Molecular Markers in Predicting Response to Treatment in FH-deficient RCC Patients
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Patients with FH-deficient RCC Laboratory analysis of samples |
Other: Laboratory analysis of samples
Laboratory analysis of samples
|
Outcome Measures
Primary Outcome Measures
- Systemic treatment OS [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.
Secondary Outcome Measures
- First-line PFS [Through study completion, an average of 3 year]
First-line progression free survival (PFS) was defined as the time from the start of first-line systemic treatment to the time of radiographic progression, or death from any cause, whichever occurred first.
- ORR [Through study completion, an average of 3 year]
Objective response rate (ORR) was defined as complete response (CR)+ partial response (PR)
- DCR [Through study completion, an average of 3 year]
disease control rate (DCR) was defined as partial response (PR)+complete response (CR)+stable disease (SD)
Eligibility Criteria
Criteria
Inclusion Criteria:
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≥18 years old;
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histopathological evidence of FH-deficient RCC, which was confirmed by Sanger or next-generation sequencing after initial screening by IHC.
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included patients must be diagnosed with metastatic renal cell carcinoma or have a TNM stage IV (according to 2009 TNM Classification);
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new FH-deficient RCC patients who has scheduled to start 1st cycle of systemic treatment;
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ECOG score ≤2;
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life expectancy ≥ 3 months;
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sign informed consent, and be able to follow the visit and related procedures stipulated in the program;
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agree to collect tumor tissue, blood and other specimens required by this study and apply them to relevant studies;
Exclusion Criteria:
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patients with other malignant tumors with different primary sites or histology from the tumor evaluated in this study within 2 years of personal history.
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major surgery or severe trauma within 4 weeks before enrollment;
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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.
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known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
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allergic to any component of monoclonal antibody;
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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.;
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class iii-iv congestive heart failure (New York heart association classification), poorly controlled and clinically significant arrhythmia;
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uncontrolled arterial hypertension (systolic blood pressure ≥160mmHg or diastolic blood pressure ≥100mmHg);
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pregnant or lactating women.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ethics Committee of Shanghai Renji Hospital | Shanghai | Shanghai | China |
Sponsors and Collaborators
- RenJi Hospital
- Tongji Hospital
- Changzhou No.2 People's Hospital
- Ruijin Hospital
- Second Affiliated Hospital, School of Medicine, Zhejiang University
- Shanghai 10th People's Hospital
- First Affiliated Hospital of Fujian Medical University
- Shanghai Zhongshan Hospital
- Jiangxi Provincial People's Hopital
- First Affiliated Hospital, Sun Yat-Sen University
- Zhejiang Provincial People's Hospital
- Peking University First Hospital
- Zhejiang University
- Fudan University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RENJIFHRCC