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Phase II Trial of SAHA & Tamoxifen for Patients With Breast Cancer

This study has been completed.
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute Identifier:
First received: August 15, 2006
Last updated: November 10, 2014
Last verified: November 2014
Phase II trial to explore the efficacy of vorinostat and tamoxifen combined.

Condition Intervention Phase
Breast Cancer Drug: suberoylanilide hydroxamic acid (SAHA, Vorinostat) Drug: tamoxifen citrate (Tamoxifen) Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:

Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Number of Participants With Objective Response (OR) [ Time Frame: 24 weeks ]
    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.

Secondary Outcome Measures:
  • Time to Progression (TTP) [ Time Frame: Up to 30 months ]
    The median response duration in months. Response and progression were evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST).

  • Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: 4 years, 7 months ]
    Safety evaluation according to descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Enrollment: 43
Study Start Date: February 2006
Study Completion Date: August 2012
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vorinostat and Tamoxifen
As outlined in Intervention descriptions
Drug: suberoylanilide hydroxamic acid (SAHA, Vorinostat)
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).
Other Names:
  • SAHA
  • Vorinostat
  • NSC #701852
Drug: tamoxifen citrate (Tamoxifen)
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).
Other Names:
  • Nolvadex
  • Tam
  • Tamoxifen

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).


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
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Please refer to this study by its identifier: NCT00365599

United States, California
University of California
San Francisco, California, United States, 94143
United States, Florida
Bethesda Memorial Hospital Research Center
Boynton Beach, Florida, United States, 33435
M.D. Anderson of Orlando
Orlando, Florida, United States, 32806
Fawcett Memorial Hospital
Port Charlotte, Florida, United States, 33949
Martin Memorial Cancer Center
Stuart, Florida, United States, 34994
Tallahassee Memorial HealthCare, Inc.
Tallahassee, Florida, United States, 32308
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
United States, Georgia
St. Joseph's/Candler
Savannah, Georgia, United States, 31405
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Merck Sharp & Dohme Corp.
Principal Investigator: Susan Minton, D.O. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute Identifier: NCT00365599     History of Changes
Other Study ID Numbers: MCC-14662
Study First Received: August 15, 2006
Results First Received: February 21, 2012
Last Updated: November 10, 2014

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Breast cancer
Suberoylanilide hydroxamic acid (SAHA)
Anti-hormonal therapy
Estrogen receptor positive
Progesterone receptor positive
Metastatic disease
Aromatase inhibitors (Ais)
Histone deacetylase (HDAC) inhibitors
Selective estrogen receptor modulators(SERMS)

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Selective Estrogen Receptor Modulators
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Estrogen Antagonists
Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Modulators
Bone Density Conservation Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on September 21, 2017