Molecular Markers in Predicting Response to Treatment in FH-deficient RCC Patients
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Systemic treatment OS
研究概览
简要总结
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. This project is a real-world exploratory study aiming to explore potential molecular markers detectable at baseline that can enable the prediction of clinical efficacy of systemic treatments in advanced FH-deficient RCC.
This project is a real-world exploratory study aiming to explore potential molecular markers detectable at baseline that can enable the prediction of clinical efficacy of immunotherapy combined with target therapy in advanced FH-deficient RCC.
This study aims to include a total of 100 patients initially diagnosed with advanced FH-deficient RCC. Paired tissue and blood samples collected from all patients before or/ and after the start of immunotherapy-based treatment (at diagnosis or/ and their change with treatment) will be analyzed.
The patient samples will be submitted for molecular analysis, including next-generation sequencing (NGS)-based gene expression profiling (GEP), RNA-sequencing, multiplex immunofluorescence staining and inflammation-related T-cell receptor (TCR) repertoire profiling, ect. The molecular assay results will include but will not be limited to tumor mutation burden (TMB), microsatellite instability (MSI) status, DNA damage repair (DDR)-related gene mutation status, and programmed death-ligand 1 (PD-L1) expression level. Patients will be followed-up for treatment responses until radiological confirmation of disease progression to immunotherapy-based treatment. The molecular assay results will then be analyzed with clinical data including objective responses and progression-free survival outcomes, among others, to identify molecular markers at baseline that are associated with clinical efficacy of immunotherapy-based treatment.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
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
- •≥18 years old;
- •histopathological evidence of FH-deficient RCC, 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-deficient 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;
排除标准
- •patients with other malignant tumors with different primary sites or histology from the tumor evaluated in this study within 2 years of personal history.
- •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.
结局指标
主要结局
Systemic treatment OS
时间窗: Through study completion, an average of 3 year
Systemic treatment OS was defined as the time from the start of systemic treatment to death from any cause, and patients without a recorded death were right censored to the date of last clinical visit or clinical record.
次要结局
- First-line PFS(Through study completion, an average of 3 year)
- ORR(Through study completion, an average of 3 year)
- DCR(Through study completion, an average of 3 year)