A Phase II Study of ZD6474 (Vandetanib) in Subjects With Advanced Clear Cell Renal Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Number of Participants With a Clinical Response (Partial Response (PR) + Clinical Response (CR))
研究概览
简要总结
Background:
- One way tumors are able to grow is by forming new blood vessels that supply it with nutrients and oxygen.
- Vandetanib (ZD6474) is an experimental drug that blocks certain proteins on the surface of tumor and blood vessel cells that are involved with the formation of new blood vessels.
- Blocking these proteins may prevent the tumor cells or blood vessels from continuing to grow.
Objectives:
- To determine whether vandetanib can cause tumors to shrink or stabilize in patients with advanced kidney cancer.
- To determine how vandetanib may work in people with kidney cancer and to develop tests that may be helpful in studying kidney cancer.
Eligibility:
-Patients 18 years of age or older with advanced clear cell kidney cancer whose disease has worsened after treatment with one or more of the following drugs: sunitinib, sorafenib, interleukin-2 and temsirolimus; or patients who have had to stop treatment with these drugs due to unacceptable side effects; or patients who are unable to receive standard treatment.
Design:
- Patients take a vandetanib pill once a day in 28-day cycles.
- Patients are followed in the clinic every 2 weeks during the first month of treatment and then every 4 weeks for a physical examination, blood and urine tests, electrocardiogram and a review of any drug side effects.
- Patients have imaging scans (computed tomography (CT) or magnetic resonance imaging (MRI)) about every 8 weeks to monitor tumor growth. MRI scans are also done to look at tumor blood flow when treatment begins, 24 hours after the first dose of treatment, and again about 4 and 8 weeks after starting treatment
- Optional tumor biopsies (surgical removal of a sample of tumor tissue) may be done before starting vandetanib treatment and after 4 weeks of treatment to look for drug effects on the tumor.
详细描述
Background:
- von Hippel-Lindau (VHL) inactivation by mutation or promoter hypermethylation is seen in a high proportion of sporadic clear cell renal cancers.
- Inactivation of VHL leads to accumulation of proteins targeted for degradation through the ubiquitin pathway, which includes a group of transcriptionally active proteins called the hypoxia inducible factors (HIF), whose alpha subunits undergo degradation in a VHL-dependent fashion.
- Accumulation of HIFs results in overexpression of several genes including vascular endothelial growth factor (VEGF), glucose transporter 1 (GLUT-1), transforming growth factor (TGF-a), platelet derived growth factor (PDGF), and erythropoietin, which are believed to play a role in tumorigenesis, tumor progression and metastasis.
- Kinase insert domain-containing receptor/vascular endothelial growth factor receptor 2 (kinase insert domain receptor (KDR)/vascular endothelial growth factor 2 (VEGFR2)) is an endothelial cell receptor for vascular endothelial growth factor (VEGF) and plays a crucial role in mediating tumor angiogenesis, while EGFR (a receptor for TGF-a and epidermal growth factor (EGF) is believed to mediate tumor growth and proliferation.
- ZD6474 is an orally administered receptor tyrosine kinase inhibitor with activity against the KDR/VEGFR2 and the epidermal growth factor receptor (EGFR).
Objective:
Primary Objective
-To evaluate the efficacy (overall response rate) of single agent ZD6474 in advanced clear cell renal cell carcinoma (RCC).
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Clear Cell Renal Carcinoma
Clear cell renal cancer is a highly vascular tumor characterized by mutations in the von Hippel-Lindau (VHL) gene in the majority of patients, an alteration that leads to overexpression vascular endothelial growth factor (VEGF) as well as other genes such as transforming growth factor-alpha, platelet derived growth factor and glucose transporter 1. Patients received ZD6474 300 mg/day by mouth daily on days 1-28.
干预措施: vandetanib (Drug)
结局指标
主要结局
Number of Participants With a Clinical Response (Partial Response (PR) + Clinical Response (CR))
时间窗: 12 months
Clinical response is the best response recorded from the start of treatment until disease progression. Clinical response is assessed by the Response Evaluation in Solid Tumors (RECIST) criteria. A partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD. A complete response (CR) is the disappearance of all target lesions.
次要结局
- Effect of Vandetanib on Plasma Biomarkers-vascular Endothelial Growth Factor (VEGF), Vascular Endothelial Growth Factor 2 (VEGFR2)(12 months)
- Progression-free Survival as Defined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria(12 months)
- Number of Participants With Adverse Events(11.5 months)
- Number of Circulating Endothelial Cells (CEC) Per 10^6 Mononuclear Cells or Per Microliter of Peripheral Blood Analyzed in Samples Taken Before and After Treatment(12 months)
- Number of Participants With Vandetanib (ZD6474) Effects on Tumor Vascular Flow and Permeability Using Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI)(12 months)
- Tumor Tissue Used to Evaluate Von Hippel-Lindau (VHL) Status and/or Components of the Vascular Endothelial Growth Factor (VEGF)/Epidermal Growth Factor Receptor (EGFR) Pathway(12 months)
- The Effects of ZD6474 (Vandetanib) on Tumor Microvessel Density(12 months)
- Evaluate The Correlation Between Von Hippel-Lindau (VHL) Mutational Status and Response to ZD6474 (Vandetanib)(12 months)
- Number of Circulating Endothelial Progenitor Cells (CEP) Per 10^6 Mononuclear Cells or Per Microliter of Peripheral Blood Analyzed in Samples Taken Before and After Treatment(12 months)
研究者
W. Marston Linehan, M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)