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.
調査の概要
詳細な説明
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.
研究の種類
観察的
入学 (推定)
67
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Hao Zeng, MD, PhD
- 電話番号：+86-18980602129
- メール：kucaizeng@163.com
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 子
- 大人
- 高齢者
健康ボランティアの受け入れ
いいえ
サンプリング方法
非確率サンプル
調査対象母集団
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.
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
|
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.
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Progression-Free Survival According to Baseline ctDNA Status
時間枠：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
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Overall Survival According to Baseline ctDNA Status
時間枠：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
時間枠：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
時間枠：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
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- 主任研究者：Hao Zeng, Doctor、West China Hospital
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (推定)
2026年9月1日
一次修了 (推定)
2028年12月30日
研究の完了 (推定)
2028年12月30日
試験登録日
最初に提出
2026年8月17日
QC基準を満たした最初の提出物
2026年8月17日
最初の投稿 (実際)
2026年8月20日
学習記録の更新
投稿された最後の更新 (実際)
2026年8月20日
QC基準を満たした最後の更新が送信されました
2026年8月17日
最終確認日
2026年8月1日
詳しくは
本研究に関する用語
キーワード
その他の研究ID番号
- WCH-nccRCC-ctDNA
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
はい
IPD プランの説明
There is a plan to make IPD and related data dictionaries available.
IPD 共有時間枠
Data would be available starting from the time when summary data are published orotherwise made available, for 3 years.
IPD 共有アクセス基準
Other researchers access the data by sending an email to our PI.
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- ICF
- CSR
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
いいえ
米国FDA規制機器製品の研究
いいえ
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。