Clinical trial NCT06195150: Overtaking Intra and Inter Tumoral Heterogeneity In Von Hippel-Lindau Related Renal Cancer
Official title: Overtaking Intra and Inter Tumoral Heterogeneity In Von Hippel-Lindau Related Renal Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Clear Cell Renal Cell Carcinoma
VHL Syndrome
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
First posted: 2024-01-08
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: VHL patients with at least 3 kidney tumors larger that 3cm to be surgically removed

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Integrating Imaging and multiregion biopsy sampling in VHL related ccRCC
timeFrame: From month 3 to month 20
measure: Determine immune and stromal heterogeneity in VHL-ccRCC
timeFrame: 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.
measure: Generation and characterization of VHL-ccRCC patient-derived organoids
timeFrame: From month 3 until the end of the project.
Secondary outcomes:
Other outcomes:
Locations:
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele
state: MI
Study officials:
References: