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

San Donato Group (GSD)

Status: Enrolling

Conditions: VHL Syndrome; Clear Cell Renal Cell Carcinoma

Treatments: Other: Blood collection

Study type: Observational

Funder types: Other

Identifiers

NCT06195150

PNRR-MR1-2022-12375818

Details and patient eligibility

About

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.

Full 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.

Enrollment: 3 estimated patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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

Trial design

3 participants in 1 patient group

VHL patients

Description:

Patients with hereditary Von Hippel-Lindau (VHL) with genetic diagnosis of VHL disease who have at least three tumors larger than 3cm that have to be surgically removed. The procedure involves standard surgery with the additional collection of 15ml of blood.

Treatment:

Other: Blood collection