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
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 67
- 主要终点
- Progression-Free Survival According to Baseline ctDNA Status
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 14 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Patient-Specific Tumor-Informed ctDNA Monitoring (Diagnostic Test)
结局指标
主要结局
Progression-Free Survival According to Baseline ctDNA Status
时间窗: 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.
Objective Response Rate According to Baseline ctDNA Status
时间窗: 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.
次要结局
- 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)