search
Back to results

Hepatic Arterial Infusion Chemotherapy in Combination With Atezolizumab and Bevacizumab for Second-line Treatment of Patients With Recurrent Liver Cancer After Liver Transplantation

Primary Purpose

Recurrent Liver Cancer After Liver Transplantation

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Hepatic arterial infusion chemotherapy + Atezolizumab and bevacizumab
Sponsored by
Shuhong Yi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Liver Cancer After Liver Transplantation focused on measuring Atezolizumab, Bevacizumab, Hepatic arterial infusion chemotherapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age ≥18 years old, ≤75 years old, gender unlimited; hepatocellular carcinoma confirmed by pathology after liver transplantation; CT and/or MRI confirmed tumor recurrence or metastasis, intrahepatic recurrence and extrahepatic metastasis were not suitable for surgical resection; There is at least one measurable recurrent or metastatic tumor lesion; The expected survival time is more than 3 months; Child-Pugh grade A and B (≤7 points); Function of other vital organs: absolute neutrophil count ≥1.5×10E9/L; Platelet ≥50×10 e9 / L; Hemoglobin ≥9 g/dL; Serum albumin ≥2.8g/dL; Thyroid stimulating hormone (TSH)≤1 ULN(if TSH is abnormal, both T3 and T4 levels should be checked. If the levels of T3 and T4 were normal, the patients could be enrolled); Bilirubin ≤ 1.5x ULN; ALT and AST≤3 times ULN; Serum creatinine ≤1.5 ULN; ECOG scored 0-2 points; The patient fully understands and voluntarily signs the informed consent, and is willing and able to comply with the requirements of visit, treatment plan, laboratory examination and other requirements of the study schedule. Exclusion Criteria: Positive expression of PD-L1 in immunohistochemical liver biopsy (parenchymal or non-parenchymal cells of liver); Allergic to bevacizumab and Atezolizumab; ≥ grade II myocardial ischemia or myocardial infarction; The hypertensive drugs cannot be controlled to the normal level (systolic blood pressure > 140mmHg, diastolic blood pressure > 90mmHg); Abnormal coagulation function (PT>16s, APTT>43s, TT>21s, Fbg <2g/L), a history of gastrointestinal bleeding within 6 months; Patients with high risk of bleeding or receiving thrombolytic or anticoagulant treatment; Autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, psoriasis, etc.; The primary liver disease of liver transplantation was autoimmune hepatitis, primary biliary cirrhosis, or primary sclerosing cholangitis; interstitial pneumonia and other lung diseases, poor lung function; Participate in clinical trials of other experimental drugs within 4 weeks; infections requiring systemic treatment; human immunodeficiency virus (HIV) positive infection; Other factors that may affect safety or compliance; During treatment of acute rejection or within 1 month after treatment; Poor compliance.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Hepatic arterial infusion chemotherapy + Atezolizumab and bevacizumab

    Arm Description

    Hepatic arterial infusion chemotherapy: percutaneous introduction of a standard hepatic arterial catheter through the femoral artery. FOLFOX was sequentially transfused by a fixed catheter. Drugs:FOLFOX regimen: oxaliplatin, calcium folinate, and 5-FU. Atezolizumab: About 3 to 7 days after HAIC treatment, when liver function is stable (TBILI<2 times the upper limit of normal), Atezolizumab therapy can be started. The dosage was 1200mg and was given intravenously for at least 1 hour, once every 3 weeks. The longest course of treatment is 24 months. Bevacizumab: About 3 to 7 days after HAIC treatment, when liver function is stable (TBILI<2 times the upper limit of normal), bevacizumab therapy can be started. The dosage was 15mg/kg and was given intravenously for no less than 1 hour, once every 3 weeks. The longest course of treatment is 24 months.

    Outcomes

    Primary Outcome Measures

    Acute graft rejection rate
    defined as the incidence of acute graft rejection after HAIC combined with T+A.
    Objective Response Rate
    defined as the treatment response assessed by mRECIST after HAIC combined with T+A treatment

    Secondary Outcome Measures

    Overall Survival
    defined as the time from HAIC combined with T+A treatment to patient death from any cause.
    Progression-free Survival
    defined as the time from the start of HAIC combined with T+A treatment to the onset of tumor Progression or death from any cause.
    Time to Progression
    defined as the time from the start of HAIC combined with T+A treatment to tumor progression or death from any cause.
    Serious Adverse Event
    The incidence of serious adverse events caused by HAIC combined with T+A treatment.
    Graft Rejection
    defined as the incidence of transplant rejection during HAIC combined with T+A treatment.

    Full Information

    First Posted
    March 29, 2023
    Last Updated
    May 30, 2023
    Sponsor
    Shuhong Yi
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT05833126
    Brief Title
    Hepatic Arterial Infusion Chemotherapy in Combination With Atezolizumab and Bevacizumab for Second-line Treatment of Patients With Recurrent Liver Cancer After Liver Transplantation
    Official Title
    Hepatic Arterial Infusion Chemotherapy in Combination With Atezolizumab and Bevacizumab for Second-line Treatment of Patients With Recurrent Liver Cancer After Liver Transplantation: an Open-label, Prospective, Single-center, Single-arm Clinical Study Protocol
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2023
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Ethical approval has not yet been completed
    Study Start Date
    May 1, 2023 (Anticipated)
    Primary Completion Date
    November 1, 2024 (Anticipated)
    Study Completion Date
    April 1, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Shuhong Yi

