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

NCT05535829 | Unknown

• 1 other identifier: RENJIFHRCC
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

FH-Deficient RCC; Systemic Treatments; Biomarkers

Outcome Measures

Primary Outcomes (1)

• Systemic treatment OS

  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.

  Through study completion, an average of 3 year

Secondary Outcomes (3)

• 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

Study Arms (1)

Patients with FH-deficient RCC

Laboratory analysis of samples

Other: Laboratory analysis of samples

Interventions

Laboratory analysis of samples OTHER

Laboratory analysis of samples

Patients with FH-deficient RCC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with advanced FH-deficient RCC who have given prior consent for their samples and data to be used, and who have received immunotherapy-based treatment

You may qualify if:

• ≥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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• RenJi Hospital: lead
• Tongji Hospital: collaborator
• Changzhou No.2 People's Hospital: collaborator
• Ruijin Hospital: collaborator
• Second Affiliated Hospital, School of Medicine, Zhejiang University: collaborator
• Shanghai 10th People's Hospital: collaborator
• First Affiliated Hospital of Fujian Medical University: collaborator
• Shanghai Zhongshan Hospital: collaborator
• Jiangxi Provincial People's Hopital: collaborator
• First Affiliated Hospital, Sun Yat-Sen University: collaborator
• Zhejiang Provincial People's Hospital: collaborator
• Peking University First Hospital: collaborator
• Zhejiang University: collaborator
• Fudan University: collaborator

Study Sites (1)

Ethics Committee of Shanghai Renji Hospital

Shanghai, Shanghai Municipality, China

RECRUITING

Central Study Contacts

Yunze Xu

CONTACT

+8618801967501; xuyunze@renji.com

Jin Zhang

CONTACT

zhangjin@renji.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2022
• First Posted: September 10, 2022
• Study Start: August 1, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: August 31, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)