A Phase I and a Randomized Phase II Study of Maximal Angiogenic Blockade in Advanced Renal Carcinoma: Bevacizumab (NSC-704865) With or Without MEDI-522 (NSC-719850)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 5
- 主要终点
- Maximum Tolerated Dose of Bevacizumab , Based on Incidence of Dose-limiting Toxicity (DLT) Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Phase I)
研究概览
简要总结
This phase I/randomized phase II trial is studying the side effects and best dose of bevacizumab and to see how well it works when given together with or without MEDI-522 in treating patients with unresectable or metastatic kidney cancer. Monoclonal antibodies, such as bevacizumab and MEDI-522, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab and MEDI-522 may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether bevacizumab is more effective when given together with or without MEDI-522 in treating kidney cancer.
详细描述
PRIMARY OBJECTIVES:
I. To assess the appropriate dose of bevacizumab when administered with humanized monoclonal antibody MEDI-522 in patients with unresectable or metastatic renal cell carcinoma previously treated with sunitinib malate or sorafenib tosylate. (Phase I) II. To compare the progression-free survival of these patients treated with bevacizumab with versus without humanized monoclonal antibody MEDI-522. (Phase II) III. To evaluate the qualitative and quantitative toxicities of bevacizumab and humanized monoclonal antibody MEDI-522 in these patients. (Phase II) IV. To estimate overall survival and RECIST response rate (i.e., confirmed and unconfirmed, complete and partial responses) in both treatment arms. (Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study of bevacizumab followed by a randomized phase II study.
PHASE I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and humanized monoclonal antibody MEDI-522 IV on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity until the recommended phase II dose (RPTD) of bevacizumab is determined.
PHASE II: Patients are stratified according to the number of prior treatment regimens for renal cell carcinoma (1 vs 2) and whether there is a clear cell component (yes vs no). Patients are randomized to 1 of 2 treatment arms:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Phase II Arm I
Patients receive bevacizumab (10mg/kg) IV over 30-90 minutes on days 1 and 15.
干预措施: bevacizumab (Biological)
Phase II Arm II
Patients receive bevacizumab IV as in arm I at the RPTD determined in phase I, and humanized monoclonal antibody MEDI-522 (8mg/kg) IV over 30 minutes on days 1, 8, 15, and 22.
干预措施: etaracizumab (Drug)
Phase II Arm II
Patients receive bevacizumab IV as in arm I at the RPTD determined in phase I, and humanized monoclonal antibody MEDI-522 (8mg/kg) IV over 30 minutes on days 1, 8, 15, and 22.
干预措施: bevacizumab (Biological)
结局指标
主要结局
Maximum Tolerated Dose of Bevacizumab , Based on Incidence of Dose-limiting Toxicity (DLT) Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Phase I)
时间窗: Up to 8 weeks
Progression-free Survival (Phase II)
时间窗: From date of registration to date of first observation of progressive disease, systemic deterioration, or death due to any cause, assessed up to 3 years
Measured from date of registration to date of first observation of progressive disease, symptomatic deterioration or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact.
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug, Graded According to NCI CTCAE Version 3.0 (Phase II)
时间窗: Up to 3 years
Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST), Including Confirmed and Unconfirmed Complete and Partial Responses (Phase II)
时间窗: Up to 3 years
Complete Response (CR) is a complete disappearance of all measurable and non-measurable disease. No new lesions. No disease related symptoms. Partial Response (PR) applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of nonmeasurable disease. No new lesions.
Overall Survival (Phase II)
时间窗: From date of registration to date of death due to any cause, assessed up to 3 years
Measure from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
次要结局
- Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug(Patients were assessed for the first 8 weeks for dose-limiting toxicities, then assessed for adverse events after every cycle (1 cycle = 28 days) of protocol treatment, up to 3 years)