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Combined Therapy Using D-TACE, Gemcitabine and Cisplatin, and PD1 Antibody in Advanced and Unresectable Intrahepatic Cholangiocarcinoma

Primary Purpose

Unresectable Intrahepatic Cholangiocarcinoma

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Camrelizumab
Gemcitabine Injection
Cisplatin injection
Cisplatin-Eluting Beads
D-TACE
Sponsored by
Hua Li
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Unresectable Intrahepatic Cholangiocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age ≥ 18 years old, male or female; Histopathologically confirmed intrahepatic cholangiocarcinoma; Tumor is unresectable assessed by the expert group (R0 resection CANNOT be achieved) and the life expectancy is more than 3 months; Presence of at least one measurable lesion assessed using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST version 1.1); Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Child-Pugh score ≤ 7; Adequate organ function (neutrophil count of ≥1.5×10^9 cells/L, hemoglobin concentrations of ≥90 g/L, platelet cell count of ≥100×10^9 cells/L, bilirubin ≤1.5×ULN, Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 5×ULN, serum creatinine ≤ 1.5 x ULN, Thyroid stimulating hormone (TSH) ≤ 1 x ULN; The patient must be required to sign an informed consent form; Exclusion Criteria: Patients who have received previous treatment with interventional therapy, radiotherapy, ablation, chemotherapy, targeted therapy, immunotherapy (PD-1, PD-L1, CLTA-4 antibody, etc), or surgery within the last 2 months; Patients with other malignant tumors within the last 5 years, except for cured non-melanoma skin cancer, cervical carcinoma in situ, and papillary thyroid carcinoma; Active tuberculosis infection. Patients with active tuberculosis infection within 1 year prior to enrollment; had a history of active tuberculosis infection more than 1 year before enrollment, did not receive formal anti-tuberculosis treatment or tuberculosis is still active; Active infection requiring systemic therapy; Human immunodeficiency virus (HIV) positive; Have an active, known, or suspected autoimmune disease. Subjects who require only hormone replacement therapy for hypothyroidism and skin diseases that do not require systemic therapy may be enrolled; Suffering from high blood pressure, and can not be well controlled by antihypertensive drugs (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg); Abnormal blood coagulation (INR >1.5, or PT>ULN+4s, or APTT >1.5 x ULN), with a bleeding tendency or receiving thrombolytic or anticoagulant therapy; Pregnant or lactating women; Participated in other trials within the last 4 weeks; Has a history of allergy to platinum; Other factors that may influence the safety of the subject or the compliance of the test by the investigator. Serious illnesses (including mental illness), severe laboratory tests, or other family or social factors that require combined treatment.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Combined Therapy Using D-TACE, Gemcitabine and Cisplatin, and Camrelizumab

    Arm Description

    D-TACE with cisplatin-eluting beads. More TACE can be done if clinically necessary. Camrelizumab (200 mg, Intravenous drips (ivd), D1/3W) plus Gem (1000 mg/m2, ivd, D1&8/3W) and Cis (25 mg/m2, ivd, D1&8/3W). Three weeks are one cycle of treatment. Chemotherapy lasted for no more than 12 cycles.

    Outcomes

    Primary Outcome Measures

    Conversion rate
    Rate of unresectable ICC convert to resectable in combination therapy

    Secondary Outcome Measures

    Incidence of adverse events
    Rate of participants with treatment-related adverse events as assessed by CTCAE v4.0
    Objective Response Rate (ORR)
    ORR according to RECIST 1.1 using investigator assessment
    Deepness of response (DpR)
    DpR according to RECIST 1.1 using investigator assessment
    Disease control rate (DCR)
    DCR according to RECIST 1.1 using investigator assessment
    Rate of R0 resection
    R0 resection is defined as no tumor remains at the cutting edge and no tumor cells remain at the cutting edge under the microscope
    Overall Survival (OS)
    OS is defined as the time from date of combined theray start to the date of death from any cause or to the date of last follow-up if patients are alive.
    Progression-free Survival (PFS)
    From the beginning date of combined therapy to the date of disease progression. PFS according to RECIST 1.1 using investigator assessment
    Recurrence-free Survival (RFS)
    RFS is defined as the time between the date of surgery and the date of disease recurrence or death, whichever occurred first. RFS according to RECIST 1.1 using investigator assessment

