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

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

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Intrahepatic Cholangiocarcinoma
• Intervention / Treatment: Procedure: Transcatheter arterial chemoembolization; Drug: Multi-target Drug Therapy; Drug: Immunocheckpoint Inhibitor Therapy; Procedure: Systemic Intravenous Chemotherapy

Detailed Description

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
• Enrollment (Anticipated): 98
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Transcatheter arterial chemoembolization Combined With "Target Immune" Therapy; Transcatheter arterial chemoembolization combined with immune checkpoint inhibitors and multi-target drugs was used for treatment.	Procedure: Transcatheter arterial chemoembolization; 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.; Other Names: TACE Thrapy; Drug: Multi-target Drug Therapy; 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.; Other Names: Target Therapy; Drug: Immunocheckpoint Inhibitor Therapy; 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.; Other Names: Immune Therapy
ACTIVE_COMPARATOR: Traditional Systemic Intravenous Chemotherapy Group; Traditional systemic intravenous chemotherapy with GEMOX regimen was used for comparison.	Procedure: Systemic Intravenous Chemotherapy; 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.; Other Names: Traditional Chemotherapy

What is the study measuring?

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
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.
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.
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.

Collaborators and Investigators

• Sponsor: The Central Hospital of Lishui City

Publications and helpful links

General Publications

• Kelley RK, Bridgewater J, Gores GJ, Zhu AX. Systemic therapies for intrahepatic cholangiocarcinoma. J Hepatol. 2020 Feb;72(2):353-363. doi: 10.1016/j.jhep.2019.10.009.
• Nathan H, Aloia TA, Vauthey JN, Abdalla EK, Zhu AX, Schulick RD, Choti MA, Pawlik TM. A proposed staging system for intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2009 Jan;16(1):14-22. doi: 10.1245/s10434-008-0180-z. Epub 2008 Nov 6.
• Zou L, Li X, Wu X, Cui J, Cui X, Song X, Ren T, Han X, Zhu Y, Li H, Wu W, Wang X, Gong W, Wang L, Li M, Lau WY, Liu Y. Modified FOLFIRINOX versus gemcitabine plus oxaliplatin as first-line chemotherapy for patients with locally advanced or metastatic cholangiocarcinoma: a retrospective comparative study. BMC Cancer. 2021 Jul 16;21(1):818. doi: 10.1186/s12885-021-08549-2.
• Hu Y, Hao M, Chen Q, Chen Z, Lin H. Comparison of the efficacy and safety among apatinib plus drug-eluting bead transarterial chemoembolization (TACE), apatinib plus conventional TACE and apatinib alone in advanced intrahepatic cholangiocarcinoma. Am J Transl Res. 2020 Oct 15;12(10):6584-6598. eCollection 2020.
• Wang L, Lin ZG, Ke Q, Lou JY, Zheng SG, Bi XY, Wang JM, Guo W, Li FY, Wang J, Zheng YM, Li JD, Cheng S, Zhou WP, Zeng YY. Adjuvant transarterial chemoembolization following radical resection for intrahepatic cholangiocarcinoma: A multi-center retrospective study. J Cancer. 2020 Apr 7;11(14):4115-4122. doi: 10.7150/jca.40358. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 1, 2022
• Primary Completion (ANTICIPATED): December 31, 2022
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: January 24, 2022
• First Submitted That Met QC Criteria: February 17, 2022
• First Posted (ACTUAL): February 21, 2022

Study Record Updates

• Last Update Posted (ACTUAL): February 21, 2022
• Last Update Submitted That Met QC Criteria: February 17, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Immune therapy; Intrahepatic Cholangiocarcinoma; Target therapy; Transcatheter arterial chemoembolization; Systemic Intravenous Chemotherapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma
• Other Study ID Numbers: ZJLS-KLDMIR-22003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Statistical analysis plan, informed consent form, and clinical study report can be shared with other researchers.
• IPD Sharing Time Frame: Within six months after the trial is completed.
• IPD Sharing Access Criteria: Shared data is not available for downloading, but can only be browsed. To download the data, you must contact the researchers. Shared data does not provide any private information of the participants.
• IPD Sharing Supporting Information Type: SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No