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

Condition(s) targeted: Breast Cancer

Intervention: suberoylanilide hydroxamic acid (Drug); tamoxifen citrate (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: H. Lee Moffitt Cancer Center and Research Institute

Official(s) and/or principal investigator(s):
Susan Minton, D.O., Principal Investigator, Affiliation: H. Lee Moffitt Cancer Center and Research Institute

Overall contact:
Mensura Lacevic, RN, Phone: 813-745-8304, Email: mensura.lacevic@moffitt.org

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

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.

Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome: Complete response - the disappearance of all target lesions; Partial response - at least a 30% decrease in the sum of the longest diameter of target lesions; Clinical benefits rate

Secondary outcome:

Time to progression; Overall survival; Safety

Pre-treatment and post-treatment ER receptor expression in tumors (optional) and histone acetylation (day 8 (+1)) in tumors and PBMCs from women with easily biopsiable disease, in these patients PK studies will be obtained

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 two 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

- PK sample

- Tumor fine needle aspirate (FNA)

- Peripheral Blood Mononuclear Cells (PBMC)

- Standard labs and Chemistry Profile

- CEA, Ca15-3, Ca 125 (If clinically indicated)

- Pregnancy Test

- CT scans, and MRI

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

Minimum age: 19 Years. Maximum age: N/A. Gender(s): Both.

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 ECOG performance status 0-2

- Patients must be able to give informed consent and able to follow guidelines given in

the study

- Patient must have acceptable organ function, as defined by the following laboratory

parameters: WBC >3. 0x109/L; ANC > 1. 5 x 109/L; Hgb >10. 0g/dL; PLT >100x109/L, Bilirubin < 2. 0 mg/dl, 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 six 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 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 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 three 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

Mensura Lacevic, RN, Phone: 813-745-8304, Email: mensura.lacevic@moffitt.org

University of California, San Francisco, California 94143, United States; Recruiting
Amy DeLuca, Phone: 415-353-7288, Email: delucaa@cc.ucsf.edu
Pamela Munster, M.D., Principal Investigator
Michelle Melisko, M.D., Sub-Investigator
Mark Moasser, M.D., Sub-Investigator
Hope Rugo, M.D., Sub-Investigator

H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, United States; Recruiting
Susan N. Minton, D.O., Principal Investigator
Lodovico Balducci, MD, Sub-Investigator
Loretta Loftus, MD, Sub-Investigator
Martine Exterman, MD, Sub-Investigator
Jill Blair, ARNP, Sub-Investigator
Laurie Sullivan, ARNP, Sub-Investigator
Pamela Vranas, ARNP, Sub-Investigator
Lorraine Hutson, ARNP, Sub-Investigator
Patricia Sullivan, ARNP, Sub-Investigator

Bethesda Memorial Hospital Research Center, Boynton Beach, Florida 33435, United States; Terminated

M.D. Anderson of Orlando, Orlando, Florida 32806, United States; Terminated

Moffitt Cancer Center Clinical Trials Website

Starting date: March 2006
Ending date: April 2015
Last updated: September 22, 2009