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

Fudan University

Status: Not yet enrolling

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

Treatments: Procedure: Surgery; Diagnostic Test: TDTP-RECIST; Drug: GOLP regimen

Study type: Interventional

Funder types: Other

Identifiers

NCT07208526

ZSAB-TDTP-transGOLP

Details and patient eligibility

About

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).

Full 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.

Enrollment: 270 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

-

Subjects who meet any of the following exclusion criteria are not permitted to enroll in this study:

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

270 participants in 3 patient groups, including a placebo group

Medication Group

Placebo Comparator group

Description:

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.

Treatment:

Drug: GOLP regimen

Surgery Group

Experimental group

Description:

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).

Treatment:

Procedure: Surgery

TDTP Group

Experimental group

Description:

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.

Treatment:

Diagnostic Test: TDTP-RECIST