A Randomized Trial of Surgical Decision-Making Guided by TDTP-RECIST

Official title

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

Overview

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).

Detailed description

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.

Interventions

• Drug GOLP regimen
  PD1 antibody (Toripalimab) combined with GEMOX chemotherapy and Lenvatinib neoadjuvant treatment
• Procedure Surgery
  R0 resection
• Diagnostic test TDTP-RECIST
  Treatment selection between continued GOLP therapy and surgical R0 resection based on TDTP-RECIST criteria.

Primary outcome measures

• Overall survival [Time frame: 24 months]

Secondary outcome measures (6)

• Event-free survival [Time frame: 24 months]
• Objective response rate [Time frame: 6 months]
• Pathological remission rate [Time frame: 6 months]
• Recurrence-free survival [Time frame: 24 months]
• R0 Resection Rate [Time frame: 12 months]
• Adverse events [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

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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;

Exclusion criteria

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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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Zhongshan hospital, Shanghai — Shanghai

Publications

• Shi G, Huang X, Li X, Liang F, Gao Q, Zhang D, Lu J, Ji Y, Hu Z, Chen Y, Qiu S, Yi Y, Zhu X, Sun H, Shi Y, Peng M, Wang X, Huang C, Ding Z, He Y, Shen Y, Xu Y, Xiao Y, Hu J, Zhou J, Fan J. Conversion therapy of tislelizumab plus lenvatinib and GEMOX in unresectable locally advanced biliary tract cancer (ZSAB-TransGOLP): a multicentre, prospective, phase 2 study. Lancet Oncol. 2025 Oct;26(10):1334- PMID 40889502
• Shi GM, Huang XY, Wu D, Sun HC, Liang F, Ji Y, Chen Y, Yang GH, Lu JC, Meng XL, Wang XY, Sun L, Ge NL, Huang XW, Qiu SJ, Yang XR, Gao Q, He YF, Xu Y, Sun J, Ren ZG, Fan J, Zhou J. Toripalimab combined with lenvatinib and GEMOX is a promising regimen as first-line treatment for advanced intrahepatic cholangiocarcinoma: a single-center, single-arm, phase 2 study. Signal Transduct Target Ther. 2023 M PMID 36928584
• Oh DY, He AR, Bouattour M, Okusaka T, Qin S, Chen LT, Kitano M, Lee CK, Kim JW, Chen MH, Suksombooncharoen T, Ikeda M, Lee MA, Chen JS, Potemski P, Burris HA 3rd, Ostwal V, Tanasanvimon S, Morizane C, Zaucha RE, McNamara MG, Avallone A, Cundom JE, Breder V, Tan B, Shimizu S, Tougeron D, Evesque L, Petrova M, Zhen DB, Gillmore R, Gupta VG, Dayyani F, Park JO, Buchschacher GL Jr, Rey F, Kim H, Wang PMID 38823398
• Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, Yau T, Klumpen HJ, Chan SL, Ozaka M, Verslype C, Bouattour M, Park JO, Barajas O, Pelzer U, Valle JW, Yu L, Malhotra U, Siegel AB, Edeline J, Vogel A; KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a PMID 37075781
• Colangelo M, Di Martino M, Polidoro MA, Forti L, Tober N, Gennari A, Pagano N, Donadon M. Management of intrahepatic cholangiocarcinoma: a review for clinicians. Gastroenterol Rep (Oxf). 2025 Jan 26;13:goaf005. doi: 10.1093/gastro/goaf005. eCollection 2025. PMID 39867595
• Moris D, Palta M, Kim C, Allen PJ, Morse MA, Lidsky ME. Advances in the treatment of intrahepatic cholangiocarcinoma: An overview of the current and future therapeutic landscape for clinicians. CA Cancer J Clin. 2023 Mar;73(2):198-222. doi: 10.3322/caac.21759. Epub 2022 Oct 19. PMID 36260350

Identifiers

NCT: NCT07208526 · ZSAB-TDTP-transGOLP

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