    Full Information

    First Posted
    February 14, 2023
    Last Updated
    April 19, 2023
    Sponsor
    Hua Li
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05738057
    Brief Title
    Combined Therapy Using D-TACE, Gemcitabine and Cisplatin, and PD1 Antibody in Advanced and Unresectable Intrahepatic Cholangiocarcinoma
    Official Title
    Combined Therapy Using D-TACE, Gemcitabine and Cisplatin Chemotherapy, and PD1 Antibody for Patients With Advanced and Unresectable Intrahepatic Cholangiocarcinoma: a Single-center, Single-arm Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    June 1, 2023 (Anticipated)
    Primary Completion Date
    March 1, 2025 (Anticipated)
    Study Completion Date
    March 1, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Hua Li

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No

    5. Study Description

    Brief Summary
    The goal of this clinical trial is to learn about the combined therapy using drug-eluting bead-transarterial chemoembolization (D-TACE), gemcitabine (Gem) and cisplatin (Cis) chemotherapy, and PD-1 antibody in patients with advanced and unresectable intrahepatic cholangiocarcinoma (ICC). The main questions it aims to answer are: Whether combined therapy using D-TACE, Gem/Cis, and PD-1 works well to convert unresectable ICC to resectable. Whether combined therapy using D-TACE, Gem/Cis, and PD-1 is safe. Participants will receive D-TACE (CalliSpheres with Gem 30 mg), camrelizumab (200 mg) plus gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2), and 24 months follow-up.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Unresectable Intrahepatic Cholangiocarcinoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    22 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Combined Therapy Using D-TACE, Gemcitabine and Cisplatin, and Camrelizumab
    Arm Type
    Experimental
    Arm Description
    D-TACE with cisplatin-eluting beads. More TACE can be done if clinically necessary. Camrelizumab (200 mg, Intravenous drips (ivd), D1/3W) plus Gem (1000 mg/m2, ivd, D1&8/3W) and Cis (25 mg/m2, ivd, D1&8/3W). Three weeks are one cycle of treatment. Chemotherapy lasted for no more than 12 cycles.
    Intervention Type
    Drug
    Intervention Name(s)
    Camrelizumab
    Intervention Description
    200mg on day1 of every 3 weeks, starting on day1 of cycle1
    Intervention Type
    Drug
    Intervention Name(s)
    Gemcitabine Injection
    Intervention Description
    1000mg/m2 on day1 & day8 of every 3 weeks, starting on day1 of cycle 1
    Intervention Type
    Drug
    Intervention Name(s)
    Cisplatin injection
    Intervention Description
    25mg/m2 on day1 & day8 of every 3 weeks, starting on day1 of cycle 1
    Intervention Type
    Drug
    Intervention Name(s)
    Cisplatin-Eluting Beads
    Intervention Description
    used for D-TACE
    Intervention Type
    Procedure
    Intervention Name(s)
    D-TACE
    Intervention Description
    TACE with Cisplatin-Eluting Beads (with Cis 30mg). More TACE can be done if clinically necessary.
    Primary Outcome Measure Information:
    Title
    Conversion rate
    Description
    Rate of unresectable ICC convert to resectable in combination therapy
    Time Frame
    12 months
    Secondary Outcome Measure Information:
    Title
    Incidence of adverse events
    Description
    Rate of participants with treatment-related adverse events as assessed by CTCAE v4.0
    Time Frame
    12 months
    Title
    Objective Response Rate (ORR)
    Description
    ORR according to RECIST 1.1 using investigator assessment
    Time Frame
    12 months
    Title
    Deepness of response (DpR)
    Description
    DpR according to RECIST 1.1 using investigator assessment
    Time Frame
    12 months
    Title
    Disease control rate (DCR)
    Description
    DCR according to RECIST 1.1 using investigator assessment
    Time Frame
    12 months
    Title
    Rate of R0 resection
    Description
