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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

18 Years
Not Enrolling
Stage II Breast Cancer, Stage IIIA Breast Cancer, Triple-negative Breast Cancer

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Trial Information

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


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.


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

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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Combined PR/ER response

Outcome Description:

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.

Outcome Time Frame:

21 days

Safety Issue:


Principal Investigator

Agustin Garcia

Investigator Role:

Principal Investigator

Investigator Affiliation:

USC/Norris Comprehensive Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

October 2012

Completion Date:

October 2015

Related Keywords:

  • Stage II Breast Cancer
  • Stage IIIA Breast Cancer
  • Triple-negative Breast Cancer
  • Breast Neoplasms