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

NCT ID: NCT05247996

Last Updated: 2022-02-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-01
• Study Completion Date: 2023-12-31

Brief 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).

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.

Conditions

Intrahepatic Cholangiocarcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Transcatheter arterial chemoembolization Combined With "Target Immune" Therapy

Transcatheter arterial chemoembolization combined with immune checkpoint inhibitors and multi-target drugs was used for treatment.

Group Type: EXPERIMENTAL

Transcatheter arterial chemoembolization

Intervention Type: PROCEDURE

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 Drug Therapy

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Traditional Systemic Intravenous Chemotherapy Group

Traditional systemic intravenous chemotherapy with GEMOX regimen was used for comparison.

Group Type: ACTIVE_COMPARATOR

Systemic Intravenous Chemotherapy

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: PROCEDURE

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.

Intervention Type: 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.

Intervention Type: DRUG

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.

Intervention Type: PROCEDURE

Other Intervention Names

TACE Thrapy; Target Therapy; Immune Therapy; Traditional Chemotherapy

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Central Hospital of Lishui City

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xihui Ying, MD.

Role: STUDY_DIRECTOR

The Central Hospital of Lishui City

Central Contacts

Jianfei Tu, Dr.

Role: CONTACT

jianfei1133@163.com

+8613646782878

References

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.

Reference Type: BACKGROUND

PMID: 31954497 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18987916 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34266407 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33194055 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32368294 (View on PubMed)

Other Identifiers

ZJLS-KLDMIR-22003

Identifier Type: -

Identifier Source: org_study_id