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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Window Trial of Vorinostat in Patients With Ductal Carcinoma in Situ (DCIS) of the Breast

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: vorinostat
* Genetic: protein expression analysis
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis
* Procedure: neoadjuvant therapy
* Procedure: therapeutic conventional surgery


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vorinostat<br> | Drug: vorinostat<br> <br> Genetic: protein expression analysis<br> <br> Other: immunohistochemistry staining method<br> <br> Other: laboratory biomarker analysis<br> <br> Procedure: neoadjuvant therapy<br> <br> Procedure: therapeutic conventional surgery<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in Ki-67 compared to baseline Ki-67 |  | 3 days prior to surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in HDAC1 and HDAC6 expression and histone H4 and α-tubulin acetylation in breast tissue and serum samples |  | 3 days prior to surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ductal breast carcinoma in situ