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

Recruiting

• Conditions: Biomarkers; FH-Deficient RCC; Systemic Treatments
• Interventions: Other: Laboratory analysis of samples

• Registration Number: NCT05535829
• Lead Sponsor: RenJi Hospital

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-08-01
• Study First Submitted: 2022-08-15
• Study First Submitted QC: 2022-09-06
• Study First Posted: 2022-09-10
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-29
• Last Update Posted: 2023-08-31
• Primary Completion: 2024-12-01
• Study Completion: 2024-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with FH-deficient RCC	Laboratory analysis of samples	Laboratory analysis of samples

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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)

Trial Locations

Locations (1)

Ethics Committee of Shanghai Renji Hospital; 🇨🇳 Shanghai, Shanghai, China