Personalized ctDNA Monitoring for Predicting Immunotherapy Outcomes in Advanced Non-Clear Cell Renal Cell Carcinoma
2026年8月17日 更新者：Hao Zeng、West China Hospital
Patient-Specific Circulating Tumor DNA Monitoring for Prediction of Immunotherapy Response and Prognostic Stratification in Advanced Non-Clear Cell Renal Cell Carcinoma: A Prospective Observational Cohort Study
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.
研究概览
详细说明
Patients with unresectable or metastatic non-clear cell renal cell carcinoma who are scheduled to receive immune checkpoint inhibitor-based systemic therapy according to routine clinical practice will be prospectively enrolled. Treatment regimens may include immune checkpoint inhibitor plus targeted therapy, dual immune checkpoint blockade, or immune checkpoint inhibitor monotherapy. Treatment selection will not be determined by this study.
For each participant, tumor tissue and matched normal peripheral blood will be analyzed to identify patient-specific somatic variants and establish a personalized tumor-informed ctDNA assay. Peripheral blood for longitudinal ctDNA monitoring will be collected before treatment, during early treatment, at the first radiographic assessment, during subsequent radiographic evaluations when feasible, and at disease progression or treatment discontinuation.
The primary analyses will compare progression-free survival and objective response rate between patients with detectable and undetectable baseline ctDNA. Secondary analyses will evaluate overall survival, disease control rate, and duration of response. Exploratory analyses will characterize longitudinal ctDNA patterns, including persistently negative, positive-to-negative, persistently positive, and negative-to-positive patterns, and investigate their associations with clinical outcomes, radiographic tumor burden, and the timing of disease progression.
Research ctDNA results will be used for scientific analysis and supportive clinical assessment and will not serve as the primary basis for treatment decisions.
研究类型
观察性的
注册 (估计的)
67
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习联系方式
- 姓名：Hao Zeng, MD, PhD
- 电话号码：+86-18980602129
- 邮箱：kucaizeng@163.com
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
- 孩子
- 成人
- 年长者
接受健康志愿者
不
取样方法
非概率样本
研究人群
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.
描述
Inclusion Criteria:
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.
Exclusion Criteria:
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.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
队列和干预
团体/队列 |
干预/治疗 |
|---|---|
|
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.
|
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.
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Progression-Free Survival According to Baseline ctDNA Status
大体时间：From treatment initiation until disease progression or death, assessed through December 2028
|
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
大体时间：From treatment initiation through disease progression, assessed approximately every 8-12 weeks through December 2028
|
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
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Overall Survival According to Baseline ctDNA Status
大体时间：From treatment initiation until death from any cause, assessed through December 2028
|
Overall survival will be defined as the time from initiation of immune checkpoint inhibitor-based systemic therapy to death from any cause and will be compared 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
大体时间：From treatment initiation through disease progression, assessed through December 2028
|
Disease control rate will be defined as the proportion of participants achieving complete response, partial response, or stable disease as the best overall response according to RECIST version 1.1 and will be compared according to baseline ctDNA status.
|
From treatment initiation through disease progression, assessed through December 2028
|
|
Duration of Response According to Baseline ctDNA Status
大体时间：From first documented response until disease progression or death, assessed through December 2028
|
Among participants achieving complete or partial response, duration of response will be defined as the time from the first documented objective response until radiographic disease progression or death from any cause, whichever occurs first.
|
From first documented response until disease progression or death, assessed through December 2028
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Hao Zeng, Doctor、West China Hospital
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (估计的)
2026年9月1日
初级完成 (估计的)
2028年12月30日
研究完成 (估计的)
2028年12月30日
研究注册日期
首次提交
2026年8月17日
首先提交符合 QC 标准的
2026年8月17日
首次发布 (实际的)
2026年8月20日
研究记录更新
最后更新发布 (实际的)
2026年8月20日
上次提交的符合 QC 标准的更新
2026年8月17日
最后验证
2026年8月1日
更多信息
与本研究相关的术语
其他研究编号
- WCH-nccRCC-ctDNA
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
是的
IPD 计划说明
There is a plan to make IPD and related data dictionaries available.
IPD 共享时间框架
Data would be available starting from the time when summary data are published orotherwise made available, for 3 years.
IPD 共享访问标准
Other researchers access the data by sending an email to our PI.
IPD 共享支持信息类型
- 研究方案
- 国际碳纤维联合会
- 企业社会责任
药物和器械信息、研究文件
研究美国 FDA 监管的药品
不
研究美国 FDA 监管的设备产品
不
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.