Personalized ctDNA Monitoring for Predicting Immunotherapy Outcomes in Advanced Non-Clear Cell Renal Cell Carcinoma
17 августа 2026 г. обновлено: 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.
Обзор исследования
Статус
Еще не набирают
Вмешательство/лечение
Подробное описание
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.
Тип исследования
Наблюдательный
Регистрация (Оцененный)
67
Контакты и местонахождение
В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.
Контакты исследования
- Имя: Hao Zeng, MD, PhD
- Номер телефона: +86-18980602129
- Электронная почта: kucaizeng@163.com
Критерии участия
Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.
Критерии приемлемости
Возраст, подходящий для обучения
- Ребенок
- Взрослый
- Пожилой взрослый
Принимает здоровых добровольцев
Нет
Метод выборки
Невероятностная выборка
Исследуемая популяция
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.
Описание
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.
Учебный план
В этом разделе представлена подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.
Как устроено исследование?
Детали дизайна
Когорты и вмешательства
Группа / когорта |
Вмешательство/лечение |
|---|---|
|
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.
|
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Progression-Free Survival According to Baseline ctDNA Status
Временное ограничение: 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
Временное ограничение: 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
|
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Overall Survival According to Baseline ctDNA Status
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
|
Соавторы и исследователи
Здесь вы найдете людей и организации, участвующие в этом исследовании.
Спонсор
Следователи
- Главный следователь: Hao Zeng, Doctor, West China Hospital
Даты записи исследования
Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.
Изучение основных дат
Начало исследования (Оцененный)
1 сентября 2026 г.
Первичное завершение (Оцененный)
30 декабря 2028 г.
Завершение исследования (Оцененный)
30 декабря 2028 г.
Даты регистрации исследования
Первый отправленный
17 августа 2026 г.
Впервые представлено, что соответствует критериям контроля качества
17 августа 2026 г.
Первый опубликованный (Действительный)
20 августа 2026 г.
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
20 августа 2026 г.
Последнее отправленное обновление, отвечающее критериям контроля качества
17 августа 2026 г.
Последняя проверка
1 августа 2026 г.
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Другие идентификационные номера исследования
- WCH-nccRCC-ctDNA
Планирование данных отдельных участников (IPD)
Планируете делиться данными об отдельных участниках (IPD)?
ДА
Описание плана IPD
There is a plan to make IPD and related data dictionaries available.
Сроки обмена IPD
Data would be available starting from the time when summary data are published orotherwise made available, for 3 years.
Критерии совместного доступа к IPD
Other researchers access the data by sending an email to our PI.
Совместное использование IPD Поддерживающий тип информации
- STUDY_PROTOCOL
- МКФ
- КСО
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Нет
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
Нет
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .