Renal Cell Carcinoma (Kidney Cancer)NCT07351266
Multi-omics Analysis of Renal Cell Carcinoma Mechanisms; Drug Sensitivity Testing in Patient-Derived Cell-based Microtumors
An observational study of Renal Cell Carcinoma (Kidney Cancer), run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma (Kidney Cancer)
- What is being tested?
- Multi-region Tumor Sampling and Integrated Multi-omics Analysis and Microtumor PTC Drug Sensitivity Assay
- How many people
- 10 participants
- Where
- No sites listed yet
- Study dates
- 25 Jan 2026to 25 Jan 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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.
Read the detailed description
Background and Rationale: Renal Cell Carcinoma (RCC) frequently exhibits intratumoral morphological heterogeneity, often presenting as distinct multiple nodules within a single tumor mass on cross-section. The biological and clinical significance of this multinodular architecture remains poorly understood. It is hypothesized that these nodules may represent clonal subpopulations with unique genomic, transcriptomic, and functional profiles, potentially driving tumor progression and therapy resistance. This study leverages integrated multi-omics and functional drug testing to systematically decipher the inter-nodular heterogeneity and evolutionary relationships within RCC.
Primary Objectives:
To delineate the cellular and genomic landscape of different intratumoral nodules in RCC using single-cell RNA sequencing (scRNA-seq), whole-exome sequencing (WES), and spatial transcriptomics.
To infer the potential clonal evolutionary relationships and driver-subordinate dynamics between coexisting nodules.
To characterize the differential drug sensitivity profiles of patient-derived microtumor (PTC) models established from distinct nodules.
To integrate multi-omics data with drug response data to explore underlying mechanisms of drug resistance.
Study Design and Methods: This is a single-center, prospective, basic science study. We will enroll 10 treatment-naïve patients with locally advanced RCC (tumor diameter ≥7 cm, with regional lymph node metastasis but no distant metastasis) scheduled for radical nephrectomy. Intraoperatively or immediately post-resection, each grossly multinodular tumor will be sectioned. Three dominant nodules (labeled T1, T2, T3 by size) will be identified from each specimen. From each nodule, four matched samples will be collected for: 1) scRNA-seq, 2) WES, 3) spatial transcriptomics, and 4) generation of 3D patient-derived tumor cell (PTC) microtumor models.
Analyses: Bioinformatic integration of scRNA-seq, WES, and spatial data will be performed to construct maps of cellular composition, genetic alterations, and their spatial distribution across nodules. Pseudotime trajectory analysis will be applied to infer potential evolutionary sequences. PTC models will undergo ex vivo drug sensitivity testing (e.g., against axitinib, pembrolizumab, and their combination). Differential response data will be correlated with omics-derived features (e.g., specific mutant alleles, cell subtype abundances, pathway activities) to identify candidate resistance mechanisms.
Significance: This is the first study to systematically investigate intratumoral nodular heterogeneity in RCC at a multi-omics level coupled with functional validation. Findings are expected to provide novel insights into RCC tumorigenesis and progression, potentially revealing new biomarkers for prognosis and therapeutic targets to overcome resistance.
- Conditions
- Renal Cell Carcinoma (Kidney Cancer)
- Being tested
- Multi-region Tumor Sampling and Integrated Multi-omics Analysis and Microtumor PTC Drug Sensitivity Assay
- Keywords
- Multi-omics, Single-Cell Sequencing, Spatial Transcriptomics, Whole Exome Sequencing, Microtumors, Patient-Derived Cells, Drug Sensitivity Testing, Tumor Heterogeneity, Intratumoral Nodules
- Medical subject headings
- Carcinoma, Renal Cell, Kidney Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multi-region Tumor Sampling and Integrated Multi-omics Analysis and Microtumor PTC Drug Sensitivity AssayDiagnostic 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 group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: Multi-region Tumor Sampling and Integrated Multi-omics Analysis and Microtumor PTC Drug Sensitivity Assay |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Through study completion, an average of 16 months
Secondary outcomes (2)
Correlation between Ex Vivo Drug Sensitivity and Multi-omics Features
This outcome measures the statistical correlation between the drug sensitivity profiles (e.g., IC50 values or cell viability percentages) of patient-derived microtumor (PTC) models from different nodules and specific molecular features derived from matched multi-omics data. Features include the abundance of specific cell subtypes (e.g., a malignant subpopulation), the expression level of a candidate gene, or the activity score of a signaling pathway (e.g., hypoxia, mTOR). Correlation will be assessed using methods such as Spearman's rank correlation or linear regression modeling.
Measured: Through study completion, an average of 24 months
Characterization of Inter-nodular Heterogeneity at Single-Cell Resolution
This outcome is a comprehensive description of the heterogeneity between intratumoral nodules, quantified by: 1) The number and identity of differentially abundant cell clusters (e.g., T cell subsets, macrophage states, malignant cell subtypes) between nodules, as defined by single-cell RNA-seq analysis. 2) The number of spatially variable genes or gene programs identified by spatial transcriptomics analysis that show distinct distribution patterns across nodules.
Measured: Through study completion, an average of 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2026
- Study start25 Jan 2026 (estimated)
- Primary completion25 Jan 2028 (estimated)
- Study completion25 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Cell Carcinoma (Kidney Cancer)Studies of the same condition, open and under way.
- More trials run by Cancer Institute and Hospital, Chinese Academy of Medical SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xiongjun Ye, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07351266
- Sponsor's protocol ID
- NCC020381
- Status last verified
- Jan 2026
- First submitted
- 12 Jan 2026
- Last updated
- 20 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-omics Analysis of Renal Cell Carcinoma Mechanisms; Drug Sensitivity Testing in Patient-Derived Cell-based Microtumors
- ClinicalTrials.gov ID
- NCT07351266
- Acronym / sponsor ID
- NCC020381
- 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
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical SciencesUniversity, hospital or other
- Study start
- 25 Jan 2026 (estimated)
- Primary completion
- 25 Jan 2028 (estimated)
- Study completion
- 25 Jan 2030 (estimated)
- First posted
- 20 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background and Rationale: Renal Cell Carcinoma (RCC) frequently exhibits intratumoral morphological heterogeneity, often presenting as distinct multiple nodules within a single tumor mass on cross-section. The biological and clinical significance of this multinodular architecture remains poorly understood. It is hypothesized that these nodules may represent clonal subpopulations with unique genomic, transcriptomic, and functional profiles, potentially driving tumor progression and therapy resistance. This study leverages integrated multi-omics and functional drug testing to systematically decipher the inter-nodular heterogeneity and evolutionary relationships within RCC.
Primary Objectives:
To delineate the cellular and genomic landscape of different intratumoral nodules in RCC using single-cell RNA sequencing (scRNA-seq), whole-exome sequencing (WES), and spatial transcriptomics.
To infer the potential clonal evolutionary relationships and driver-subordinate dynamics between coexisting nodules.
To characterize the differential drug sensitivity profiles of patient-derived microtumor (PTC) models established from distinct nodules.
To integrate multi-omics data with drug response data to explore underlying mechanisms of drug resistance.
Study Design and Methods: This is a single-center, prospective, basic science study. We will enroll 10 treatment-naïve patients with locally advanced RCC (tumor diameter ≥7 cm, with regional lymph node metastasis but no distant metastasis) scheduled for radical nephrectomy. Intraoperatively or immediately post-resection, each grossly multinodular tumor will be sectioned. Three dominant nodules (labeled T1, T2, T3 by size) will be identified from each specimen. From each nodule, four matched samples will be collected for: 1) scRNA-seq, 2) WES, 3) spatial transcriptomics, and 4) generation of 3D patient-derived tumor cell (PTC) microtumor models.
Analyses: Bioinformatic integration of scRNA-seq, WES, and spatial data will be performed to construct maps of cellular composition, genetic alterations, and their spatial distribution across nodules. Pseudotime trajectory analysis will be applied to infer potential evolutionary sequences. PTC models will undergo ex vivo drug sensitivity testing (e.g., against axitinib, pembrolizumab, and their combination). Differential response data will be correlated with omics-derived features (e.g., specific mutant alleles, cell subtype abundances, pathway activities) to identify candidate resistance mechanisms.
Significance: This is the first study to systematically investigate intratumoral nodular heterogeneity in RCC at a multi-omics level coupled with functional validation. Findings are expected to provide novel insights into RCC tumorigenesis and progression, potentially revealing new biomarkers for prognosis and therapeutic targets to overcome resistance.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study Cohort | – | Diagnostic Test: Multi-region Tumor Sampling and Integrated Multi-omics Analysis and Microtumor PTC Drug Sensitivity AssayAll 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Multi-region Tumor Sampling and Integrated Multi-omics Analysis and Microtumor PTC Drug Sensitivity AssayThis 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. | Diagnostic test | Study Cohort |
Primary outcome
Identification of Intra-tumoral Nodule Driving Relationships
Time frame: Through study completion, an average of 16 months
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.
2 secondary outcomes
Correlation between Ex Vivo Drug Sensitivity and Multi-omics Features
Time frame: Through study completion, an average of 24 months
Characterization of Inter-nodular Heterogeneity at Single-Cell Resolution
Time frame: Through study completion, an average of 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Renal Cell Carcinoma (Kidney Cancer)
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
RecruitingPhase 2/3
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma
Not yet recruitingPhase 2
Toripalimab and Lenvatinib With or Without SBRT Before Surgery for Non-Clear Cell Kidney Cancer
Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell Carcinoma
Not yet recruitingPhase 2
Pucotenlimab, Lenvatinib, and SBRT Before Surgery for Localized Clear Cell Renal Cell Carcinoma
Localized Clear Cell Renal Cell Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
An observational study of Renal Cell Carcinoma (Kidney Cancer), run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 20 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xiongjun Ye (8613910380916, yexiongjun@cicams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of Intra-tumoral Nodule Driving Relationships (time frame: Through study completion, an average of 16 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2026.