Personalized ctDNA Monitoring for Predicting Immunotherapy Outcomes in Advanced Non-Clear Cell Renal Cell Carcinoma

NCT07776483 | Not Yet Recruiting

• 1 other identifier: WCH-nccRCC-ctDNA
• Study Type: observational
• Target: 67
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, non-interventional observational cohort study evaluating the clinical utility of patient-specific circulating tumor DNA (ctDNA) monitoring in patients with advanced non-clear cell renal cell carcinoma (nccRCC) receiving immune checkpoint inhibitor-based systemic therapy. Tumor-informed personalized ctDNA assays will be developed based on tumor tissue and matched normal blood samples, and ctDNA will be longitudinally assessed at predefined time points during treatment. The primary objectives are to evaluate the associations of baseline ctDNA status with progression-free survival and objective response rate. Secondary and exploratory analyses will assess overall survival, disease control, duration of response, longitudinal ctDNA dynamics, radiographic tumor burden, and molecular progression.

Conditions

Non-Clear Cell Renal Cell Carcinoma

Keywords

Circulating Tumor DNA; Non-Clear Cell Renal Cell Carcinoma; Immune Checkpoint Inhibitor; Personalized ctDNA Monitoring; Liquid Biopsy

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival According to Baseline ctDNA Status

  Progression-free survival (PFS) will be defined as the time from initiation of immune checkpoint inhibitor-based systemic therapy to radiographic disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first. PFS will be compared between participants with detectable and undetectable baseline ctDNA. The primary effect estimate will be the hazard ratio with its 95% confidence interval.

  From treatment initiation until disease progression or death, assessed through December 2028

• Objective Response Rate According to Baseline ctDNA Status

  Objective response rate (ORR) will be defined as the proportion of participants achieving a best overall response of complete response or partial response according to RECIST version 1.1. ORR will be compared between participants with detectable and undetectable baseline ctDNA.

  From treatment initiation through disease progression, assessed approximately every 8-12 weeks through December 2028

Secondary Outcomes (3)

• Overall Survival According to Baseline ctDNA Status

  From treatment initiation until death from any cause, assessed through December 2028

• Disease Control Rate According to Baseline ctDNA Status

  From treatment initiation through disease progression, assessed through December 2028

• Duration of Response According to Baseline ctDNA Status

  From first documented response until disease progression or death, assessed through December 2028

Study Arms (1)

Advanced nccRCC Cohort

Patients with unresectable or metastatic non-clear cell renal cell carcinoma who are initiating immune checkpoint inhibitor-based systemic therapy according to routine clinical practice. Participants will undergo longitudinal patient-specific tumor-informed ctDNA monitoring and will subsequently be classified according to baseline ctDNA status and longitudinal ctDNA dynamics for outcome analyses.

Diagnostic Test: Patient-Specific Tumor-Informed ctDNA Monitoring

Interventions

Patient-Specific Tumor-Informed ctDNA Monitoring DIAGNOSTIC_TEST

Tumor tissue and matched normal blood will undergo genomic analysis to identify patient-specific somatic variants for development of a personalized tumor-informed ctDNA assay. Longitudinal plasma samples will subsequently be analyzed for ctDNA during systemic therapy. The assay is used for research monitoring and does not determine treatment selection.

Advanced nccRCC Cohort

Eligibility Criteria

• Age: 14 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with histologically confirmed advanced non-clear cell renal cell carcinoma treated at West China Hospital, Sichuan University, who are scheduled to initiate immune checkpoint inhibitor-based systemic therapy according to routine clinical practice. Eligible histological subtypes include papillary renal cell carcinoma, chromophobe renal cell carcinoma, TFE3-rearranged renal cell carcinoma, FH-deficient renal cell carcinoma, collecting duct carcinoma, renal medullary carcinoma, and other rare non-clear cell renal cell carcinoma subtypes.

You may qualify if:

• Participants must meet all of the following criteria:
• Age 14 years or older, with no restriction based on sex.
• Histologically confirmed renal cell carcinoma classified as non-clear cell renal cell carcinoma. Immunohistochemical or molecular testing may be used when necessary to establish the histological subtype. Eligible subtypes include papillary renal cell carcinoma, chromophobe renal cell carcinoma, TFE3-rearranged renal cell carcinoma, FH-deficient renal cell carcinoma, collecting duct carcinoma, renal medullary carcinoma, and other rare non-clear cell renal cell carcinoma subtypes.
• Unresectable or metastatic renal cell carcinoma with at least one measurable lesion according to RECIST version 1.1.
• Scheduled, according to routine clinical care, to initiate immune checkpoint inhibitor-based systemic therapy, including an immune checkpoint inhibitor combined with targeted therapy, dual immune checkpoint blockade, or immune checkpoint inhibitor monotherapy. The number of previous lines of systemic therapy is not restricted, provided that prior treatment history, specific regimens, and best responses can be adequately documented.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and an estimated life expectancy greater than 3 months.
• Ability and willingness to provide written informed consent and comply with protocol-specified sample collection, examinations, and follow-up.

You may not qualify if:

• Participants meeting any of the following criteria will be excluded:
• The planned systemic treatment does not contain an immune checkpoint inhibitor and consists only of chemotherapy, targeted therapy, or another non-immunotherapy systemic treatment.
• Untreated, symptomatic, or clinically unstable central nervous system metastases or leptomeningeal metastases.
• Another active malignancy of a different primary site or histological type within the previous 3 years, except adequately controlled malignancies such as papillary thyroid carcinoma, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cervical carcinoma in situ.
• Major surgery or severe trauma within 4 weeks before enrollment without adequate recovery.
• Uncontrolled severe infection or another serious comorbidity, including active tuberculosis, active hepatitis B or C, severe cardiac insufficiency, persistent symptomatic arrhythmia, uncontrolled hypertension, or serious cardiovascular or cerebrovascular events such as myocardial infarction, unstable angina, or cerebrovascular accident within 6 months before enrollment.
• Pregnancy or breastfeeding.
• Severe psychiatric, cognitive, or behavioral impairment that prevents understanding of the study, provision of required samples, or completion of protocol-specified examinations and follow-up.
• Failure to establish a patient-specific ctDNA monitoring panel because of inadequate tumor tissue quantity or quality, inability to identify suitable patient-specific somatic variants, or other technical reasons.
• Any other condition that, in the investigator's judgment, may increase the risks associated with study participation, interfere with interpretation of the study results, or compromise protocol compliance.

Sponsors & Collaborators

• West China Hospital: lead

Biospecimen

Retention: SAMPLES WITH DNA

Archived or newly obtained tumor tissue, matched normal peripheral blood, and longitudinal peripheral blood plasma samples will be collected. Tumor tissue and matched normal blood will be used for whole-exome sequencing and development of a patient-specific tumor-informed ctDNA assay. Plasma samples will be collected for longitudinal ctDNA analysis at baseline, 4-8 weeks after treatment initiation, at the first radiographic assessment at approximately 8-12 weeks, during subsequent radiographic assessments when feasible, and at disease progression or treatment discontinuation.

Study Officials

• Hao Zeng, Doctor

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hao Zeng, MD, PhD

CONTACT

+86-18980602129; kucaizeng@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 17, 2026
• First Posted: August 20, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: August 20, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Data would be available starting from the time when summary data are published orotherwise made available, for 3 years.
• Access Criteria: Other researchers access the data by sending an email to our PI.