A Phase I/II Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Trastuzumab (Herceptin) in Patients With Advanced Metastatic and/or Local Chest Wall Recurrent Her-2 Amplified Breast Cancer

Inclusion Criteria

INCLUSION CRITERIA:

- Histologically confirmed breast cancer

- Must overexpress human epidermal growth factor receptor II (HER-2) gene

- Metastatic or chest wall recurrent disease

- Recurrent or progressive disease while receiving prior trastuzumab
(Herceptin^®) (with or without chemotherapy) OR relapsed within 3 months of
last dose of prior adjuvant trastuzumab for metastatic disease

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion > 20 mm by
conventional techniques or > 10 mm by spiral computed tomography (CT) scan

- Site of measurable disease must not have been irradiated (except chest wall
recurrence treated with adjuvant radiation therapy)

- No untreated brain metastases

- Previously treated brain metastasis responsive to radiotherapy and/or surgery
allowed provided the brain is not the sole site of measurable disease

- Male or female

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

- Adequate organ function:

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9 g/dL

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2 times
upper limit of normal

- Bilirubin ≤ 1.5 mg/dL (3 mg/dL in the presence of Gilbert's disease provided
direct bilirubin is normal)

- Creatinine ≤ 1.5 mg/dL

- Left ventricular ejection fraction (LVEF) normal by nuclear scan or echocardiogram

- Negative pregnancy test

- Fertile patients must use effective contraception

- More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin; 1
week for capecitabine) and recovered

- More than 3 weeks since prior radiotherapy and recovered

- Recovered from prior therapy

- At least 2 weeks since prior valproic acid

- More than 4 weeks since prior investigational agents

- More than 4 weeks since prior lapatinib ditosylate

- Concurrent bisphosphonates allowed provided therapy was initiated prior to study
treatment

EXCLUSION CRITERIA:

- Evidence of PR prolongation or atrioventricular (AV) block by Electrocardiography
(EKG)

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Concurrent radiotherapy for brain metastases

- Concurrent combination antiretroviral therapy for HIV-positive patients

- Other concurrent investigational agents

- Other concurrent anticancer therapy

- Active or ongoing infection

- History of allergic reaction to compounds of similar chemical or biologic composition
to vorinostat or other agents used in study

- Psychiatric illness or social situation that would preclude study compliance

- Other uncontrolled illness

- Pregnant or nursing