A Multicenter, Parallel-Group, Cluster-Randomized Controlled Trial Evaluating an Artificial Intelligence Clinical Decision Support System for Selection of First-Line Immune Checkpoint Inhibitor-Based Therapy in Unresectable Hepatocellular Carcinoma
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 1,800
- 试验地点
- 1
- 主要终点
- Progression-Free Survival Assessed by Blinded Independent Central Review Using RECIST Version 1.1
研究概览
简要总结
This pragmatic, multicenter, cluster-randomized trial will evaluate whether a locked artificial intelligence (AI) clinical decision-support system can improve outcomes by helping multidisciplinary teams select first-line immune checkpoint inhibitor (ICI)-based systemic treatment for adults with unresectable hepatocellular carcinoma (HCC).
Twenty-six hospitals or independent HCC multidisciplinary teams will be randomly assigned in a 1:1 ratio to AI-assisted treatment selection or usual-care treatment selection. Approximately 1,800 participants will be enrolled. Eligible participants must already be considered suitable for first-line ICI-based systemic therapy; the study does not compare immunotherapy with no immunotherapy.
At AI-assisted sites, the system will use prespecified pretreatment information to estimate and compare expected outcomes across clinically appropriate, locally available, guideline-concordant ICI-based regimens. The AI output is advisory. Treating clinicians and patients retain responsibility for the final treatment decision, and reasons for not following an AI recommendation will be recorded. At usual-care sites, treatment will be selected through the standard multidisciplinary decision-making process without access to the AI output. Both groups will receive approved standard-of-care treatments.
The AI model, input definitions, preprocessing pipeline, decision rules, thresholds, and software version will be locked before enrollment of the first participant and will not be retrained or modified using trial outcome data. Both groups will use the same eligibility criteria, patient-registration time point, imaging schedule, follow-up schedule, and outcome definitions.
The primary outcome is progression-free survival assessed by blinded independent central imaging review. Overall survival is a key secondary outcome. Additional outcomes include tumor response, duration of response, safety, quality of life, treatment delivery, and implementation measures. This trial evaluates the clinical utility of a prespecified AI system rather than developing or optimizing another prediction model.
详细描述
Background and Rationale
Several first-line immune checkpoint inhibitor (ICI)-based systemic treatment options are available for patients with unresectable hepatocellular carcinoma (HCC), but their relative benefits and toxicity profiles vary between patients. The artificial intelligence (AI) clinical decision-support system evaluated in this trial was developed and externally validated in separate, completed retrospective multicenter studies before initiation of the registered trial. However, predictive performance in retrospective data alone cannot establish whether using the system improves treatment selection or patient outcomes. This prospective trial is therefore designed to evaluate the clinical utility of a prespecified and locked AI system when integrated into routine multidisciplinary care.
This ClinicalTrials.gov record pertains exclusively to the prospective cluster-randomized evaluation. The preceding retrospective model-development and external-validation studies are outside the scope of this registry record and are not included in the registered enrollment, study dates, treatment groups, or outcomes.
Study Design
This is a prospective, multicenter, pragmatic, open-label, two-arm, parallel-group, superiority, cluster-randomized controlled trial with blinded independent central review of the primary imaging endpoint.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
The trial is open-label at the participant, care-provider, and site-investigator levels because the use of AI-assisted decision support cannot be concealed. However, de-identified imaging studies for the primary progression-free survival endpoint will be assessed by an independent central review committee blinded to cluster assignment, AI recommendations, treatment-selection rationale, and treating hospital and, where feasible, the treatment regimen received.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or older.
- •Hepatocellular carcinoma confirmed by histology or cytology, or diagnosed using accepted noninvasive radiologic criteria.
- •Unresectable hepatocellular carcinoma for which first-line systemic therapy is indicated, including Barcelona Clinic Liver Cancer stage B disease that is unsuitable for or no longer benefiting from locoregional therapy, or stage C disease.
- •No prior systemic anticancer therapy for unresectable hepatocellular carcinoma.
- •Child-Pugh class A liver function.
- •Eastern Cooperative Oncology Group performance status of 0 or
- •Eligible and intended to receive at least one protocol-specified, guideline-concordant immune checkpoint inhibitor-based first-line regimen, as determined by the treating clinician before exposure to the study AI recommendation.
- •Eligibility confirmed and prospective participant registration completed before the final first-line treatment regimen is selected.
- •Baseline contrast-enhanced computed tomography or magnetic resonance imaging suitable for assessment according to Response Evaluation Criteria in Solid Tumors version 1.1 is available before initiation of first-line systemic therapy.
- •Required pretreatment clinical data are available within the protocol-specified assessment windows.
- •Able to provide written informed consent.
排除标准
- •Known combined hepatocellular-cholangiocarcinoma or another primary liver malignancy other than hepatocellular carcinoma.
- •A contraindication or clinical condition that makes all protocol-specified immune checkpoint inhibitor-based first-line regimens inappropriate according to applicable prescribing information and routine clinical practice.
- •Initiation of systemic therapy or completion of the final first-line regimen decision before prospective participant registration.
- •Exposure of the treating clinical team to the participant-specific AI recommendation before confirmation of eligibility and registration.
- •Concurrent anticancer treatment for another malignancy that would materially interfere with treatment selection or study outcome assessment.
- •Planned participation in another interventional study that dictates first-line systemic treatment or would interfere with study outcome assessment.
- •Inability to undergo protocol-required tumor imaging or follow-up assessments.
结局指标
主要结局
Progression-Free Survival Assessed by Blinded Independent Central Review Using RECIST Version 1.1
时间窗: From participant registration until radiographic disease progression or death from any cause, whichever occurs first, assessed up to 27 months
Progression-free survival is defined as the time from prospective participant registration to the first radiographically documented disease progression according to RECIST version 1.1, as determined by blinded independent central review, or death from any cause, whichever occurs first. Participants without either event will be censored at the date of their last adequate radiographic tumor assessment. Imaging assessments will follow the same prespecified schedule in both study groups.
次要结局
- Overall Survival(From participant registration until death from any cause, assessed up to 44 months)
- Objective Response Rate Assessed by Blinded Independent Central Review Using RECIST Version 1.1(From participant registration through the last tumor assessment before disease progression or initiation of new anticancer therapy, assessed up to 27 months)
- Duration of Response(From the first documented response that is subsequently confirmed until radiographic disease progression or death from any cause, assessed up to 27 months)
- Disease Control Rate(From participant registration through the last tumor assessment before disease progression or initiation of new anticancer therapy, assessed up to 27 months)
- Time to Treatment Failure(From participant registration until failure of the initial first-line treatment strategy or death from any cause, assessed up to 27 months)
- Percentage of Participants With Grade 3 or Higher Treatment-Emergent Adverse Events(From the first dose of first-line systemic therapy through 90 days after the last dose, assessed up to 44 months)
- Change From Baseline in Patient-Reported Global Health Status and Quality of Life at 6 Months(Baseline and 6 months after participant registration)