Sorafenib Combined With Arsenical in Treating Patients With Recurrent HCC After Liver Transplantation (HCC)

An Exploratory Study Evaluating the Efficacy, Safety, and Pharmacokinetics of Sorafenib Combined With Realgar-Indigo Naturalis Formula (RIF) in in Treating Patients With Recurrent Hepatocellular Carcinoma After Liver Transplantation

To analyze the safety, efficacy and pharmacokinetic characteristics of sorafenib combined with compound huangdai tablets in patients with recurrent hepatocellular carcinoma after liver transplantation

Study Overview

• Status: Unknown
• Conditions: HCC
• Intervention / Treatment: Drug: Arsenicals

Detailed Description

Background: postoperative recurrence after liver transplantation is a global problem, and there is no standard treatment model for postoperative recurrence. Objective: to select patients diagnosed with hepatocellular carcinoma (HCC) after liver transplantation and unable to receive local treatment, and to give sorafenib combined with realgar-indigo naturalis formula until the disease progression or the patient die or is lost to follow-up. To analyze the safety, efficacy and pharmacokinetic characteristics of sorafenib combined with compound huangdai tablets in patients with recurrent hepatocellular carcinoma after liver transplantation

• Study Type: Interventional
• Enrollment (Anticipated): 43
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hangyu Zhang; Phone Number: 0571-87236858; Email: zhanghangyu@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • the First Affiliated Hospital, School of Medicine, Zhejiang University
      • Contact: Liang TingBo, MD, PHD; Phone Number: 086-571-87236688; Email: liangtingbo@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• aged 18-75 (inclusive), male or female;
• recurrence of HCC after liver transplantation;
• grade C according to the Barcelona liver cancer classification criteria (BCLC) or grade B not suitable for local treatment/progression of local treatment
• according to RECIST1.1, there was at least one target lesion that could be stably evaluated, defined as: longest diameter of non-lymph node lesion ≥10mm, or shortest diameter of lymph node lesion ≥15mm; The intrahepatic lesions required enhanced arterial development
• expected survival more than 12 weeks;
• child-pugh score ≤7;
• ECOG score 0-1;
• if the subject is HBsAg positive or HBcAb positive, hbv-dna < 200 IU/ml should be satisfied. HBsAg positive subjects must receive antiviral therapy in accordance with the 2015 guidelines for the prevention and treatment of chronic hepatitis B.
• subject should meet the following test results before screening and pretreatment (at baseline). If abnormal laboratory tests do not meet the following criteria, the subjects are allowed to re-examine within one week. If they still do not meet the criteria, the screening will be considered a failure: A. Blood routine (no blood transfusion, platelet transfusion, cell growth factor (except recombinant erythropoietin) and other supportive treatments should be performed within 7 days before the test) : WBC ≥ 2.5×109/L; Platelet count (PLT) ≥60×109/L; Hemoglobin (Hb) ≥ 9.0g /dL; B. Blood biochemistry: serum albumin (Alb) ≥30 g/L; The clearance rate of endogenous creatinine was ≥50 mL/min (Cockcroft -Gault formula was used). Alanine aminotransferase (ALT) ≤5× upper limit of normal value (ULN); Aspartate aminotransferase (AST) ≤5×ULN; Alkaline phosphatase ≤5×ULN; Total bilirubin ≤2×ULN; C. Prothrombin time (PT) : prothrombin time extension ≤ 4 s;
• women of child-bearing age must undergo a serum pregnancy test within the screening period and 14 days prior to the initiation of the study drug, with negative results, and be willing to use reliable methods of contraception during the test period; Male subjects whose partners are women of child-bearing age should be sterilized or agree to use reliable methods of contraception during the trial;
• be able to understand and sign the informed consent.

Exclusion Criteria:

• participate in other clinical trials or use other research drugs or devices within 4 weeks of the first treatment.
• pregnant or breastfeeding women;
• positive for human immunodeficiency virus (HIV) antibody, treponema pallidum antibody or hepatitis C virus (HCV-RNA) antibody;
• any uncontrolled active infection, including but not limited to subjects with active tuberculosis;
• previous or present hepatic encephalopathy;
• the presence of clinically significant ascites is defined as the ascites that are positive on physical examination or that need to be controlled by intervention therapy (for example, puncture or drug therapy, etc.).
• imaging results: the proportion of liver replaced by tumor was ≥50%, and the main portal vein tumor thrombus or tumor thrombus invaded mesenteric vein/inferior vena cava;
• adverse reactions caused by previous treatment did not return to the standard term for adverse events (CTCAE) ≤1, except hair loss and other tolerable events judged by researchers;
• subjects who currently have unstable or active ulcers, gastrointestinal bleeding, or intolerance to proton pump inhibitors;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sorafenib + arsenical; After enrollment, the patients received oral treatment at sorafenib 200mg bid continuous and realgar-indigo naturalis formula preparation at 60mg/kg tid p.o, d1-14, q4w	Drug: Arsenicals; As4 S4; Other Names: sorafenib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	objective response rate	Through the study peirod, for 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	progression-free survival	Through the study peirod, for 18 months
DCR	disease control rate	Through the study peirod, for 18 months
OS	overall survival	Through the study peirod, for 18 months
Safty	adverse event	Through the study peirod, for 18 months

Collaborators and Investigators

• Sponsor: Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): June 30, 2022

Study Registration Dates

• First Submitted: January 1, 2020
• First Submitted That Met QC Criteria: January 14, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 14, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: CISLD6

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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