Conditions: Breast Cancer
Keywords: Breast cancer Suberoylanilide hydroxamic acid (SAHA) Vorinostat Tamoxifen Anti-hormonal therapy Estrogen receptor positive Progesterone receptor positive Metastatic disease Aromatase inhibitors (Ais) Histone deacetylase (HDAC) inhibitors Selective estrogen receptor modulators(SERMS)
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 43
Healthy volunteers: no

Brief summary:
Phase II trial to explore the efficacy of vorinostat and tamoxifen combined.

Detailed description:
Phase II trial to explore the efficacy of vorinostat and tamoxifen combined. Tamoxifen will be given once daily, continuously. Vorinostat will be given daily for 3 out of 4 weeks (a cycle). Responses will be assessed (restaged) after 2 cycles and toxicities will be captured continuously. Eligible patients will receive treatment in consecutive 4-week cycles, until progression of disease or unacceptable toxicity. Patients will be followed for evaluation of safety for at least 30 days after the last dose of the study drug.

Tests will be obtained pre-and post vorinostat treatment and correlated with plasma levels of vorinostat at the time of tumor biopsy and vorinostat doses; the tests will consist of:

* Patient history
* Physical exam (including height and weight)
* Toxicity assessment
* Pharmacokinetic (PK) sample
* Tumor fine needle aspirate (FNA)
* Peripheral Blood Mononuclear Cells (PBMC)
* Standard labs and Chemistry Profile
* Carcinoembryonic antigen (CEA), cancer antigen (Ca) 15-3, Ca 125 (If clinically indicated)
* Pregnancy Test
* Computed tomography (CT) scans, and magnetic resonance imaging (MRI)

Documentation of response and progression will be evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST).

Arms:
arm 1: As outlined in Intervention descriptions

Interventions: intervention 1: suberoylanilide hydroxamic acid (SAHA, Vorinostat) intervention 2: tamoxifen citrate (Tamoxifen)
Intervention descriptions: intervention 1: Vorinostat will be used to potentiate the effects of tamoxifen or overcome tamoxifen resistance. All patients will receive vorinostat at 400 mg by mouth (po) daily for 3 out of 4 weeks. Responses will be assessed after 2 cycles (8 weeks + 4 days). intervention 2: Tamoxifen will be given once daily at 20 mg. Tamoxifen will be given continuously. Responses will be assessed after 2 cycles (8 weeks + 4 days).

Protocol document: