A randomized controlled, multicenter, open, seamless phase II-III clinical trial is designed to target patients with resectable intrahepatic cholangiocarcinoma with high-risk recurrence factors which has extremely low postoperative recurrence-free survival. In this study, we aim to compare the prognosis in intrahepatic cholangiocarcinoma between Toripalimab combined with leventinib and GEMOX neoadjuvant treatment and the current clinical surgical treatment (traditional group).
Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor of biliary epithelial cells that originates from the branches of the intrahepatic bile duct at the second level and above. Its incidence accounts for about 15%-20% of primary liver malignancies, showing a gradual increase trend. Surgical resection is currently the main method for the treatment of ICC. The data of a large number of ICC cases shows that even radical resection (R0) patients have an average survival of only 18.3 months, while for palliative resection patients, the average survival is only 6.6 months, and laparotomy patients only 5.6 months. Retrospective studies reported that positive resection margins, lymph node metastasis, lymphatic vessel invasion, nerve bundle invasion, preoperative CA199\>200U/ml, multiple tumor nodules and differentiation are the main factors affecting the survival of ICC patients after surgery. How to improve the surgical results of ICC patients, especially those with high risk factors for postoperative recurrence, is an important way to improve the overall survival of ICC. Neoadjuvant therapy refers to some treatments taken before surgery for newly treated tumor patients who have not found distant metastasis, including chemotherapy, radiotherapy, targeted therapy, etc., to reduce tumor size, reduce tumor stages, and reduce postoperative recurrence rate, prolonging survival time. Our previous study using Toripalimab combined with lenvatinib and Gemox chemotherapy in the first-line treatment of unresectable advanced cholangiocarcinoma (NCT03951597,2020ESMO) showed that the ORR was 80% and the DCR reached 93.3%, of which 1 case was CR, 23 cases were PR, and 2 cases were successfully treated with radical resection after downstage. And the adverse reactions are controllable. These data suggest that Toripalimab combined with lenvatinib and Gemox chemotherapy may be an ideal neoadjuvant treatment for patients with resectable intrahepatic cholangiocarcinoma with high-risk recurrence factors, needing more investigation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
178
PD1 antibody (Toripalimab) combined with GEMOX chemotherapy and Lenvatinib neoadjuvant treatment
Zhongshan hospital
Shanghai, Shanghai Municipality, China
Event-free survival
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.
Time frame: 24 months
Overall survival
the time period from the randomization of the patient to the death event due to any reason
Time frame: 24 months
Objective response rate
The proportion of patients whose tumor volume has decreased to a predetermined value
Time frame: 6 months
Pathological remission rate
the ratio of the estimated active tumor size divided by the tumor bed size
Time frame: 6 months
Adverse events
the severity of adverse events will be evaluated according to the NCI CTCAE 5.0 standard
Time frame: 12 months
R0 Resection Rate
Curative Surgery Resection Rate
Time frame: 12 months
Recurrence-free survival
the time from surgery to disease recurrence or all-cause death
Time frame: 24 months
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