Multi-omics Analysis of Renal Cell Carcinoma Mechanisms; Drug Sensitivity Testing in Patient-Derived Cell-based Microtumors

NCT07351266 | Not Yet Recruiting

• 1 other identifier: NCC020381
• Study Type: observational
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a research study aiming to better understand a type of kidney cancer called Renal Cell Carcinoma (RCC). Doctors have observed that inside some larger RCC tumors, there are multiple smaller nodules. This study wants to find out if these nodules are different from each other and how they might be related. To do this, researchers will study tumor tissue samples from 10 patients with RCC who are having surgery. From each tumor, several nodules will be analyzed using advanced laboratory techniques. These techniques will create very detailed maps of the genes and cells within each nodule. At the same time, tiny 3D tumor models (called microtumors) will be grown from these samples in the lab to test how they respond to different cancer drugs. The main goal is to combine these two types of information to see how the differences in genes and cells between nodules might explain why some tumors stop responding to treatment (become resistant). We hope this study will lead to a deeper understanding of how RCC grows and spreads, and help find new ways to diagnose and treat it in the future.

Conditions

Renal Cell Carcinoma (Kidney Cancer)

Keywords

Multi-omics; Single-Cell Sequencing; Spatial Transcriptomics; Whole Exome Sequencing; Microtumors; Patient-Derived Cells; Drug Sensitivity Testing; Tumor Heterogeneity; Intratumoral Nodules

Outcome Measures

Primary Outcomes (1)

• Identification of Intra-tumoral Nodule Driving Relationships

  The primary outcome is the bioinformatic inference of potential clonal evolutionary "driver-subordinate" relationships between different intratumoral nodules within the same RCC tumor. This is determined by integrating multi-region single-cell RNA sequencing and whole-exome sequencing data. Key analyses include: 1) Comparative analysis of mutational landscapes and copy number variations across nodules to identify shared trunk mutations and private branch mutations. 2) Pseudotime trajectory analysis of single-cell data to reconstruct the potential temporal sequence of nodule emergence. A relationship will be inferred if a consistent pattern of shared ancestral mutations and/or a unidirectional differentiation trajectory is identified.

  Through study completion, an average of 16 months

Secondary Outcomes (2)

• Correlation between Ex Vivo Drug Sensitivity and Multi-omics Features

  Through study completion, an average of 24 months

• Characterization of Inter-nodular Heterogeneity at Single-Cell Resolution

  Through study completion, an average of 24 months

Study Arms (1)

Study Cohort

All enrolled participants undergo the same study procedures. This includes surgical resection of the renal cell carcinoma tumor, followed by multi-region sampling of intratumoral nodules for integrated multi-omics analysis (single-cell RNA sequencing, whole-exome sequencing, spatial transcriptomics) and the generation of patient-derived microtumor (PTC) models for ex vivo drug sensitivity testing.

Diagnostic Test: Multi-region Tumor Sampling and Integrated Multi-omics Analysis and Microtumor PTC Drug Sensitivity Assay

Interventions

Multi-region Tumor Sampling and Integrated Multi-omics Analysis and Microtumor PTC Drug Sensitivity Assay DIAGNOSTIC_TEST

This integrated intervention involves: 1) Multi-region sampling of intratumoral nodules from resected RCC tumors for multi-omics analysis (single-cell RNA-seq, whole-exome sequencing, spatial transcriptomics) to map molecular and cellular heterogeneity. 2) Parallel generation of patient-derived microtumor (PTC) models from the same nodules for ex vivo drug sensitivity testing against a panel of oncology agents (e.g., Axitinib, Pembrolizumab). The core purpose is to correlate molecular features from omics with functional drug response data to decipher mechanisms of intra-tumoral heterogeneity and resistance.

Study Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study plans to enroll 10 patients with locally advanced renal cell carcinoma. Participants must be newly diagnosed and treatment-naïve prior to surgery, with primary tumors ≥7 cm exhibiting a multinodular gross appearance, and scheduled to undergo radical nephrectomy.

You may qualify if:

• Histologically confirmed renal cell carcinoma with regional lymph node metastasis.
• Primary tumor with a maximum diameter ≥ 7 cm.
• Tumor exhibits a multinodular distribution pattern on cross-section (assessed via intraoperative or postoperative gross specimen).
• Age \> 18 years.
• Ability to understand the study and voluntarily provide written informed consent.

You may not qualify if:

• Presence of distant metastasis (M1 stage).
• Prior receipt of any targeted therapy or immunotherapy for renal cell carcinoma before surgery.
• History of other active malignancies besides RCC (except cured basal cell carcinoma of the skin or carcinoma in situ of the cervix).
• Any psychiatric, neurological, or legal condition that may compromise the ability to understand the informed consent or to comply with study procedures.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Central Study Contacts

Xiongjun Ye

CONTACT

8613910380916; yexiongjun@cicams.ac.cn

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: January 12, 2026
• First Posted: January 20, 2026
• Study Start: January 25, 2026
• Primary Completion (Estimated): January 25, 2028
• Study Completion (Estimated): January 25, 2030
• Last Updated: January 20, 2026

Record last verified: 2026-01