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

NCT ID: NCT07208526

Last Updated: 2025-10-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 270 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-01
• Study Completion Date: 2028-12-31

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).

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.

Conditions

Intrahepatic Cholangiocarcinoma (Icc); Conversion Therapy; TDTP-RECIST; GOLP Regimen

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

GOLP regimen

Intervention Type: DRUG

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

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).

Group Type: EXPERIMENTAL

Surgery

Intervention Type: PROCEDURE

R0 resection

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.

Group Type: EXPERIMENTAL

TDTP-RECIST

Intervention Type: DIAGNOSTIC_TEST

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

Interventions

GOLP regimen

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

Intervention Type: DRUG

Surgery

R0 resection

Intervention Type: PROCEDURE

TDTP-RECIST

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

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

-

Subjects eligible to participate in this study must meet all of the following criteria:

1. Male or female aged 18-75 years;

2. Patients must provide signed informed consent prior to enrollment, demonstrating the ability to understand and willingness to sign the written informed consent form;

3. Pathologically confirmed diagnosis of intrahepatic cholangiocarcinoma;

4. Locally advanced disease, failure to achieve R0 resection, and absence of distant metastasis;

5. At least one measurable lesion;

6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0;

7. Child-Pugh class A liver function;

Exclusion Criteria

-

1. Pathologically diagnosed hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, or other non-cholangiocarcinoma malignant components;

2. Patients with postoperative recurrence, or those who have previously received PD-1/PD-L1 antibodies, CTLA-4 antibodies, lenvatinib, or chemotherapy;

3. History or current diagnosis of other malignancies;

4. Active tuberculosis infection;

5. Active, known, or suspected autoimmune disease;

6. History of interstitial lung disease, or non-infectious pneumonitis requiring steroid treatment;

7. Significant clinically significant bleeding symptoms within 3 months prior to enrollment, or clear bleeding tendency;

8. Suspected allergy to the investigational drug(s).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Geriatric Medical Center

OTHER

Sponsor Role: collaborator

Shanghai Jiao Tong University Affiliated Sixth People's Hospital

OTHER

Sponsor Role: collaborator

Shanghai 10th People's Hospital

OTHER

Sponsor Role: collaborator

Oriental Hepatobiliary Surgery Hospital Affiliated to Naval Military Medical University

UNKNOWN

Sponsor Role: collaborator

Shanghai Zhongshan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jia Fan

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jia Fan, MD&PhD

Role: STUDY_CHAIR

Shanghai Zhongshan Hospital

Locations

Zhongshan hospital, Shanghai

Shanghai, , China

Countries

China

Central Contacts

Xiao-Yong Huang, MD

Role: CONTACT

huang.xiaoyong@zs-hospital.sh.cn

+8615021519215

Guo-Ming Shi, MD

Role: CONTACT

shi.guoming@zs-hospital.sh.cn

+8613916969578

Facility Contacts

Xiao-yong Huang, MD

Role: primary

huang.xiaoyong@zs-hospital.sh.cn

+8615021519215

Guo-Ming Shi, MD

Role: backup

shi.guoming@zs-hospital.sh.cn

+8613916969578

References

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.

Reference Type: BACKGROUND

PMID: 40889502 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 36928584 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 38823398 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 37075781 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 39867595 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 36260350 (View on PubMed)

Other Identifiers

ZSAB-TDTP-transGOLP

Identifier Type: -

Identifier Source: org_study_id