This study is a prospective, multicenter, open, real-world clinical study. All eligible patients were assigned to experimental group (TACE combined with multi-target drugs and PD-1 inhibitors), and control group (conventional intravenous chemotherapy), to explore the efficacy and safety of TACE combined with multi-target drugs and PD-1 inhibitors as first-line treatment compared with traditional systemic intravenous chemotherapy in the treatment of unresectable intrahepatic cholangiocarcinoma (ICC).
This study is a prospective, multi-center, open, and double-arm clinical study in the real world, which belongs to a practical clinical trial. The type of comparison is the non-inferiority test. This study enrolls 98 patients with unresectable intrahepatic cholangiocarcinoma at multiple centers across the country. In the experimental group, 49 patients will receive TACE combined with immune checkpoint inhibitors and multi-target drugs; In the control group, 49 patients will receive traditional systemic intravenous chemotherapy with GEMOX regimen.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
98
Treatment regimens have chosen "lipiodol-based" hepatic arterial chemoembolization, with lipiodol dosage varying from 5-20ml depending on tumor size. The chemotherapy drug is gemcitabine 1.0 combined with 100mg oxaliplatin, combined with 1/3 to 1 dose of solid embolic agent (the dosage is determined by the investigator based on the tumor size). After uniform emulsification, the drug is injected into the supplying blood vessels and stops when the intravascular blood flow is slow. Later, angiography is performed again, and the tumor staining disappears and the supplying artery is occlusions. CT or MRI scans are performed 4 to 6 weeks postoperatively to assess the presence of active lesions. Repeat TACE if active lesions are still present. The frequency of TACE treatment is determined by the investigator and is given according to the patient's condition, generally 2-4 times. The interval between TACE treatments is 30-45 days, with a maximum of six cycles.
Multi-target drugs (lenvatinib or donafenib) are selected at the patient's preference. Oral multitarget drugs are initiated 3-7 days after initial TACE treatment until tumor progression is assessed. The initial dose of lenvatinib is 8mg/ day (bodyweight \< 60 kg) or 12 mg/ day (body weight≥60 kg); Donafenil 0.2g, twice a day, taken orally on an empty stomach. If the medication is missed, there is no need to take a refill and the next dose shall be taken at the usual time.
Optional types of immune checkpoint inhibitors include Sintilimab injection and Tislelizumab injection. Treatment shall be based on the immune checkpoint inhibitors before enrollment, and it is not recommended to change the immune checkpoint inhibitors; Dosage: 200mg, iv, D1, every 21 days (Q3W), continuous until tumor progression.
GEMOX regimen (gemcitabine 1000mg/m2, oxaliplatin 100mg/m2) is given for systemic intravenous chemotherapy after the exclusion of contraindications for chemotherapy, and the presence of active lesions is assessed by laboratory and imaging examinations after every two courses of treatment. If active lesions remain, repeated systemic intravenous chemotherapy may be performed. The frequency of chemotherapy is determined by the investigator and is given according to the needs of the patient, usually 6 times with an interval of 21-28 days.
Progression-free Survival
The most common primary endpoint in cancer trials. The 6 months, 1 year, and 2 years progression-free survival
Time frame: The time from enrollment to tumor progression or death from any cause, whichever came first, measured in "months", assessed up to 2 years.
Overall Survival
The best efficacy endpoint in cancer clinical trials.
Time frame: Time from randomization to death from any cause, in "months", assessed up to 2 years. For patients who are still alive at the time of data analysis, OS is calculated based on the date when the patient is last known to be alive.
Time To Tumor Untreatable Progression
End point of antitumor drug trial.
Time frame: The time interval between receiving TACE or intravenous chemotherapy and the patient's inability to receive further intra-arterial treatment, assessed up to 12 months.
Objective Response Rate
Evaluation index of clinical efficacy of anticancer drugs.
Time frame: Proportion of patients who achieved complete remission (CR) or partial remission (PR) according to mRECIST criteria, assessed up to 12 months.
Disease Control Rate
Evaluation index of clinical efficacy of anticancer drugs.
Time frame: Proportion of patients with complete remission (CR), partial remission (PR), and stable disease (SD) according to mRECIST criteria, assessed up to 12 months.
Duration of Overall Response
Evaluation index of clinical efficacy of anticancer drugs.
Time frame: The time from the first assessment of the tumor as complete remission or partial remission to the first assessment as disease progression or death from any cause, assessed up to 12 months.
The incidence of adverse events and serious adverse events
According to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Time frame: The time from randomization to every follow-up time, assessed up to 2 years.
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