A Phase I/II Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Trastuzumab (Herceptin) in Patients With Advanced Metastatic and/or Local Chest Wall Recurrent Her-2 Amplified Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 25
- 主要终点
- Response Rate
研究概览
简要总结
This phase I/II trial is studying the side effects and best dose of vorinostat when given together with trastuzumab and to see how well they work in treating patients with metastatic breast canceror breast cancer that has recurred in the chest wall. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Vorinostat and trastuzumab also may stop the growth of tumor cells by blocking blood flow to the tumor. Giving vorinostat together with trastuzumab may be a better way to block tumor growth.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose of vorinostat in combination with trastuzumab (Herceptin) in patients with metastatic or local chest wall recurrent HER-2-amplified breast cancer. (Phase I) II. To determine the toxic effects of this regimen in these patients. (Phase I) III. To determine the response rate in patients treated with this regimen. (Phase II)
SECONDARY OBJECTIVE:
I. To determine the time to progression in patients treated with this regimen. (Phase II)
OUTLINE: This is an open-label, multicenter, dose-escalation study of vorinostat.
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
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No active or ongoing infection
- •No history of allergic reaction to compounds of similar chemical or biologic composition to vorinostat or other agents used in study
- •No psychiatric illness or social situation that would preclude study compliance
- •No other uncontrolled illness
- •More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin; 1 week for capecitabine) and recovered
- •More than 3 weeks since prior radiotherapy and recovered
- •Recovered from prior therapy
- •At least 2 weeks since prior valproic acid
- •More than 4 weeks since prior investigational agents
- •More than 4 weeks since prior lapatinib ditosylate
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •Measurable disease, defined as >= 1 unidimensionally measurable lesion > 20 mm by conventional techniques or > 10 mm by spiral CT scan
- •No other concurrent investigational agents
- •Concurrent bisphosphonates allowed provided therapy was initiated prior to study treatment
- •No other concurrent anticancer therapy
- •Recurrent or progressive disease while receiving prior trastuzumab (Herceptin) (with or without chemotherapy) OR relapsed within 3 months of last dose of prior adjuvant trastuzumab for metastatic disease
- •Histologically confirmed breast cancer
- •Must overexpress HER-2 gene
- •Metastatic or chest wall recurrent disease
- •Site of measurable disease must not have been irradiated (except chest wall recurrence treated with adjuvant radiation therapy)
- •No untreated brain metastases
- •Previously treated brain metastasis responsive to radiotherapy and/or surgery allowed provided the brain is not the sole site of measurable disease
- •Absolute neutrophil count >= 1,500/mm^3
- •Platelet count >= 100,000/mm^3
- •Hemoglobin >= 9 g/dL
- •AST and ALT =< 2 times upper limit of normal
- •Bilirubin =< 1.5 mg/dL (3 mg/dL in the presence of Gilbert's disease provided direct bilirubin is normal)
- •Creatinine =< 1.5 mg/dL
- •LVEF normal by nuclear scan or echocardiogram
- •No evidence of PR prolongation or AV block by EKG
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients will receive vorinostat by mouth twice a day for 2 weeks. They will also receive a 90-minute infusion of trastuzumab in week 1.
干预措施: vorinostat (Drug)
Arm I
Patients will receive vorinostat by mouth twice a day for 2 weeks. They will also receive a 90-minute infusion of trastuzumab in week 1.
干预措施: trastuzumab (Drug)
结局指标
主要结局
Response Rate
时间窗: Tumor assessment was obtained at baseline, after 6 weeks (week 6 = last week of Cycle 2), and after every 4 cycles of therapy
Tumor response is assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0. Response included complete response (CR) and partial response (PR). CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter.
次要结局
- Time to Progression(Tumor assessment was obtained at baseline, after 6 weeks (week 6 = last week of Cycle 2), and after every 4 cycles of therapy)
- Overall Survival(Survival was assessed every 3 months for first 2 years from protocol entry, then every 6 months until 3 years from study entry)