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Vorinostat Before Surgery in Treating Patients With Triple-Negative Breast Cancer

This study has been withdrawn prior to enrollment.
(Lack of funding)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Southern California
ClinicalTrials.gov Identifier:
NCT01695057
First received: September 24, 2012
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

This pilot clinical trial studies vorinostat before surgery in treating patients with triple-negative breast cancer. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving enzyme inhibitor therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed


Condition Intervention
Stage II Breast Cancer
Stage IIIA Breast Cancer
Triple-negative Breast Cancer
Drug: vorinostat
Procedure: therapeutic conventional surgery
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 Clinical Trial to Evaluate the Biological Activity of HDAC (Histone Deacetylase Transferases) Inhibition on ER and PR Expression in Triple Negative Invasive Breast Cancer

Resource links provided by NLM:


Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • Combined PR/ER response [ Time Frame: 21 days ] [ Designated as safety issue: No ]
    The proportion of patients who achieve sufficient deacetylation of ER and PR will be estimable with a standard error no greater than +/- 0.05. The proportion of patients who exhibit a sufficient change in ER or PR expression can be estimated with similar precision. In addition, paired t-tests and McNamaraâs test will be used to evaluate whether the effect of vorinostat on deacetylation status or gene expression differs between ER or PR, and linear regression analysis will be used to evaluate the association between deacetylation changes and corresponding expression changes in ER and PR genes.


Secondary Outcome Measures:
  • Grade 3 or 4 toxicities using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Within 3 days prior to surgery ] [ Designated as safety issue: Yes ]
    The toxicities observed will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI Common Toxicity Criteria v4.0 and nadir or maximum values for the laboratory measures), time of onset (i.e. week of treatment), duration, and reversibility or outcome.


Enrollment: 0
Study Start Date: October 2012
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (vorinostat and surgery)
Patients receive vorinostat 400 mg daily PO on days 1-21 followed by surgery within 14 days.
Drug: vorinostat
Given PO
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Procedure: therapeutic conventional surgery
Undergo surgery
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the ability of histone deacetylase (HDAC) inhibition using suberoylanilide hydroxamic acid (SAHA) (vorinostat) to induce expression of the estrogen receptor (ER) and progesterone receptor (PR) genes in solid human triple negative invasive breast cancer.

OUTLINE:

Patients receive vorinostat 400 mg daily orally (PO) on days 1-21 followed by surgery within 14 days.

  Eligibility

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

Inclusion Criteria:

  • Resectable tumor measuring 2cm or more
  • Histologically documented, newly diagnosed, triple negative invasive breast cancer characterized by 0% immunohistochemistry (IHC) nuclear staining for ER-alpha, 0% IHC nuclear staining for PR-alpha, and no amplification of human epidermal growth factor receptor 2 (HER2)/neu by fluorescent in situ hybridization (FISH) using institutional standard; standard IHC assays for ER and PR use antibodies to ER-alpha and PR-alpha and PR-beta
  • Southwest Oncology Group (SWOG) performance status of less than or equal to 1
  • Absolute neutrophil count (ANC) >= 1500/uL
  • Hemoglobin (Hgb) >= 9 g/dL
  • Platelets >= 100,000/uL
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvate transaminase (SGPT) =< 2.5 x upper limit of normal (ULN) or =< 5.0 x ULN in patients with liver metastases
  • Creatinine =< 2.0 mg/dL or calculated creatinine clearance >= 50 ml/min
  • Albumin >= 3 g/dL
  • Potassium >= lower limit normal (LLN)
  • Phosphorous >= LLN
  • Calcium >= LLN
  • Magnesium > LLN
  • Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment
  • Accessible for treatment and follow-up
  • Written informed consent prior to study entry

Exclusion Criteria:

  • HER2/neu amplification by FISH
  • Concurrent neoadjuvant anti-cancer treatment with chemotherapy, endocrine therapy, biologically targeted therapy or radiotherapy
  • Known hypersensitivity to SAHA
  • Preexisting hepatic impairment or renal impairment
  • Intent to receive additional neoadjuvant therapy prior to surgery
  • Concurrent use of an HDAC inhibitor or hydralazine
  • Known diagnosis of human immunodeficiency virus (HIV) infection
  • Major surgery < 4 weeks prior to starting study drug
  • Pregnant or breastfeeding or female of reproductive potential not using an effective method of birth control
  • Other concurrent severe, uncontrolled infection or intercurrent illness, including but not limited to ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
  • Prior antiestrogens (selective estrogen receptor modulator [SERM] or aromatase inhibitors) within 6 months of study entry
  • Underlying medical, psychiatric or social conditions that would preclude patient from receiving treatment
  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: NCT01695057

Sponsors and Collaborators
University of Southern California
Investigators
Principal Investigator: Agustin Garcia University of Southern California
  More Information

No publications provided

Responsible Party: University of Southern California
ClinicalTrials.gov Identifier: NCT01695057     History of Changes
Other Study ID Numbers: 1B-10-10, NCI-2012-01612
Study First Received: September 24, 2012
Last Updated: January 27, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Vorinostat
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014