Phase II Trial of SAHA & Tamoxifen for Patients With Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: suberoylanilide hydroxamic acid (SAHA, Vorinostat); tamoxifen citrate (Tamoxifen)
Intervention description: 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).; 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).
Intervention MeSH terms: Tamoxifen; Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
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)

Summary:

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

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have cytologically/histologically documented locally advanced or
             metastatic breast cancer with either:

               1. Progression on treatment with any aromatase inhibitor for metastatic disease;

               2. Recurrence while on adjuvant aromatase inhibitors or within 12 months of
                  completion;

               3. Recurrence after having completed adjuvant tamoxifen for at least 12 months;

               4. Patient who are not candidates for or are intolerant of aromatase inhibitor
                  treatment;

               5. Patients are allowed (but not required) to have one prior chemotherapy regimen
                  for metastatic disease.

          -  Tumors must express estrogen or progesterone receptor.

          -  Patients are eligible regardless of the menopausal status.

          -  Age > 18 years old

          -  Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

          -  Patients must be able to give informed consent and able to follow guidelines given in
             the study.

          -  Patients must have acceptable organ function, as defined by the following laboratory
             parameters: white blood count (WBC) >3.0 x 10^9/L; absolute neutrophil count (ANC)
             >1.5 x 10^9/L; hemoglobin (Hgb) >10.0g/dL; platelets (PLT) >100 x 10^9/L, Bilirubin <
             2.0 mg/dl, aspartate aminotransferase/alanine aminotransferase (AST/ALT) < 2.5 X upper
             limit of normal (ULN), Creatinine <1.8 mg/dl (Creatinine clearance >60 ml/min).

          -  Women of childbearing age must have a negative pregnancy test. All patients of
             reproductive potential must use an effective method of contraception during the study
             and 6 months following termination of treatment. (Not applicable to patients with
             bilateral oophorectomy and/or hysterectomy or to female patients who are older than 50
             years and have not had a menstrual cycle in more than one year.

          -  Patients must have measurable disease by RECIST criteria by staging studies performed
             within 30 days of enrollment. For patients with bone only disease: For this protocol
             isolated bone lesions can be classified as target lesions if they are measurable by
             MRI at screening and must be followed by MRI.

          -  Both men and women of all races and ethnic groups are eligible for this trial.

        Exclusion Criteria:

          -  Patients must not have received tamoxifen for metastatic disease.

          -  Patients must not have evidence of significant active infection (e.g., pneumonia,
             cellulitis, wound abscess, etc.) at time of study entry.

          -  Patients must be disease-free of prior invasive malignancies for > 5 years with the
             exception of: curatively-treated basal cell or squamous cell carcinoma of the skin,
             carcinoma in situ of the cervix.

          -  Pregnant and breast-feeding women are excluded from the study because effects on the
             fetus are unknown and there may be a risk of increased fetal wastage.

          -  Patients with uncontrolled central nervous system (CNS) metastasis or a history of
             seizures are excluded. Patients with stable CNS metastasis (either surgically
             resected, treated with gamma knife or stable for 3 months following whole brain
             radiation therapy [WBRT] are eligible). Patients with stable brain metastases will
             need an MRI within 4 weeks prior to start of therapy.

          -  Patients may not be receiving any other investigational agents and must have stopped
             all other histone deacetylase inhibitors (including Valproic acid) or other hormonal
             therapies.

          -  Patients must have discontinued their prior therapies for breast cancer and radiation
             therapy for a minimum of 3 weeks, patient is excluded if radiation therapy was given
             to a single measurable lesion and the disease is otherwise not measurable.

          -  Patients are excluded if they have any known hypersensitivity reaction to tamoxifen.

          -  Patient with a history of blood clots are not eligible.

          -  Women who have abnormal vaginal bleeding and/or endometrial hyperplasia or cancer are
             not eligible.

          -  Patients with evidence of visceral crisis are not eligible for this study.