Clinical trial NCT05247996: TACE Combined With "Target Immune" Therapy for First-line Treatment in the Treatment of Intrahepatic Cholangiocarcinoma
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Intrahepatic Cholangiocarcinoma
Keywords: Intrahepatic Cholangiocarcinoma
Transcatheter arterial chemoembolization
Target therapy
Immune therapy
Systemic Intravenous Chemotherapy
Lead sponsor: The Central Hospital of Lishui City
Sponsor class: OTHER
First posted: 2022-02-21
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression-free Survival
timeFrame: 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:
measure: Overall Survival
timeFrame: 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.
measure: Time To Tumor Untreatable Progression
timeFrame: 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.
measure: Objective Response Rate
timeFrame: Proportion of patients who achieved complete remission (CR) or partial remission (PR) according to mRECIST criteria, assessed up to 12 months.
measure: Disease Control Rate
timeFrame: Proportion of patients with complete remission (CR), partial remission (PR), and stable disease (SD) according to mRECIST criteria, assessed up to 12 months.
measure: Duration of Overall Response
timeFrame: 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.
measure: The incidence of adverse events and serious adverse events
timeFrame: The time from randomization to every follow-up time, assessed up to 2 years.
Other outcomes:
Locations:
Study officials:
affiliation: The Central Hospital of Lishui City
name: Xihui Ying, MD.
role: STUDY_DIRECTOR
References:
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.
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.
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.
citation: 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.
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.