Biomarkers of Response to Systemic Treatments in FH-deficient RCC
Renji Hospital, School of Medicine, Shanghai Jiao Tong University
Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare subtype of RCC characterized by germline/somatic mutation of the fumarate hydratase (FH) gene, and is an extremely aggressive tumor, with a propensity to disseminate early even in the setting of a small primary tumor.
Affected individuals or individuals suspected of having a germline FH will undergo periodic clinical assessment and genetic analyses for the purpose of: 1) definition and characterization of phenotype, 2) determination of the natural history of the disorder, and 3) genotype/phenotype correlation. Genetic linkage studies may be performed in situations in which the genetic basis of the disorder has not been elucidated.
研究概览
详细说明
- Discovery and validation of biomarker predicting FH-deficient RCC systemic treatments response
- Analysis for expression level of ctDNA using Next generation sequencing in FH-deficient RCC blood by systemic treatments response
- Analysis for expression level of mRNA using Next generation sequencing in FH-deficient RCC tissue by systemic treatments response
- Analysis for expression level of small molecule metabolites using mass spectrometry in FH-deficient RCC tissue and blood by systemic treatments response
- Analysis for genetic and protein expression at a single-cell level using a novel flow cytometry and RNA-sequencing protocol in FH-deficient RCC tissue and blood.
- Validation of genetic and protein expression using qRT-PCR or IHC in multiple independent cohort.
- Biological biomarkers-clinical factor combined prediction model of FH-deficient RCC systemic treatments response
研究类型
注册 (预期的)
联系人和位置
学习地点
-
-
-
Shanghai、中国、200127
- 招聘中
- Yunze Xu
-
接触:
- Yunze Xu
- 电话号码:+8618801967501
- 邮箱:rjxuyunze@163.com
-
-
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
取样方法
研究人群
描述
Inclusion Criteria:
- ≥18 years old;
- histopathological evidence of FH-deficient renal cell carcinoma, which was confirmed by Sanger or next-generation sequencing after initial screening by IHC.
- included patients must be diagnosed with metastatic renal cell carcinoma or have a TNM stage IV (according to 2009 TNM Classification);
- new FH-RCC patients who has scheduled to start 1st cycle of systemic treatment;
- ECOG score ≤2;
- life expectancy ≥ 3 months;
- sign informed consent, and be able to follow the visit and related procedures stipulated in the program;
- agree to collect tumor tissue, blood and other specimens required by this study and apply them to relevant studies;
- Patients must have consent in place, for the use of tissue and imaging to be used for the purposes of clinical research; Use of tissue not required for their diagnosis or treatment to be stored and used for the purposes of clinical research, which may include genetic research. Use of relevant sections of their medical records, or by relevant regulatory authorities, where my tissue is being used for research, giving permission for those individuals to have access to their medical records. Participants must also meet at least one of the following criteria to be eligible: For tissue analysis: Patient must have tumour tissue and/or normal adjacent kidney stored (either as formalinfixed paraffin-embedded tissue, or as 'fresh frozen' tissue). For imaging analysis: Patient must have had at least 1 scan (either CT or MRI) within 28 days of starting treatment with systemic treatment for their cancer.
Exclusion Criteria:
- patients with other malignant tumors with different primary sites or histology from the tumor evaluated in this study within 2 years of personal history, except those with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or cervical carcinoma in situ under good control;
- major surgery or severe trauma within 4 weeks before enrollment;
- known or suspected active autoimmune diseases (congenital or acquired), such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, thyroiditis, etc. Patients with type 1 diabetes with good insulin control can also be enrolled.
- known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
- allergic to any component of monoclonal antibody;
- suffering from other uncontrolled serious diseases, including but not limited to: A) severe infection in the active phase or clinically poorly controlled; B) HIV infection (HIV antibody positive); C) acute or chronic active hepatitis b (HBsAg positive and HBV DNA>1*103/ml) or acute or chronic active hepatitis c (HCV antibody positive and HCV RNA>15IU/ml); D) active tuberculosis, etc.;
- class iii-iv congestive heart failure (New York heart association classification), poorly controlled and clinically significant arrhythmia;
- uncontrolled arterial hypertension (systolic blood pressure ≥160mmHg or diastolic blood pressure ≥100mmHg);
pregnant or lactating women.
-
学习计划
研究是如何设计的?
设计细节
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 |
|---|---|---|
|
Metabolomics
大体时间:2 years
|
across multiple LC-MS data files.
across multiple LC-MS data files.
across multiple LC-MS data files.
across multiple LC-MS data files.
across multiple LC-MS data files
|
2 years
|
|
Determine genotype/phenotype correlations
大体时间:3 years
|
Collection of blood, tissue & urine to address further scientific questions related to this protocol.
|
3 years
|
|
Discovery of predicting bio-markers for FH-deficient RCC systemic treatments response
大体时间:3 years
|
Combination prediction model of biologic biomarkers and clinical factors for the response of systemic treatments in FH-RCC.
|
3 years
|
合作者和调查者
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (预期的)
研究完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.