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

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.

Study Overview

• Status: Recruiting
• Conditions: Biomarkers; FH-Deficient RCC; Systemic Treatments
• Intervention / Treatment: Other: Laboratory analysis of samples

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Yunze Xu; Phone Number: +8618801967501; Email: xuyunze@renji.com
• Study Contact Backup: Name: Jin Zhang; Email: zhangjin@renji.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Ethics Committee of Shanghai Renji Hospital
      • Contact: Qi Lu; Phone Number: +86021-68383364; Email: rjllb3364@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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

Description

Inclusion Criteria:

1. ≥18 years old;
2. histopathological evidence of FH-deficient RCC, which was confirmed by Sanger or next-generation sequencing after initial screening by IHC.
3. included patients must be diagnosed with metastatic renal cell carcinoma or have a TNM stage IV (according to 2009 TNM Classification);
4. new FH-deficient RCC patients who has scheduled to start 1st cycle of systemic treatment;
5. ECOG score ≤2;
6. life expectancy ≥ 3 months;
7. sign informed consent, and be able to follow the visit and related procedures stipulated in the program;
8. agree to collect tumor tissue, blood and other specimens required by this study and apply them to relevant studies;

Exclusion Criteria:

1. patients with other malignant tumors with different primary sites or histology from the tumor evaluated in this study within 2 years of personal history.
2. major surgery or severe trauma within 4 weeks before enrollment;
3. 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.
4. known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
5. allergic to any component of monoclonal antibody;
6. 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.;
7. class iii-iv congestive heart failure (New York heart association classification), poorly controlled and clinically significant arrhythmia;
8. uncontrolled arterial hypertension (systolic blood pressure ≥160mmHg or diastolic blood pressure ≥100mmHg);
9. pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with FH-deficient RCC; Laboratory analysis of samples	Other: Laboratory analysis of samples; Laboratory analysis of samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
First-line PFS	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.	Through study completion, an average of 3 year
ORR	Objective response rate (ORR) was defined as complete response (CR)+ partial response (PR)	Through study completion, an average of 3 year
DCR	disease control rate (DCR) was defined as partial response (PR)+complete response (CR)+stable disease (SD)	Through study completion, an average of 3 year

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: August 15, 2022
• First Submitted That Met QC Criteria: September 6, 2022
• First Posted (Actual): September 10, 2022

Study Record Updates

• Last Update Posted (Actual): August 31, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: RENJIFHRCC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No