A Study of Biological, Pathological and Imagery Markers in the First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma With Sunitinib BEFORE and AFTER Nephrectomy
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- To evaluate the prognostic value of several factors (biomarkers and imaging) to identify responders
研究概览
简要总结
The aim of this study is to identify and/or validate biomarkers and imaging markers to predict and monitor the activity of a new class of therapeutic agents called antiangiogenics for the treatment of metastatic renal cell carcinoma (mRCC). Suntinib, approved for this indication, will be administred before and after nephrectomy and biomarkers sampling and imaging will be operated to monitor the activity and identify prognostic factors in mRCC.
详细描述
BACKGROUND Sunitinib, SUTENT, is a promising multi-target TKI in the treatment of metastatic renal cell carcinoma after cytokine failure. In previous phase II studies, ORR is 40% and TTP = 8,7 months. A phase III randomized trial of Sunitinib versus interferon alpha as first-line therapy for patients with mRCC showed a significantly longer PFS in the Sunitinib group (11 months) than in the interferon group (5 months), hazard ratio of 0.42 (95% CI, 0.32 to 0.54, p < 0.001). Initial approval in second line treatment of mRCC was extended to first line therapy on 11-01-2007.
Mechanisms of action involved in the therapeutic effects of antiangiogenic compounds are not fully elucidated. As of today, there are no validated biomarkers or imaging markers to predict and monitor the activity of this type of compound.
Recent findings in the field of cancer biology, tumor angiogenesis, immunology and imaging provide several biomarker candidates that can be assessed in metastatic renal cell carcinoma.
BASIC RESEARCH Biomarkers It seems interesting to measure the different biological markers that could be modulated by this antiangiogenic therapeutic. Some of them are known as prognostic factors in the metastatic renal carcinoma, others are directly linked to the mechanism of action of Sunitinib. Due to the biopsy prior to treatment initiation and nephrectomy after treatment initiation, it will be possible to evaluate biomarkers modification and to assess the potential link with the tumour response.
VHL gene alterations (mutations, deletions, and hypermethylations) are observed at high frequencies of up to 80% in cases of clear-cell renal cell carcinoma. The molecular mechanisms involved in angiogenesis in the presence of such genetic alterations are not yet well known. The functions of the pVHL/aHIF/VEGF/angiogenesis pathway will be investigated in all the renal cell carcinoma obtained from the biopsy and nephrectomy. Molecular markers defined by VHL status, expression and proteomic profiling may be helpful in predicting the responders.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
SUTENT before nephrectomy
干预措施: Sunitinib (SUTENT) (Drug)
结局指标
主要结局
To evaluate the prognostic value of several factors (biomarkers and imaging) to identify responders
时间窗: 36 weeks
次要结局
- To determine the objective response rate after initiation of treatment in the primitive tumour, according to the RECIST criteria.(12 weeks)
- To assess the pathological response (tumoral extension), Progression Free Survival (PFS) as defined by pProgression Free Survival (PFS) as defined by progression of metastasis, overall survival (OS).(24 months)
- To evaluate the correlation between tumor extension as defined by the pathologist and the tumor reduction between initiation of treatment and nephrectomy as measured by CT scan(12 weeks)
- To evaluate the correlation between the imaging obtained with Dynamic Contrast-enhanced CT scan, with contrast-enhanced US and VEGF expression(6 weeks)
- To explore the pharmacokinetic of Sunitinib at study state(4 weeks)
- To compare marker expression in the biopsy (before treatment) and in the primitive tumor.(12 weeks)
- To evaluate the ability of investigated biomarkers and VEGF-A gene polymorphisms to be prognostic of the pathological response and of the Progression Free Survival.(24 months)
- To monitor the potential renal toxicity of Sunitinib(24 months)