Molecular Markers in Predicting Response to Treatment in FH-deficient RCC Patients

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.

Conditions

• FH-Deficient RCC
• Systemic Treatments
• Biomarkers

Interventions

OTHER

Laboratory analysis of samples

Laboratory analysis of samples

Sponsors & Collaborators

• Tongji Hospital

  collaborator OTHER

• Changzhou No.2 People's Hospital

  collaborator OTHER

• Ruijin Hospital

  collaborator OTHER

• Second Affiliated Hospital, School of Medicine, Zhejiang University

  collaborator OTHER

• Shanghai 10th People's Hospital

  collaborator OTHER

• First Affiliated Hospital of Fujian Medical University

  collaborator OTHER

• Shanghai Zhongshan Hospital

  collaborator OTHER

• Jiangxi Provincial People's Hopital

  collaborator OTHER

• First Affiliated Hospital, Sun Yat-Sen University

  collaborator OTHER

• Zhejiang Provincial People's Hospital

  collaborator OTHER

• Peking University First Hospital

  collaborator OTHER

• Zhejiang University

  collaborator OTHER

• Fudan University

  collaborator OTHER

• RenJi Hospital

  lead OTHER

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-08-01

Primary Completion

2024-12-01

Completion

2024-12-01

Countries

• China

Study Locations