A Randomized Phase II Trial of Vandetanib (ZD6474) in Combination With Carboplatin Versus Carboplatin Alone Followed by Vandetanib Alone in Adults With Recurrent High-Grade Gliomas
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 112
- 试验地点
- 1
- 主要终点
- Progression Free Survival at 6 Months
研究概览
简要总结
Background:
- Growth of new blood vessels (angiogenesis) provides many tumors, including brain tumors, with needed nutrients and oxygen for cancer cells to survive. One possible treatment for different kinds of cancer involves treatment with drugs that slow or stop angiogenesis and prevent further tumor growth.
- Vandetanib is an oral medication known to block angiogenesis and has shown significant antitumor activity in laboratory and animal studies. Vandetanib appears to be well tolerated by patients at specific daily doses.
- Carboplatin is a drug that interrupts division of cancer cells and has been shown to be a useful drug in treatment of tumors known as gliomas. It is a useful drug for treating brain tumors, but researchers are interested in gathering more information about how it works as a treatment for patients who have not responded to initial surgery, radiation, or chemotherapy.
Objective:
- To determine the safety and effectiveness of vandetanib and carboplatin, given together or sequentially, against recurrent high-grade gliomas.
Eligibility:
- Adults diagnosed with a malignant glioma who have received standard treatments that no longer appear to be effective.
Design:
- Patients will be assigned to one of two groups. Group 1 patients (combination group) will receive oral vandetanib for 28 days and intravenous (IV) carboplatin (once at the beginning of the 28-day cycle). Group 2 patients (sequential group) will receive IV carboplatin alone (once at the beginning of the 28-day cycle) and then oral vandetanib (300 mg daily) for 28 days if the tumor grows or the patient develops unacceptable carboplatin toxicity.
- Treatment will continue in 28-day cycles for 1 year for both groups.
- Patients will undergo a number of tests and procedures during the treatment cycle, including physical examinations, routine laboratory tests, electrocardiograms, and magnetic resonance imaging (MRI) scans
- At the end of 1 year of treatment, patients will be reevaluated for possible continuation of drug therapy.
详细描述
Background:
In vivo experiments have documented the ability of vandetanib (ZD6474) to inhibit tumor growth in various preclinical tumor models. Given the pronounced neovasculature associated with malignant gliomas, and abundant published data demonstrating the dependence of glioma growth on the maintenance and proliferation of this neovasculature, vandetanib represents a potentially promising new therapeutic approach to these otherwise refractory tumors. Phase II data of vandetanib for recurrent glioblastomas conducted at the National Institutes of Health showed promising activity but responses were usually short-lasting.
Carboplatin has shown activity as monotherapy in the treatment of recurrent malignant gliomas in adults and preclinical data generated at Dr. Fines' laboratory demonstrate additive anti-glioma activity with vandetanib. The safety profile of carboplatin and the preclinical and clinical data supports its use in combination with vandetanib in patients with malignant gliomas.
Vandetanib is also an epidermal growth factor receptor (EGFR) inhibitor and it has been demonstrated that the presence of the EGFRvIII mutant and/or the presence of an intact phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and non-phosphorylated protein kinase B (AKT) predict for a higher likelihood of response to the EGFR inhibitors Tarceva and Iressa.
Objectives:
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
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 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
Group 1
Combo Group (both drugs together)
干预措施: ZD6474 (Vandetanib) (Drug)
Group 2
Sequential Group (carboplatin followed by vandetanib)
干预措施: ZD6474 (Vandetanib) (Drug)
Group 2
Sequential Group (carboplatin followed by vandetanib)
干预措施: Carboplatin (Drug)
Group 1
Combo Group (both drugs together)
干预措施: Carboplatin (Drug)
结局指标
主要结局
Progression Free Survival at 6 Months
时间窗: 6 months
Percentage of participants who are alive and progression-free at 6 months.
次要结局
- Overall Survival(Time between the first day of treatment and the day of death, up to 1.5 years)
- Number of Participants With Adverse Events(70 months and 19 days)
研究者
Katherine E. Warren, M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)