    R0 resection is defined as no tumor remains at the cutting edge and no tumor cells remain at the cutting edge under the microscope
    Time Frame
    12 months
    Title
    Overall Survival (OS)
    Description
    OS is defined as the time from date of combined theray start to the date of death from any cause or to the date of last follow-up if patients are alive.
    Time Frame
    12 months
    Title
    Progression-free Survival (PFS)
    Description
    From the beginning date of combined therapy to the date of disease progression. PFS according to RECIST 1.1 using investigator assessment
    Time Frame
    12 months
    Title
    Recurrence-free Survival (RFS)
    Description
    RFS is defined as the time between the date of surgery and the date of disease recurrence or death, whichever occurred first. RFS according to RECIST 1.1 using investigator assessment
    Time Frame
    12 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age ≥ 18 years old, male or female; Histopathologically confirmed intrahepatic cholangiocarcinoma; Tumor is unresectable assessed by the expert group (R0 resection CANNOT be achieved) and the life expectancy is more than 3 months; Presence of at least one measurable lesion assessed using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST version 1.1); Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Child-Pugh score ≤ 7; Adequate organ function (neutrophil count of ≥1.5×10^9 cells/L, hemoglobin concentrations of ≥90 g/L, platelet cell count of ≥100×10^9 cells/L, bilirubin ≤1.5×ULN, Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 5×ULN, serum creatinine ≤ 1.5 x ULN, Thyroid stimulating hormone (TSH) ≤ 1 x ULN; The patient must be required to sign an informed consent form; Exclusion Criteria: Patients who have received previous treatment with interventional therapy, radiotherapy, ablation, chemotherapy, targeted therapy, immunotherapy (PD-1, PD-L1, CLTA-4 antibody, etc), or surgery within the last 2 months; Patients with other malignant tumors within the last 5 years, except for cured non-melanoma skin cancer, cervical carcinoma in situ, and papillary thyroid carcinoma; Active tuberculosis infection. Patients with active tuberculosis infection within 1 year prior to enrollment; had a history of active tuberculosis infection more than 1 year before enrollment, did not receive formal anti-tuberculosis treatment or tuberculosis is still active; Active infection requiring systemic therapy; Human immunodeficiency virus (HIV) positive; Have an active, known, or suspected autoimmune disease. Subjects who require only hormone replacement therapy for hypothyroidism and skin diseases that do not require systemic therapy may be enrolled; Suffering from high blood pressure, and can not be well controlled by antihypertensive drugs (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg); Abnormal blood coagulation (INR >1.5, or PT>ULN+4s, or APTT >1.5 x ULN), with a bleeding tendency or receiving thrombolytic or anticoagulant therapy; Pregnant or lactating women; Participated in other trials within the last 4 weeks; Has a history of allergy to platinum; Other factors that may influence the safety of the subject or the compliance of the test by the investigator. Serious illnesses (including mental illness), severe laboratory tests, or other family or social factors that require combined treatment.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Hua Li, MD&PhD
    Phone
    +8613060975202
    Email
    lihua100@yeah.net
    First Name & Middle Initial & Last Name or Official Title & Degree
    Linsen Ye, MD&PhD
    Phone
    +8618520788663
    Email
    ye_linsen@163.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Yang Yang, MD&PhD
    Organizational Affiliation
    Third Affiliated Hospital, Sun Yat-Sen University
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

    Learn more about this trial

    Combined Therapy Using D-TACE, Gemcitabine and Cisplatin, and PD1 Antibody in Advanced and Unresectable Intrahepatic Cholangiocarcinoma

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