Overtaking Intra and Inter Tumoral Heterogeneity In Von Hippel-Lindau Related Renal Cancer
- Conditions
- VHL SyndromeClear Cell Renal Cell Carcinoma
- Interventions
- Other: Blood collection
- Registration Number
- NCT06195150
- Lead Sponsor
- IRCCS San Raffaele
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 3
- VHL syndrome
- Presence of at least 3 kidney tumors larger that 3cm to be surgically removed
- Absence of VHL
- Quantity of kidney tumors < 3
- Absence of surgery performance
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description VHL patients Blood collection 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.
- Primary Outcome Measures
Name Time Method Integrating Imaging and multiregion biopsy sampling in VHL related ccRCC From month 3 to month 20 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.
Determine immune and stromal heterogeneity in VHL-ccRCC 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. Multiplex immunohistochemistry, bulk and single cell RNA sequencing and somatic mutations analysis with pan-tumor histological assessment will be combined.
Generation and characterization of VHL-ccRCC patient-derived organoids From month 3 until the end of the project. 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
IRCCS Ospedale San Raffaele
🇮🇹Milan, MI, Italy