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    For patients with recurrent liver cancer after liver transplantation, the median survival time is low and the prognosis is often poor. On the one hand, it is necessary to take into account the weakened effect of postoperative anti-rejection drugs with the use of immune checkpoint inhibitors, and on the other hand, the therapeutic effect of recurrent tumors should be taken into account. Both HAIC (hepatic arterial infusion chemotherapy) and T+A(Bevacizumab+Atezolizumab) have inhibitory effects on tumor, and we consider combining them organically to explore one that not only has a good inhibitory effect on tumor, but also better reduces the risk and degree of rejection. Therefore, in order to determine the feasibility and effectiveness of hepatic arterial infusion chemotherapy combined with Atezolizumab and Bevacizumab in the second-line treatment of patients with recurrent liver cancer after liver transplantation

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Recurrent Liver Cancer After Liver Transplantation
    Keywords
    Atezolizumab, Bevacizumab, Hepatic arterial infusion chemotherapy

    7. Study Design

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

    8. Arms, Groups, and Interventions

    Arm Title
    Hepatic arterial infusion chemotherapy + Atezolizumab and bevacizumab
    Arm Type
    Experimental
    Arm Description
    Hepatic arterial infusion chemotherapy: percutaneous introduction of a standard hepatic arterial catheter through the femoral artery. FOLFOX was sequentially transfused by a fixed catheter. Drugs:FOLFOX regimen: oxaliplatin, calcium folinate, and 5-FU. Atezolizumab: About 3 to 7 days after HAIC treatment, when liver function is stable (TBILI<2 times the upper limit of normal), Atezolizumab therapy can be started. The dosage was 1200mg and was given intravenously for at least 1 hour, once every 3 weeks. The longest course of treatment is 24 months. Bevacizumab: About 3 to 7 days after HAIC treatment, when liver function is stable (TBILI<2 times the upper limit of normal), bevacizumab therapy can be started. The dosage was 15mg/kg and was given intravenously for no less than 1 hour, once every 3 weeks. The longest course of treatment is 24 months.
    Intervention Type
    Drug
    Intervention Name(s)
    Hepatic arterial infusion chemotherapy + Atezolizumab and bevacizumab
    Intervention Description
    Drug: Oxaliplatin, calcium folinate, 5-FU, Atezolizumab and bevacizumab Procedure: HAIC
    Primary Outcome Measure Information:
    Title
    Acute graft rejection rate
    Description
    defined as the incidence of acute graft rejection after HAIC combined with T+A.
    Time Frame
    3 months
    Title
    Objective Response Rate
    Description
    defined as the treatment response assessed by mRECIST after HAIC combined with T+A treatment
    Time Frame
    1 year
    Secondary Outcome Measure Information:
    Title
    Overall Survival
    Description
    defined as the time from HAIC combined with T+A treatment to patient death from any cause.
    Time Frame
    1 year
    Title
    Progression-free Survival
    Description
    defined as the time from the start of HAIC combined with T+A treatment to the onset of tumor Progression or death from any cause.
    Time Frame
    1 year
    Title
    Time to Progression
    Description
    defined as the time from the start of HAIC combined with T+A treatment to tumor progression or death from any cause.
    Time Frame
    1 year
    Title
    Serious Adverse Event
    Description
    The incidence of serious adverse events caused by HAIC combined with T+A treatment.
    Time Frame
    1 year
    Title
    Graft Rejection
    Description
    defined as the incidence of transplant rejection during HAIC combined with T+A treatment.
    Time Frame
    1 year

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age ≥18 years old, ≤75 years old, gender unlimited; hepatocellular carcinoma confirmed by pathology after liver transplantation; CT and/or MRI confirmed tumor recurrence or metastasis, intrahepatic recurrence and extrahepatic metastasis were not suitable for surgical resection; There is at least one measurable recurrent or metastatic tumor lesion; The expected survival time is more than 3 months; Child-Pugh grade A and B (≤7 points); Function of other vital organs: absolute neutrophil count ≥1.5×10E9/L; Platelet ≥50×10 e9 / L; Hemoglobin ≥9 g/dL; Serum albumin ≥2.8g/dL; Thyroid stimulating hormone (TSH)≤1 ULN(if TSH is abnormal, both T3 and T4 levels should be checked. If the levels of T3 and T4 were normal, the patients could be enrolled); Bilirubin ≤ 1.5x ULN; ALT and AST≤3 times ULN; Serum creatinine ≤1.5 ULN; ECOG scored 0-2 points; The patient fully understands and voluntarily signs the informed consent, and is willing and able to comply with the requirements of visit, treatment plan, laboratory examination and other requirements of the study schedule. Exclusion Criteria: Positive expression of PD-L1 in immunohistochemical liver biopsy (parenchymal or non-parenchymal cells of liver); Allergic to bevacizumab and Atezolizumab; ≥ grade II myocardial ischemia or myocardial infarction; The hypertensive drugs cannot be controlled to the normal level (systolic blood pressure > 140mmHg, diastolic blood pressure > 90mmHg); Abnormal coagulation function (PT>16s, APTT>43s, TT>21s, Fbg <2g/L), a history of gastrointestinal bleeding within 6 months; Patients with high risk of bleeding or receiving thrombolytic or anticoagulant treatment; Autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, psoriasis, etc.; The primary liver disease of liver transplantation was autoimmune hepatitis, primary biliary cirrhosis, or primary sclerosing cholangitis; interstitial pneumonia and other lung diseases, poor lung function; Participate in clinical trials of other experimental drugs within 4 weeks; infections requiring systemic treatment; human immunodeficiency virus (HIV) positive infection; Other factors that may affect safety or compliance; During treatment of acute rejection or within 1 month after treatment; Poor compliance.

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

    Learn more about this trial

    Hepatic Arterial Infusion Chemotherapy in Combination With Atezolizumab and Bevacizumab for Second-line Treatment of Patients With Recurrent Liver Cancer After Liver Transplantation

    We'll reach out to this number within 24 hrs