A Pilot Study of Vorinostat to Restore Sensitivity to Aromatase Inhibitor Therapy
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Duration of Response
研究概览
简要总结
This pilot clinical trial studies vorinostat in treating patients with stage IV breast cancer receiving aromatase inhibitor (AI) therapy. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vorinostat may also help AI therapy work better by making tumor cells more sensitive to the drug
详细描述
PRIMARY OBJECTIVES:
I. Determine the rate of clinical benefit (objective response plus stable disease) for patients treated with cycles consisting of 2 weeks of vorinostat followed by 6 weeks of AI therapy.
SECONDARY OBJECTIVES:
I. Assess the safety and tolerability of vorinostat in patients with metastatic breast cancer.
II. Assess the change in estrogen receptor (ER) expression, measured as the change in fluoroestradiol standard uptake value (FES SUV) using fluoroestradiol-positron emission tomography (FES-PET) completed per protocol 7184 after two weeks of vorinostat therapy and after 8 weeks of therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically proven diagnosis of breast cancer
- •Stage IV disease
- •Patient has previously derived clinical benefit from endocrine therapy, but is no longer deriving benefit to endocrine therapy in the opinion of the treating investigator; patients need to stop AI for at least one week prior to starting vorinostat treatment on this protocol
- •At least one site of measurable disease, as defined by the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Female patient is post menopausal as defined by one of the following; free from menses for > 2 years, surgically sterilized ,FSH and Estradiol in post-menopausal range AND surgical absence of uterus OR chemotherapy induced amenorrhea lasting > 1 year OR currently on ovarian suppression
- •Female patient of childbearing potential has a negative urine or serum (beta-human chorionic gonadotropin [hCG]) pregnancy test within 14 days prior to receiving the first dose of vorinostat
- •Male patient agrees to use two barrier methods of contraception or abstain from intercourse for the duration of the study
- •Absolute neutrophil count (ANC) >= 1,500/mcL
- •Platelets >= 100,000/mcL
- •Hemoglobin >= 9 g/dL
- •Prothrombin Time or international normalized ratio (INR) =< 1.5 x upper limit of normal (ULN) unless receiving therapeutic anticoagulation
- •Partial thromboplastin time (PTT) =< 1.2 times the ULN unless the patient is receiving therapeutic anticoagulation
- •Potassium and magnesium levels within normal limits
- •Calculated creatinine clearance >= 30 mL/min
- •Serum total bilirubin =< 1.5 X ULN
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X ULN
- •Alkaline Phosphatase =< 2.5 X ULN
- •Patient, or the patient's legal representative, has voluntarily agreed to participate by giving written informed consent
- •Patient has a life expectancy of at least 12 weeks in the opinion of the treating investigator
- •Patient is willing to continue on same AI therapy
- •Patient agrees to participate in imaging Protocol 7184 and is separately consented
排除标准
- •Patient has not derived clinical benefit from prior endocrine therapy
- •Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drug(s) other than the imaging protocol 7184
- •Patient has received an ER blocking therapy (selective estrogen receptor modulating [SERM] or downregulating [SERD] i.e. tamoxifen or fulvestrant) within the past 6 weeks
- •Patient had prior treatment with an histone deacetylase (HDAC) inhibitor (e.g., romidespin [Depsipeptide], NSC-630176, MS 275, LAQ-824, belinostat [PXD-101], LBH589, MGCD0103, CRA024781, etc); patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study; patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period
- •Patient is on any systemic steroids that have not been stabilized to the equivalent of =<10 mg/day prednisone during the 30 days prior to the start of the study drugs
- •Patient has known hypersensitivity to the components of study drug or its analogs
- •Patients with uncontrolled brain metastases
- •New York Heart Association (NYHA) Class III or IV congestive heart failure, myocardial infarction within the previous 6 months, corrected QT interval (QTc) > 0.47 seconds, or uncontrolled arrhythmia.
- •Type I Diabetes Mellitus; patients with Type II Diabetes Mellitus will be included as long as their glucose can be controlled to under 200 mg/dL
- •Patient is pregnant or breast feeding, or expecting to conceive or father children within the projected duration of the study
- •Patient with a "currently active" second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled; patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for > 5 years or are considered by their physician to be at less than 30% risk of relapse
- •Patients with known active viral hepatitis
- •Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or is not in the best interest of the patient to participate
研究组 & 干预措施
Treatment (enzyme inhibitor therapy, AI sensitization therapy)
Patients receive vorinostat PO QD for 2 weeks followed by AI therapy comprising anastrozole PO QD, letrozole PO QD, OR exemestane PO QD for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: vorinostat (Drug)
Treatment (enzyme inhibitor therapy, AI sensitization therapy)
Patients receive vorinostat PO QD for 2 weeks followed by AI therapy comprising anastrozole PO QD, letrozole PO QD, OR exemestane PO QD for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (enzyme inhibitor therapy, AI sensitization therapy)
Patients receive vorinostat PO QD for 2 weeks followed by AI therapy comprising anastrozole PO QD, letrozole PO QD, OR exemestane PO QD for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: biopsy (Procedure)
Treatment (enzyme inhibitor therapy, AI sensitization therapy)
Patients receive vorinostat PO QD for 2 weeks followed by AI therapy comprising anastrozole PO QD, letrozole PO QD, OR exemestane PO QD for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: F-18 16 alpha-fluoroestradiol (Radiation)
Treatment (enzyme inhibitor therapy, AI sensitization therapy)
Patients receive vorinostat PO QD for 2 weeks followed by AI therapy comprising anastrozole PO QD, letrozole PO QD, OR exemestane PO QD for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: positron emission tomography (Procedure)
Treatment (enzyme inhibitor therapy, AI sensitization therapy)
Patients receive vorinostat PO QD for 2 weeks followed by AI therapy comprising anastrozole PO QD, letrozole PO QD, OR exemestane PO QD for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: anastrozole (Drug)
Treatment (enzyme inhibitor therapy, AI sensitization therapy)
Patients receive vorinostat PO QD for 2 weeks followed by AI therapy comprising anastrozole PO QD, letrozole PO QD, OR exemestane PO QD for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: letrozole (Drug)
Treatment (enzyme inhibitor therapy, AI sensitization therapy)
Patients receive vorinostat PO QD for 2 weeks followed by AI therapy comprising anastrozole PO QD, letrozole PO QD, OR exemestane PO QD for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: exemestane (Drug)
Treatment (enzyme inhibitor therapy, AI sensitization therapy)
Patients receive vorinostat PO QD for 2 weeks followed by AI therapy comprising anastrozole PO QD, letrozole PO QD, OR exemestane PO QD for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: gene expression analysis (Genetic)
结局指标
主要结局
Duration of Response
时间窗: Up to approximately 5 years
Duration of response will be summarized for responders.
Rate of Clinical Benefit According to RECIST
时间窗: Up to approximately 5 years
Conventional imaging (CT, bone scan) was performed at baseline and at week 8 and tumor response assessed by RECIST criteria
次要结局
- Overall Survival(Time elapsed from the first day of study treatment until death, assessed up to approximately 5 years)
- Progression-free Survival(Time elapsed from the first day of study treatment, until disease progression or death, assessed up to approximately 5 years)
- Percentage of Patients That Experience Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0(Up to approximately 5 years)
研究者
Hannah Linden
Principal Investigator
University of Washington