Clinical trial NCT01695057: Vorinostat Before Surgery in Treating Patients With Triple-Negative Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Stage II Breast Cancer
Stage IIIA Breast Cancer
Triple-negative Breast Cancer
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2012-09-27
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Combined PR/ER response
timeFrame: 21 days
Secondary outcomes:
measure: Grade 3 or 4 toxicities using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
timeFrame: Within 3 days prior to surgery
Other outcomes:
Locations:
Study officials:
affiliation: University of Southern California
name: Agustin Garcia
role: PRINCIPAL_INVESTIGATOR
References: