Back to resultsTACE Combined With "Target Immune" Therapy for First-line Treatment in the Treatment of Intrahepatic Cholangiocarcinoma
Primary Purpose
Intrahepatic Cholangiocarcinoma
Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Transcatheter arterial chemoembolization
Multi-target Drug Therapy
Immunocheckpoint Inhibitor Therapy
Systemic Intravenous Chemotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Intrahepatic Cholangiocarcinoma focused on measuring Intrahepatic Cholangiocarcinoma, Transcatheter arterial chemoembolization, Target therapy, Immune therapy, Systemic Intravenous 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Transcatheter arterial chemoembolization Combined With "Target Immune" Therapy
Traditional Systemic Intravenous Chemotherapy Group
Arm Description
Transcatheter arterial chemoembolization combined with immune checkpoint inhibitors and multi-target drugs was used for treatment.
Traditional systemic intravenous chemotherapy with GEMOX regimen was used for comparison.
Outcomes
Primary Outcome Measures
Progression-free Survival
The most common primary endpoint in cancer trials. The 6 months, 1 year, and 2 years progression-free survival
Secondary Outcome Measures
Overall Survival
The best efficacy endpoint in cancer clinical trials.
Time To Tumor Untreatable Progression
End point of antitumor drug trial.
Objective Response Rate
Evaluation index of clinical efficacy of anticancer drugs.
Disease Control Rate
Evaluation index of clinical efficacy of anticancer drugs.
Duration of Overall Response
Evaluation index of clinical efficacy of anticancer drugs.
The incidence of adverse events and serious adverse events
According to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Full Information
NCT ID
NCT05247996
First Posted
January 24, 2022
Last Updated
February 17, 2022
Sponsor
The Central Hospital of Lishui City
1. Study Identification
Unique Protocol Identification Number
NCT05247996
Brief Title
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
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
March 1, 2022 (Anticipated)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Central Hospital of Lishui City
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intrahepatic Cholangiocarcinoma
Keywords
Intrahepatic Cholangiocarcinoma, Transcatheter arterial chemoembolization, Target therapy, Immune therapy, Systemic Intravenous Chemotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Masking Description
This study is an open-label study. The participants and investigators are not blinded, but the outcomes assessor are blinded.
Allocation
Non-Randomized
Enrollment
98 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Transcatheter arterial chemoembolization Combined With "Target Immune" Therapy
Arm Type
Experimental
Arm Description
Transcatheter arterial chemoembolization combined with immune checkpoint inhibitors and multi-target drugs was used for treatment.
Arm Title
Traditional Systemic Intravenous Chemotherapy Group
Arm Type
Active Comparator
Arm Description
Traditional systemic intravenous chemotherapy with GEMOX regimen was used for comparison.
Intervention Type
Procedure
Intervention Name(s)
Transcatheter arterial chemoembolization
Other Intervention Name(s)
TACE Thrapy
Intervention Description
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
Drug
Intervention Name(s)
Multi-target Drug Therapy
Other Intervention Name(s)
Target Therapy
Intervention Description
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
Intervention Name(s)
Immunocheckpoint Inhibitor Therapy
Other Intervention Name(s)
Immune Therapy
Intervention Description
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
Procedure
Intervention Name(s)
Systemic Intravenous Chemotherapy
Other Intervention Name(s)
Traditional Chemotherapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Progression-free Survival
Description
The most common primary endpoint in cancer trials. The 6 months, 1 year, and 2 years progression-free survival
Time Frame
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 Measure Information:
Title
Overall Survival
Description
The best efficacy endpoint in cancer clinical trials.
Time Frame
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.
Title
Time To Tumor Untreatable Progression
Description
End point of antitumor drug trial.
Time Frame
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.
Title
Objective Response Rate
Description
Evaluation index of clinical efficacy of anticancer drugs.
Time Frame
Proportion of patients who achieved complete remission (CR) or partial remission (PR) according to mRECIST criteria, assessed up to 12 months.
Title
Disease Control Rate
Description
Evaluation index of clinical efficacy of anticancer drugs.
Time Frame
Proportion of patients with complete remission (CR), partial remission (PR), and stable disease (SD) according to mRECIST criteria, assessed up to 12 months.
Title
Duration of Overall Response
Description
Evaluation index of clinical efficacy of anticancer drugs.
Time Frame
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.
Title
The incidence of adverse events and serious adverse events
Description
According to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Time Frame
The time from randomization to every follow-up time, assessed up to 2 years.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jianfei Tu, Dr.
Phone
+8613646782878
Email
jianfei1133@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xihui Ying, MD.
Organizational Affiliation
The Central Hospital of Lishui City
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Citations:
PubMed Identifier
31954497
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.
Results Reference
background
PubMed Identifier
18987916
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.
Results Reference
background
PubMed Identifier
34266407
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.
Results Reference
background
PubMed Identifier
33194055
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.
Results Reference
background
PubMed Identifier
32368294
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.
Results Reference
background
Learn more about this trial
TACE Combined With "Target Immune" Therapy for First-line Treatment in the Treatment of Intrahepatic Cholangiocarcinoma
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