NCT07208526

Brief Summary

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).

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
270

participants targeted

Target at P75+ for not_applicable

Timeline
33mo left

Started Dec 2025

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress14%
Dec 2025Dec 2028

First Submitted

Initial submission to the registry

September 28, 2025

Completed
8 days until next milestone

First Posted

Study publicly available on registry

October 6, 2025

Completed
2 months until next milestone

Study Start

First participant enrolled

December 1, 2025

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2028

Expected
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2028

Last Updated

October 6, 2025

Status Verified

September 1, 2025

Enrollment Period

2.6 years

First QC Date

September 28, 2025

Last Update Submit

September 28, 2025

Conditions

Intrahepatic Cholangiocarcinoma (Icc)Conversion TherapyTDTP-RECISTGOLP Regimen

Outcome Measures

Primary Outcomes (1)

  • Overall survival

    the time period from the randomization of the patient to the death event due to any reason

    24 months

Secondary Outcomes (6)

  • 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

  • +1 more secondary outcomes

Other Outcomes (1)

  • Exploratory markers

    24 months

Study Arms (3)

Medication Group

PLACEBO COMPARATOR

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.

Drug: GOLP regimen

Surgery Group

EXPERIMENTAL

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).

Procedure: Surgery

TDTP Group

EXPERIMENTAL

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.

Diagnostic Test: TDTP-RECIST

Interventions

GOLP regimenDRUG

PD1 antibody (Toripalimab) combined with GEMOX chemotherapy and Lenvatinib neoadjuvant treatment

Medication Group
SurgeryPROCEDURE

R0 resection

Surgery Group
TDTP-RECISTDIAGNOSTIC_TEST

Treatment selection between continued GOLP therapy and surgical R0 resection based on TDTP-RECIST criteria.

TDTP Group

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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;

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Zhongshan hospital, Shanghai

Shanghai, 200032, China

Location

Related Publications (6)

  • 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):1334-1345. doi: 10.1016/S1470-2045(25)00376-6. Epub 2025 Aug 29.

    PMID: 40889502BACKGROUND

  • 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 Mar 17;8(1):106. doi: 10.1038/s41392-023-01317-7.

    PMID: 36928584BACKGROUND

  • 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 J, Morgan C, Rokutanda N, Zotkiewicz M, Vogel A, Valle JW. Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 study. Lancet Gastroenterol Hepatol. 2024 Aug;9(8):694-704. doi: 10.1016/S2468-1253(24)00095-5. Epub 2024 May 29.

    PMID: 38823398BACKGROUND

  • 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 randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Jun 3;401(10391):1853-1865. doi: 10.1016/S0140-6736(23)00727-4. Epub 2023 Apr 16.

    PMID: 37075781BACKGROUND

  • 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: 39867595BACKGROUND

  • 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: 36260350BACKGROUND

MeSH Terms

Conditions

CholangiocarcinomaCirrhosis, Familial, with Pulmonary Hypertension

Interventions

Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasms

Study Officials

  • Jia Fan, MD&PhD

    Shanghai Zhongshan Hospital

    STUDY CHAIR

Central Study Contacts

Xiao-Yong Huang, MD

CONTACT

+8615021519215huang.xiaoyong@zs-hospital.sh.cn

Guo-Ming Shi, MD

CONTACT

+8613916969578shi.guoming@zs-hospital.sh.cn

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

September 28, 2025

First Posted

October 6, 2025

Study Start

December 1, 2025

Primary Completion (Estimated)

June 30, 2028

Study Completion (Estimated)

December 31, 2028

Last Updated

October 6, 2025

Record last verified: 2025-09

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)