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

NCT05247996 | Unknown

• 1 other identifier: ZJLS-KLDMIR-22003
• Study Type: interventional
• Target: 98
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Intrahepatic Cholangiocarcinoma

Keywords

Intrahepatic Cholangiocarcinoma; Transcatheter arterial chemoembolization; Target therapy; Immune therapy; Systemic Intravenous Chemotherapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Overall Survival

  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

  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

  Proportion of patients who achieved complete remission (CR) or partial remission (PR) according to mRECIST criteria, assessed up to 12 months.

• Disease Control Rate

  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

  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.

Study Arms (2)

Transcatheter arterial chemoembolization Combined With "Target Immune" Therapy

EXPERIMENTAL

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

Procedure: Transcatheter arterial chemoembolization; Drug: Multi-target Drug Therapy; Drug: Immunocheckpoint Inhibitor Therapy

Traditional Systemic Intravenous Chemotherapy Group

ACTIVE COMPARATOR

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

Procedure: Systemic Intravenous Chemotherapy

Interventions

Transcatheter arterial chemoembolization 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.

Also known as: TACE Thrapy

Transcatheter arterial chemoembolization Combined With "Target Immune" Therapy

Multi-target Drug Therapy 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.

Also known as: Target Therapy

Transcatheter arterial chemoembolization Combined With "Target Immune" Therapy

Immunocheckpoint Inhibitor Therapy 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.

Also known as: Immune Therapy

Transcatheter arterial chemoembolization Combined With "Target Immune" Therapy

Systemic Intravenous Chemotherapy 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.

Also known as: Traditional Chemotherapy

Traditional Systemic Intravenous Chemotherapy Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Central Hospital of Lishui City: lead

Related Publications (5)

• 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.

  PMID: 31954497 BACKGROUND

• 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.

  PMID: 18987916 BACKGROUND

• 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.

  PMID: 34266407 BACKGROUND

• 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.

  PMID: 33194055 BACKGROUND

• 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.

  PMID: 32368294 BACKGROUND

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

Immunotherapy, Active

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Xihui Ying, MD.

  The Central Hospital of Lishui City

  STUDY DIRECTOR

Central Study Contacts

Jianfei Tu, Dr.

CONTACT

+8613646782878; jianfei1133@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: This study is an open-label study. The participants and investigators are not blinded, but the outcomes assessor are blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2022
• First Posted: February 21, 2022
• Study Start: March 1, 2022
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2023
• Last Updated: February 21, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ICF, CSR
• Time Frame: Within six months after the trial is completed.
• 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.