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

NCT01153672 | Completed Results

• 2 other identifiers: 6856NCI-2010-01289
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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

Conditions

Male Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Rate of Clinical Benefit According to RECIST

  Conventional imaging (CT, bone scan) was performed at baseline and at week 8 and tumor response assessed by RECIST criteria

  Up to approximately 5 years

• Duration of Response

  Duration of response will be summarized for responders.

  Up to approximately 5 years

Secondary Outcomes (3)

• Progression-free Survival

  Time elapsed from the first day of study treatment, until disease progression or death, assessed up to approximately 5 years

• Overall Survival

  Time elapsed from the first day of study treatment until death, assessed up to approximately 5 years

• Percentage of Patients That Experience Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0

  Up to approximately 5 years

Study Arms (1)

Treatment (enzyme inhibitor therapy, AI sensitization therapy)

EXPERIMENTAL

Patients receive vorinostat PO QD for 2 weeks followed by AI therapy comprising anastrozole PO QD, letrozole PO QD, OR exemestane PO QD for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

Drug: vorinostat; Other: laboratory biomarker analysis; Procedure: biopsy; Radiation: F-18 16 alpha-fluoroestradiol; Procedure: positron emission tomography; Drug: anastrozole; Drug: letrozole; Drug: exemestane; Genetic: gene expression analysis

Interventions

vorinostat DRUG

Given PO

Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

Treatment (enzyme inhibitor therapy, AI sensitization therapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (enzyme inhibitor therapy, AI sensitization therapy)

biopsy PROCEDURE

Optional correlative studies

Also known as: biopsies

Treatment (enzyme inhibitor therapy, AI sensitization therapy)

F-18 16 alpha-fluoroestradiol RADIATION

Correlative studies

Also known as: F-18 FES, fluorine-18 16 alpha-fluoroestradiol

Treatment (enzyme inhibitor therapy, AI sensitization therapy)

positron emission tomography PROCEDURE

Correlative studies

Also known as: FDG-PET, PET, PET scan, tomography, emission computed

Treatment (enzyme inhibitor therapy, AI sensitization therapy)

anastrozole DRUG

Given PO

Also known as: ANAS, Arimidex, ICI-D1033

Treatment (enzyme inhibitor therapy, AI sensitization therapy)

letrozole DRUG

Given PO

Also known as: CGS 20267, Femara, LTZ

Treatment (enzyme inhibitor therapy, AI sensitization therapy)

exemestane DRUG

Given PO

Also known as: Aromasin, FCE-24304, PNU 155971

Treatment (enzyme inhibitor therapy, AI sensitization therapy)

gene expression analysis GENETIC

Correlative studies

Treatment (enzyme inhibitor therapy, AI sensitization therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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; patients need to stop AI for at least one week prior to starting vorinostat treatment on this protocol
• 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 \[hCG\]) 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 \>= 100,000/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 and magnesium levels within normal limits
• Calculated creatinine clearance \>= 30 mL/min

You may not qualify if:

• 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 \[SERM\] or downregulating \[SERD\] i.e. tamoxifen or fulvestrant) within the past 6 weeks
• Patient had prior treatment with an histone deacetylase (HDAC) inhibitor (e.g., romidespin \[Depsipeptide\], 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, corrected QT interval (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 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

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Breast Neoplasms, Male; Breast Neoplasms

Interventions

Vorinostat; Biopsy; Magnetic Resonance Spectroscopy; 2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole; Anastrozole; Letrozole; exemestane; Gene Expression Profiling

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Genetic Techniques

Results Point of Contact

• Title: Hannah M. Linden, MD
• Organization: University of Washington

hmlinden@u.washington.edu

206-288-6989

Study Officials

• Hannah Linden

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 22, 2010
• First Posted: June 30, 2010
• Study Start: November 1, 2010
• Primary Completion: July 1, 2012
• Study Completion: August 11, 2016
• Last Updated: September 6, 2019
• Results First Posted: November 7, 2014

Record last verified: 2019-08

Locations

US (1)