TACE Combined With Target Immune Therapy for First-line Treatment in the Treatment of Intrahepatic Cholangiocarcinoma

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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TACE Combined With Target Immune Therapy for First-line Treatment Compared With Intravenous Chemotherapy in the Treatment of Unresectable Intrahepatic Cholangiocarcinoma: A Prospective, Multicenter, Open, Real-World Clinical Study

Conditions
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Intrahepatic Cholangiocarcinoma

Intervention / Treatment
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* Procedure: Transcatheter arterial chemoembolization
* Drug: Multi-target Drug Therapy
* Drug: Immunocheckpoint Inhibitor Therapy
* Procedure: Systemic Intravenous Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients shall be older than 18 years old and have no gender limitation; Patients with intrahepatic cholangiocarcinoma confirmed by histopathology or clinical diagnosis and treatment standards who are inoperable or unwilling to undergo surgery at first diagnosis or who cannot be resected after recurrence; Patients with measurable lesions that can be observed and evaluated and whose diameter≥1cm are accurately measured by MRI enhancement or Computed Tomography (CT) enhancement according to mRECIST criteria; Patients with Child-Pugh A or B liver function grade and basically normal heart function; ECOG PS score≤1; Patients with expected survival > 3 months; Patients who have voluntarily participated in the study, signed informed consent, had good compliance, and cooperated with follow-up; There is no active HBV-DNA replication before enrollment (HBV-DNA<2000IU/mL), and HBV-positive patients have received anti-HBV treatment before enrollment. Exclusion Criteria: Pregnant women, breast-feeding women or patients of childbearing age planning; Patients with severe heart, liver, and renal insufficiency and thyroid dysfunction; Patients scheduled for liver transplantation; Patients who have had or are currently suffering from other malignant tumors within five years, except cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumor; Patients with pleural effusion or ascites, causing respiratory syndrome (≥ CTCAE grade 2 dyspnea); Patients with unmitigated toxicity higher than CTCAE level 1 (5.0) due to any prior treatment; Patients with multiple factors affecting oral medication (such as inability to swallow, chronic diarrhea, etc.); Patients with symptoms and signs of interstitial diseases.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transcatheter arterial chemoembolization Combined With Target Immune Therapy<br>Transcatheter arterial chemoembolization combined with immune checkpoint inhibitors and multi-target drugs was used for treatment. | Procedure: Transcatheter arterial chemoembolization<br>* 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.<br>* Other names: TACE Thrapy;Drug: Multi-target Drug Therapy<br>* 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.<br>* Other names: Target Therapy;Drug: Immunocheckpoint Inhibitor Therapy<br>* 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.<br>* Other names: Immune Therapy;|
| Active Comparator: Traditional Systemic Intravenous Chemotherapy Group<br>Traditional systemic intravenous chemotherapy with GEMOX regimen was used for comparison. | Procedure: Systemic Intravenous Chemotherapy<br>* 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.<br>* Other names: Traditional Chemotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | The most common primary endpoint in cancer trials. The 6 months, 1 year, and 2 years progression-free survival | The time from enrollment to tumor progression or death from any cause, whichever came first, measured in months, assessed up to 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | The best efficacy endpoint in cancer clinical trials. | 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. | 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. | 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. | 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. | 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. | The time from randomization to every follow-up time, assessed up to 2 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intrahepatic Cholangiocarcinoma, Transcatheter arterial chemoembolization, Target therapy, Immune therapy, Systemic Intravenous Chemotherapy