Conversion Therapy, GOLP Regimen, Intrahepatic Cholangiocarcinoma (Icc), TDTP-RECIST
Conditions
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.
Interventions
DRUGGOLP regimen
PD1 antibody (Toripalimab) combined with GEMOX chemotherapy and Lenvatinib neoadjuvant treatment
PROCEDURESurgery
R0 resection
DIAGNOSTIC_TESTTDTP-RECIST
Treatment selection between continued GOLP therapy and surgical R0 resection based on TDTP-RECIST criteria.
Sponsors
Shanghai Geriatric Medical Center
Shanghai Jiao Tong University Affiliated Sixth People's Hospital
Shanghai 10th People's Hospital
Oriental Hepatobiliary Surgery Hospital Affiliated to Naval Military Medical University
Shanghai Zhongshan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 24 months | the time period from the randomization of the patient to the death event due to any reason |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival | 24 months | From randomization to the occurrence of the following events: disease progression prevents radical surgery; local or distant recurrence; second primary tumor; death due to various causes. |
| Objective response rate | 6 months | The proportion of patients whose tumor volume has decreased to a predetermined value |
| Pathological remission rate | 6 months | the ratio of the estimated active tumor size divided by the tumor bed size |
| R0 Resection Rate | 12 months | Curative Surgery Resection Rate |
| Adverse events | 12 months | the severity of adverse events will be evaluated according to the NCI CTCAE 5.0 standard |
| Recurrence-free survival | 24 months | the time from surgery to disease recurrence or all-cause death |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory markers | 24 months | the relationship between treatment response and clinical factors: carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125), tumor mutation burden (TMB), PD-L1 expression, microsatellite instability (MSI), dynamic changes of PET-CT Standard uptake value, dynamic changes of contrast Ultrasound and MRI |
Countries
China
Contacts
Primary ContactXiao-Yong Huang, MD
Backup ContactGuo-Ming Shi, MD
Outcome results
None listed