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Phase II Trial of Suberoylanilide Hydroxamic Acid (SAHA, Vorinostat) in Combination With Tamoxifen for Patients With Advanced Breast Cancer Who Have Failed Prior Anti-hormonal Therapy.

Phase 2
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

Phase II Trial of Suberoylanilide Hydroxamic Acid (SAHA, Vorinostat) in Combination With Tamoxifen for Patients With Advanced Breast Cancer Who Have Failed Prior Anti-hormonal Therapy.

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

- 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).

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

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

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

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants With Objective Response (OR)

Outcome Description:

The Objective Response Rate. Response and progression were evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST). Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria. For the purposes of this study, patients were evaluated for response every 8 weeks. In addition to a baseline scan, confirmatory scans were also obtained ≥ 4 weeks following initial documentation of objective response.

Outcome Time Frame:

24 weeks

Safety Issue:


Principal Investigator

Susan Minton, D.O.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

March 2006

Completion Date:

April 2011

Related Keywords:

  • Breast Cancer
  • 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)
  • Breast Neoplasms



Martin Memorial Cancer CenterStuart, Florida  34995-9010
H. Lee Moffitt Cancer Center & Research InstituteTampa, Florida  33612
Fawcett Memorial HospitalPort Charlotte, Florida  33952
University of CaliforniaSan Francisco, California  94108
Bethesda Memorial Hospital Research CenterBoynton Beach, Florida  33435
M.D. Anderson of OrlandoOrlando, Florida  32806
Tallahassee Memorial HealthCare, Inc.Tallahassee, Florida  32308
St. Joseph's/CandlerSavannah, Georgia  31405