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

Intrahepatic Cholangiocarcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05247996
• Other study ID #: ZJLS-KLDMIR-22003
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 1, 2022
• Est. completion date: December 31, 2023

Study information

• Verified date: January 2022
• Source: The Central Hospital of Lishui City
• Contact: Jianfei Tu, Dr.
• Phone: +8613646782878
• Email: jianfei1133[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 98
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Intrahepatic Cholangiocarcinoma

Intervention

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.

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.
• 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.

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
The Central Hospital of Lishui City

References & Publications (5)

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.