Clinical trial NCT00365599: Phase II Trial of SAHA & Tamoxifen for Patients With Breast Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
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)
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2006-08-17
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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).

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.

Primary outcomes:
measure: Number of Participants With Objective Response (OR)
timeFrame: 24 weeks
Secondary outcomes:
measure: Time to Progression (TTP)
timeFrame: Up to 30 months
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: 4 years, 7 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California
state: California
city: Boynton Beach
country: United States
facility: Bethesda Memorial Hospital Research Center
state: Florida
city: Orlando
country: United States
facility: M.D. Anderson of Orlando
state: Florida
city: Port Charlotte
country: United States
facility: Fawcett Memorial Hospital
state: Florida
city: Stuart
country: United States
facility: Martin Memorial Cancer Center
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Memorial HealthCare, Inc.
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Savannah
country: United States
facility: St. Joseph's/Candler
state: Georgia
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Susan Minton, D.O.
role: PRINCIPAL_INVESTIGATOR
References: