Vorinostat in Treating Women With Ductal Carcinoma in Situ of the Breast

University of California San Francisco (UCSF)

Status and phase

Completed

Phase 1

Conditions

Breast Cancer

Treatments

Other: laboratory biomarker analysis

Genetic: protein expression analysis

Drug: vorinostat

Procedure: therapeutic conventional surgery

Other: immunohistochemistry staining method

Procedure: neoadjuvant therapy

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00788112

H10367-31833

UCSF-077532

UCSF-07031833

CDR0000617655

Details and patient eligibility

About

RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This clinical trial is studying how well vorinostat works in treating women with ductal carcinoma in situ of the breast.

Full description

OBJECTIVES:

To evaluate the in vivo molecular and biological effects of vorinostat by analyzing changes in proliferation and apoptosis, histone acetylation, and HDAC protein expression in women with ductal carcinoma in situ of the breast.

OUTLINE: Patients receive oral vorinostat twice a day for 3 days in the absence of unacceptable toxicity. Patients then undergo lumpectomy or mastectomy 2 hours after the last dose of vorinostat.

Blood and tissue samples are collected at baseline and during surgery for biomarker laboratory studies. Samples are analyzed by immunohistochemistry for Ki-67, HDAC1 and HDAC6 protein expression, and histone H4 and α-tubulin acetylation.

After completion of study therapy, patients are followed for 1 month and then every 6 months for 5 years.

Enrollment

17 patients

Sex

Female

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed (by core biopsy) ductal carcinoma in situ
- Stage 0 disease
Hormone receptor status not specified

PATIENT CHARACTERISTICS:

Menopausal status not specified
ECOG performance status 0-2
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 9 g/dL
Potassium and magnesium levels normal
Prothrombin time or INR ≤ 1.5 times upper limit of normal (ULN) (unless the patient is receiving therapeutic anticoagulation)
Partial thromboplastin time ≤ 1.2 times ULN (unless the patient is receiving therapeutic anticoagulation)
Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use 2 effective barrier methods of contraception
No known psychiatric or substance abuse disorder that would preclude cooperation with the study requirements
No active hepatitis A, B, or C infection
No active HIV infection
No other active infection
No other malignancy within the past 5 years
No condition that would interfere with the absorption or intake of vorinostat
No history or current evidence of any condition or laboratory abnormality that would confound study results, interfere with the patient's participation in the full duration of the study, or that would not be in the best interest of the patient to participate

PRIOR CONCURRENT THERAPY:

More than 2 weeks since prior IV antibiotics, antivirals, or antifungals
No prior gastrointestinal surgery or other procedure that would interfere with the absorption or intake of vorinostat
No prior or concurrent therapy with any other HDAC inhibitor, including valproic acid
No prior treatment with any other investigational agent
No concurrent systemic steroids
No concurrent anticancer chemotherapy, radiotherapy, biological therapy, or other investigational therapy