A Multicenter Randomized Controlled Study on Surgical Decision-Making Guided by the TDTP-RECIST Evaluation System for Locally Advanced Intrahepatic Cholangiocarcinoma Following GOLP Conversion Therapy
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 270
- 试验地点
- 1
- 主要终点
- Overall survival
研究概览
简要总结
This project aims to conduct a prospective, multicenter, randomized controlled clinical trial. The study plans to enroll 270 patients with locally advanced iCCA who have successfully undergone GOLP conversion therapy. Participants will be randomized at a 1:2:2 ratio into three arms: Control Arm (continued medication), Direct Surgery Arm, and TDTP-RECIST Assessment Arm. The primary endpoint is Overall Survival (OS).
详细描述
Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive malignancy with a poor prognosis, and a majority of patients are ineligible for curative surgery upon initial diagnosis. Although the GOLP conversion therapy regimen, pioneered by our research team, has demonstrated promising results in preliminary studies-achieving an 80% objective response rate and a 63% R0 resection rate-its clinical value requires validation through high-level evidence-based medicine. Concurrently, the conventional RECIST 1.1 criteria are inadequate for accurately assessing treatment response in iCCA, leading to challenges in surgical decision-making. To address this, we have developed the innovative TDTP-RECIST evaluation system, which preliminary data suggest can more precisely predict surgical opportunities and survival benefits.
This multicenter randomized controlled trial aims to primarily validate the clinical value of the GOLP regimen as conversion therapy for locally advanced intrahepatic cholangiocarcinoma (iCCA), thereby providing high-level evidence-based medical support for its establishment as a standard treatment protocol. Furthermore, the study seeks to verify the efficacy and superiority of the TDTP-RECIST evaluation system in guiding surgical decision-making following conversion therapy for iCCA. The ultimate goals are to establish an individualized treatment pathway based on TDTP-RECIST assessments, optimize the timing of surgery, reduce unnecessary surgical interventions and healthcare resource waste, and consequently offer a reliable decision-making framework for the conversion therapy of locally advanced iCCA. This will provide a precise and powerful tool to facilitate the transition from "unresectable" to "curable" disease.
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
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects eligible to participate in this study must meet all of the following criteria:
- •Male or female aged 18-75 years;
- •Patients must provide signed informed consent prior to enrollment, demonstrating the ability to understand and willingness to sign the written informed consent form;
- •Pathologically confirmed diagnosis of intrahepatic cholangiocarcinoma;
- •Locally advanced disease, failure to achieve R0 resection, and absence of distant metastasis;
- •At least one measurable lesion;
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0;
- •Child-Pugh class A liver function;
排除标准
- •Subjects who meet any of the following exclusion criteria are not permitted to enroll in this study:
- •Pathologically diagnosed hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, or other non-cholangiocarcinoma malignant components;
- •Patients with postoperative recurrence, or those who have previously received PD-1/PD-L1 antibodies, CTLA-4 antibodies, lenvatinib, or chemotherapy;
- •History or current diagnosis of other malignancies;
- •Active tuberculosis infection;
- •Active, known, or suspected autoimmune disease;
- •History of interstitial lung disease, or non-infectious pneumonitis requiring steroid treatment;
- •Significant clinically significant bleeding symptoms within 3 months prior to enrollment, or clear bleeding tendency;
- •Suspected allergy to the investigational drug(s).
研究组 & 干预措施
Medication Group
Upon randomization, patients will continue to receive the GOLP regimen for up to 8 cycles, followed by maintenance therapy with lenvatinib plus toripalimab for one year, until disease progression, withdrawal from the study, or the occurrence of intolerable toxicity.
干预措施: GOLP regimen (Drug)
Surgery Group
Surgical resection is to be performed within 2-4 weeks after randomization, followed by adjuvant therapy with capecitabine at a dose of 1250 mg/m² twice daily, administered orally for eight cycles (each cycle consists of 14 days of medication followed by a 7-day rest period, constituting a 3-week treatment cycle).
干预措施: Surgery (Procedure)
TDTP Group
Following randomization, patients will be evaluated using the TDTP-RECIST system. Those who meet the predetermined cutoff value (63%) will proceed to surgical resection. Patients not meeting the cutoff value will continue the GOLP regimen for up to 8 cycles, during which those who subsequently meet the cutoff value will undergo surgery. Postoperative adjuvant therapy will consist of capecitabine (1250 mg/m², BID, orally) for eight cycles (each cycle: 14 days on, 7 days off, constituting a 3-week cycle). Patients who do not meet the cutoff value after 8 cycles of GOLP therapy will receive maintenance therapy with lenvatinib plus toripalimab for up to one year or until intolerable toxicity occurs.
干预措施: TDTP-RECIST (Diagnostic Test)
结局指标
主要结局
Overall survival
时间窗: 24 months
the time period from the randomization of the patient to the death event due to any reason
次要结局
- Event-free survival(24 months)
- Objective response rate(6 months)
- Pathological remission rate(6 months)
- Recurrence-free survival(24 months)
- R0 Resection Rate(12 months)
- Adverse events(12 months)
研究者
Jia Fan
Professor
Shanghai Zhongshan Hospital