Vorinostat and Bevacizumab in Treating Patients With Unresectable or Metastatic Kidney Cancer
Phase I/II Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With the VEGF Inhibitor Bevacizumab in Patients With Metastatic Renal Cell Carcinoma
研究概览
详细说明
PRIMARY OBJECTIVES:
I. Determine the safety and tolerability of vorinostat (SAHA) in combination with bevacizumab in patients with unresectable or metastatic renal cell carcinoma. (Phase I) II. Determine the recommended dosing in patients treated with this regimen. (Phase I) III. Determine the proportion of patients who are progression-free at 6 months after receiving this regimen. (Phase II) IV. Determine the clinical response rate in patients treated with this regimen. (Phase II)
SECONDARY OBJECTIVES:
I. Determine the toxicity of this regimen in these patients. (Phase II) II. Determine time to progression and duration of progression-free and overall survival in patients treated with this regimen. (Phase II) III. Determine the pharmacodynamic effects in peripheral blood mononuclear cells and tumors before and after treatment with this regimen in these patients. (Phase II) IV. Determine the antiproliferative and apoptotic effects of this regimen in these patients. (Phase II) V. Determine the antiangiogenic effects of this regimen in these patients. (Phase II) VI. Determine the modulation of tumor metabolism and tumor blood flow in patients treated with this regimen. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of vorinostat (SAHA) followed by a phase II study.
PHASE I: Patients receive oral SAHA twice daily on days 1-14 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients are treated at the MTD.
PHASE II: Patients receive SAHA at the MTD determined in phase I and bevacizumab as in phase I.
After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter.
研究类型
注册 (实际的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习地点
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Maryland
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Baltimore、Maryland、美国、21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
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Salisbury、Maryland、美国、21801
- Peninsula Oncology and Hematology PA
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Wisconsin
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Madison、Wisconsin、美国、53792
- University of Wisconsin Hospital and Clinics
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- No known CNS metastasis
- ECOG performance status 0-2
- Life expectancy > 6 months
- LVEF ≥ 45%
- Absolute neutrophil count ≥ 1,500/mm3
- Platelet count ≥ 100,000/mm3
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST/ALT ≤ 2.5 times ULN
- Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min
- PT/INR ≤ 1.5
- Urine protein < 1+ by urinalysis OR < 1 g by 24-hour urine collection
- Not pregnant
- No nursing during and for 6 months after completion of study treatment
- Negative pregnancy test
- Fertile patients must use effective contraception for 2 weeks prior, during, and for 6 months after completion of study treatment
- No other currently active malignancy defined as > 30% risk of relapse upon completion of anticancer therapy, except nonmelanoma skin cancer
- No history of allergic reaction attributed to compounds of similar chemical or biologic composition to vorinostat (SAHA)
- No hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- No evidence of bleeding diathesis or coagulopathy
- No active bleeding or pathological conditions that carry high risk of bleeding (i.e., tumor involving major vessels or known varices)
- No ongoing, active infection
- No New York Heart Association class II-IV congestive heart failure
- No angina pectoris requiring nitrate therapy
- No cardiac arrhythmia
- No myocardial infarction within the past 6 months
- No history of cerebrovascular accident within the past 6 months
- No uncontrolled hypertension (defined as systolic blood pressure (BP) > 160 mm Hg and/or diastolic BP > 90 mm Hg on medication)
- No history of peripheral vascular disease
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness
- No serious nonhealing wound, ulcer, or bone fracture
- No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
- No significant traumatic injury in the past 28 days
- At least 4 weeks since prior major surgery or open biopsy
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- More than 4 weeks since prior radiotherapy
- At least 2 weeks since prior tyrosine kinase inhibitor
- Prior palliative radiotherapy to metastatic lesions allowed provided ≥ 1 measurable and/or evaluable lesion has not been irradiated
- No more than 2 prior systemic treatments for metastatic disease, including immunotherapy, receptor tyrosine kinase inhibitor therapy, chemotherapy, or investigational therapy
- No prior therapy with bevacizumab, vascular endothelial growth factor-trap, or histone deacetylase inhibitors, including valproic acid
- No core biopsy within 1 week prior to day 1 of study treatment
- No planned major surgery during study treatment
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent investigational agents
- Concurrent stable-dose prophylactic anticoagulation (i.e., warfarin or low molecular weight heparin) allowed provided requirements for INR are met
- Histologically confirmed renal cell carcinoma, clear cell component, unresectable or metastatic disease (patients with a primary tumor in place who are eligible for surgery are strongly encouraged to undergo a nephrectomy prior to study entry to increase potential survival)
- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm with spiral CT scan
The following histologies are not allowed:
- Papillary, sarcomatoid carcinoma
- Chromophobe carcinoma
- Oncocytoma
- Collecting duct tumor
- Transitional cell carcinoma
- WBC ≥ 3,000/mm^3
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
实验性的:Arm I
Phase I: Patients receive oral SAHA twice daily on days 1-14 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients are treated at the MTD. Phase II: Patients receive SAHA at the MTD determined in phase I and bevacizumab as in phase I. |
口头给予
其他名称:
鉴于IV
其他名称:
|
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Progression-free Survival Assessed by Response Evaluation Criteria for Solid Tumors (RECIST) (Phase II)
大体时间:At 6 months
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Estimated by Kaplan-Meier method
|
At 6 months
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其他结果措施
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Maximum Tolerated Dose
大体时间:18 months from first patient dosing
|
Determine the maximum tolerated dose of SAHA
|
18 months from first patient dosing
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Clinical Response Rate of SAHA and Bevacizumab
大体时间:7 years
|
To determine the clinical response rate of SAHA and Bevacizumab in patients with metastatic renal cell carcinoma.
|
7 years
|
合作者和调查者
调查人员
- 首席研究员:Michael Carducci、Johns Hopkins University/Sidney Kimmel Cancer Center
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- NCI-2009-00093 (注册表标识符:CTRP (Clinical Trial Reporting Program))
- P30CA006973 (美国 NIH 拨款/合同)
- U01CA070095 (美国 NIH 拨款/合同)
- U01CA062491 (美国 NIH 拨款/合同)
- 6884 (其他标识符:CTEP)
- NA 00001107
- NCI-6884
- JHOC-J0570
- CDR0000467800
- JHOC-00001107
- J0570
- IRB #NA 00001107, SKCCC J0570 (其他标识符:Johns Hopkins University/Sidney Kimmel Cancer Center)
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伏立诺他的临床试验
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Samsung Medical Center未知