Overtaking Intra and Inter Tumoral Heterogeneity In Von Hippel-Lindau Related Renal Cancer

Clear Cell Renal Cell Carcinoma Clinical Trial

— ITHORinVHL  

Official title:

Overtaking Intra and Inter Tumoral Heterogeneity In Von Hippel-Lindau Related Renal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06195150
• Other study ID #: PNRR-MR1-2022-12375818
• Status: Recruiting
• Start date: November 8, 2023
• Est. completion date: August 31, 2024

Study information

• Verified date: March 2024
• Source: IRCCS San Raffaele
• Contact: Umberto Capitanio, MD
• Phone: 3492503788
• Email: capitanio.umberto[@]hsr.it
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The goal of this study is to comprehensively map intra and inter tumor heterogeneity of ccRCC in VHL patients through the use of imaging, molecular biology and genomics techniques.

Description:

It was hypothesized that the high intra- inter-tumor heterogeneity of sporadic ccRCC also defines VHL-ccRCCs, including different lesions within individual patients, and it was assumed that decoding VHL-ccRCC heterogeneity by coupling imaging, histology and molecular profiling of multiregional biopsies would help improve diagnostic tests and therapeutic choices for VHL patients.

In order to comprehensively map intra and inter tumor heterogeneity of ccRCC in VHL patients, the aims of the study are:

1. To integrate pre-surgery imaging using conventional multiparametric MRI with tumor histology of geographical predeterminated multi-region biopsies in each ccRCC of VHL patients.

2. To combine multiplex immunohistochemistry, bulk and single cell RNA sequencing and somatic mutations analysis with pan-tumor histological assessment.

3. To optimize a protocol to generate VHL-ccRCC-derived tumor organoids (patient-derived organoids, PDO) and test anti tumor agents like HIF2alpha inhibitor in organoid cultures representative of intra- and inter-tumor heterogeneity.

This study will develop standardized models for diagnosis and molecular characterization of ccRCC in VHL disease using a combination of imaging, intrasurgical biopsying and multi-omics analysis. It will benefit of a clinical and research program devoted to VHL disease established at OSR in 2021 that centralizes Italian VHL patients. Since the current study relies on tumor biopsy techniques that are already established in clinical practice, the translational findings will be directly available and immediately affecting patients' care.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3
• Est. completion date: August 31, 2024
• Est. primary completion date: August 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• VHL syndrome

• Presence of at least 3 kidney tumors larger that 3cm to be surgically removed

Exclusion Criteria:

• Absence of VHL

• Quantity of kidney tumors < 3

• Absence of surgery performance

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Clear Cell Renal Cell Carcinoma
• Kidney Neoplasms
• VHL Syndrome
• Von Hippel-Lindau Disease

Intervention

Other:
• Blood collection
15ml of blood are harvested before surgery

Locations

Country	Name	City	State
Italy	IRCCS Ospedale San Raffaele	Milan	MI

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS San Raffaele

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Integrating Imaging and multiregion biopsy sampling in VHL related ccRCC	Pre-surgery imaging will be integrated using conventional multiparametric MRI with tumor histology of geographical predeterminated multi-region biopsies in each ccRCC of VHL patients.	From month 3 to month 20
Primary	Determine immune and stromal heterogeneity in VHL-ccRCC	Multiplex immunohistochemistry, bulk and single cell RNA sequencing and somatic mutations analysis with pan-tumor histological assessment will be combined.	DNAseq and bulk RNAseq will be carried out from month 7 until month 20. Multiplex immunohistochemistry (IHC) in multiregional biopsies and standard IHC on the whole tumors will be performed the last 12 months of the study.
Primary	Generation and characterization of VHL-ccRCC patient-derived organoids	A protocol to generate VHL-ccRCC-derived tumor organoids (patient-derived organoids, PDO) will be optimized to test anti tumor agents like HIF2alpha inhibitor in organoid cultures representative of intra- and inter-tumor heterogeneity.	From month 3 until the end of the project.