Heterogeneity of Treatment Effects of Adding Locoregional Therapies to Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma (ISMIO-026)
Heterogeneity of Treatment Effects of Adding Locoregional Therapies to Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma Based on Clinical and Multiregional, Multiphase Contrast-Enhanced CT/MRI Features (ISMIO-026)
uHCC imposes a substantial disease burden in China and the Asia-Pacific region. Atezo+Bev is an important first-line regimen for patients who have not received prior systemic therapy; however, not all patients achieve adequate and durable tumor control. In clinical practice, ablation, radiotherapy, or transarterial therapy is often added to Atezo+Bev to intensify intrahepatic disease control. The indications, timing, efficacy, and risk of liver-function impairment vary across LRTs. Most existing studies report average treatment effects and often use TACE as a fixed backbone, and therefore do not directly identify which patients receiving Atezo+Bev should receive early LRTs.
Using target trial emulation and HTE analysis, this study will integrate baseline clinical variables with pretreatment contrast-enhanced CT/MRI features to estimate the CATE of early LRT initiation and identify patients likely to achieve greater survival benefit.
調査の概要
状態
条件
研究の種類
入学 (推定)
連絡先と場所
研究連絡先
- 名前：Jian Lu
- 電話番号：13616106021
- メール：lujian43307131@126.com
研究場所
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Jiangsu
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Nanjing、Jiangsu、中国、213003
- Zhongda hospital
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コンタクト：
- Jun-Hao Mei
- 電話番号：15052007938
- メール：jh_mei240225@126.com
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
サンプリング方法
調査対象母集団
説明
Inclusion Criteria:
- Age ≥18 years on the index date.
- Receipt of at least one dose each of atezolizumab and bevacizumab as part of the same first-line combination regimen, with an interval of ≤28 days between the first administrations of the two drugs.
- At least one intrahepatic lesion amenable to a protocol-specified LRT on the index date, with no absolute contraindication to Atezo+Bev or to all feasible LRTs.
- A clinical, radiologic, or pathologic diagnosis of uHCC on or before the index date; baseline EHS is permitted.
- Survival status or the date last known alive after the index date can be ascertained.
- No systemic therapy for HCC before the regimen initiation date.
- No LRT within 60 days before the index date or between baseline imaging and the index date; earlier prior LRTs are permitted provided that an untreated, measurable intrahepatic lesion remains.
- A technically adequate baseline contrast-enhanced CT/MRI examination and at least one untreated intrahepatic lesion that can be delineated and evaluated.
- Baseline ECOG performance status of 0-2.
Exclusion Criteria:
- Another primary malignancy requiring active systemic treatment on the index date, except for a malignancy that has been cured and has a low risk of recurrence.
- Participation on the index date in an interventional study that could affect treatment allocation or outcome assessment.
- Suitability for immediate curative resection or liver transplantation following multidisciplinary assessment.
- An absolute contraindication to Atezo+Bev or to all feasible LRTs.
- Active autoimmune disease or immunodeficiency requiring systemic immunosuppression or constituting a contraindication to atezolizumab.
Inadequately controlled high-risk esophageal/gastric varices, recent variceal bleeding, an uncorrected bleeding tendency, or clinically significant coagulopathy.
- Inability to determine the index date, primary treatment strategy, OS outcome/censoring date, or absence of a technically adequate baseline contrast-enhanced CT/MRI examination.
研究計画
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 |
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トレーニングコホート
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Retrospective validation cohort
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Prospective validation cohort
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Biological validation cohort
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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 |
|---|---|---|
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Overall survival
時間枠：through study completion, an average of 1 year
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With OS as the primary outcome, to estimate the overall treatment effect and CATE of initiating LRTs within 60 days after Atezo+Bev initiation versus not initiating LRTs within 60 days; and to integrate baseline clinical variables with multiregional radiomic, dynamic/habitat, and deep representation features from pretreatment contrast-enhanced CT/MRI to develop and validate an HTE decision model.
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through study completion, an average of 1 year
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Model calibration
時間枠：through study completion, an average of 1 year
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through study completion, an average of 1 year
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Benefit ranking
時間枠：through study completion, an average of 1 year
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through study completion, an average of 1 year
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PFS/mPFS
時間枠：through study completion, an average of 1 year
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Defined as the time from index date to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1 or mRECIST.
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through study completion, an average of 1 year
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
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Adverse event
時間枠：through study completion, an average of 1 year
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To describe and compare the spectrum and severity of AEs between the two strategies and within their subgroups, with particular attention to hemorrhage, hypertension, hepatotoxicity, immune-related AEs, and complications associated with each type of LRT.
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through study completion, an average of 1 year
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協力者と研究者
スポンサー
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- ISMIO-026
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?
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
米国FDA規制機器製品の研究
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