Female patient of childbearing potential has a negative urine or serum (beta human chorionic gonadotropin [B-hCG]) pregnancy test within 14 days prior to receiving the first dose of vorinostat
  • Male patient agrees to use two barrier methods of contraception or abstain from intercourse for the duration of the study
  • Absolute neutrophil count (ANC) >= 1,500/mcL
  • Platelets >= 50,000/mcL
  • Hemoglobin >= 9 g/dL
  • Prothrombin time or international normalized ratio (INR) =< 1.5 x upper limit of normal (ULN) unless receiving therapeutic anticoagulation
  • Partial thromboplastin time (PTT) =< 1.2 times the ULN unless the patient is receiving therapeutic anticoagulation
  • Potassium (K) levels normal limits
  • Magnesium (Mg) levels normal limits
  • Calculated creatinine clearance >= 30 mL/min

    • Creatinine clearance should be calculated per institutional standard
  • Serum total bilirubin =< 1.5 x ULN
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x ULN
  • Alkaline phosphatase =< 2.5 x ULN
  • Patient, or the patient's legal representative, has voluntarily agreed to participate by giving written informed consent
  • Patient has a life expectancy of at least 12 weeks in the opinion of the treating investigator
  • Patient is willing to continue on same AI therapy
  • Patient agrees to participate in imaging protocol 7184 and is separately consented

Exclusion Criteria:

  • Patient has not derived clinical benefit from prior endocrine therapy
  • Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drug(s) other than the imaging protocol 7184
  • Patient has received an ER blocking therapy (selective estrogen receptor modulating or downregulating selective estrogen receptor modulator [SERM] or selective estrogen receptor degrader [SERD] i.e. tamoxifen or fulvestrant) within the past 6 weeks
  • Patient had prior treatment with an histone deacetylase (HDAC) inhibitor (e.g., romidepsin [Depsipeptide], NSC-630176, MS 275, LAQ-824, belinostat (PXD-101), LBH589, MGCD0103, CRA024781, etc); patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study; patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period
  • Patient is on any systemic steroids that have not been stabilized to the equivalent of =< 10 mg/day prednisone during the 30 days prior to the start of the study drugs
  • Patient has known hypersensitivity to the components of study drug or its analogs
  • Patients with uncontrolled brain metastases
  • New York Heart Association (NYHA) class III or IV congestive heart failure, myocardial infarction within the previous 6 months, QTc > 0.47 seconds, or uncontrolled arrhythmia
  • Type I diabetes mellitus; patients with type II diabetes mellitus will be included as long as their glucose can be controlled to under 200 mg/dL
  • Patient is pregnant or breast feeding, or expecting to conceive or father children within the projected duration of the study
  • Patient with a "currently active" second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled; patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for > 5 years or are considered by their physician to be at less than 30% risk of relapse
  • Patients with known active viral hepatitis
  • Patient has a history or current evidence of any condition, therapy, or laboratory (lab) abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or is not in the best interest of the patient to participate
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01720602

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Hannah M. Linden    206-288-1234      
Principal Investigator: Hannah M. Linden         
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Hannah Linden Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT01720602     History of Changes
Other Study ID Numbers: 7841, NCI-2012-02004, P30CA015704
Study First Received: October 31, 2012
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fluorodeoxyglucose F18
Exemestane
Letrozole
Anastrozole
Vorinostat
Aromatase Inhibitors
Radiopharmaceuticals
Diagnostic Uses of Chemicals
Pharmacologic Actions
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Antineoplastic Agents, Hormonal
Histone Deacetylase Inhibitors

ClinicalTrials.gov processed this record on August 27, 2014