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

Not Applicable

Withdrawn

• Conditions: Stage II Breast Cancer; Stage IIIA Breast Cancer; Triple-negative Breast Cancer
• Interventions: Drug: vorinostat; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis

• Registration Number: NCT01695057
• Lead Sponsor: University of Southern California

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2012-09-24
• Study First Submitted QC: 2012-09-26
• Study First Posted: 2012-09-27
• Study Start: 2012-10
• Status Verified: 2014-01
• Last Update Submitted: 2014-01-27
• Last Update Posted: 2014-01-28
• Primary Completion: 2014-10
• Study Completion: 2015-10

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Female
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (vorinostat and surgery)	therapeutic conventional surgery	Patients receive vorinostat 400 mg daily PO on days 1-21 followed by surgery within 14 days.
Treatment (vorinostat and surgery)	laboratory biomarker analysis	Patients receive vorinostat 400 mg daily PO on days 1-21 followed by surgery within 14 days.
Treatment (vorinostat and surgery)	vorinostat	Patients receive vorinostat 400 mg daily PO on days 1-21 followed by surgery within 14 days.

Primary Outcome Measures

Name	Time	Method
Combined PR/ER response	21 days	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

Name	Time	Method
Grade 3 or 4 toxicities using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0	Within 3 days prior to surgery	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.