Efficacy and Safety of TACE on Downstaging Hepatocellular Carcinoma Beyond UCSF Criteria;

Efficacy and Safety of TACE on Downstaging Hepatocellular Carcinoma Beyond UCSF Criteria: a Multi-center, Randomized, Parallel-controlled Study

This is a multicenter, randomized, parallel controlled study to determine the efficacy and safety of transcatheter arterial chemoembolization (TACE) on downstaging hepatocellular carcinoma beyond University of California, San Francisco (UCSF) criteria.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Procedure: DEB-TACE; Device: Drug-eluting Beads; Drug: Epirubicin; Procedure: cTACE

• Study Type: Interventional
• Enrollment (Anticipated): 226
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jiahong Dong, MD; Phone Number: 01056118763; Email: dongjiahong@mail.tsir

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Tsinghua Chang Gung Hospital
    • Contact: Jiahong Dong; Phone Number: 13240009509

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 to 70 years of age, of any sex;
2. Patients who have histopathological or cytological proof of hepatocellular carcinoma (HCC) or meet the diagnostic criteria of Diagnosis, management, and treatment of hepatocellular carcinoma(V2017);
3. Beyond UCSF criteria: Diameter of single HCC lesion is between 6.5 cm and 10 cm; The number of tumors ≤3 with the maximum diameter of 4.5-5cm and the total diameter ≤10cm; Multiple HCC lesions ≤5 nodules, each lesion diameter≤4 cm with a total diameter ≤10 cm. Patients cannot be treated with resection or liver transplantation;
4. Patients with stage Ib，IIa，IIb in China liver cancer staging (CNLC) ;
5. Child-Pugh's grade A or B (no more than 7 score);
6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-1;
7. Patients with hepatitis B virus (HBV) infection should receive routine antiviral therapy;
8. The function of main organs is normal and meet the following criteria:

1) Outcome of blood routine must meet the following criteria (No blood transfusion or blood products were performed within 4 days, and no g-CSF or other hematopoietic stimulants were used for correction): i. Hemoglobin(HB)≥90 g/L; ii. Absolute neutrophil count (ANC)≥1.5×109/L； iii. Platelet (PLT)≥80×109/L; 2) Outcome of hemal biochemistry examination meet the following criteria: i. Albumin (ALB) ≥29 g/L; ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)<2.5 × upper limit of normal (ULN); iii. Total bilirubin (TBIL) ≤2 × ULN; iv. Serum creatinine (SCr) ≤1.25 × ULN, or endogenous creatinine clearance > 45 ml/min (Cockcroft-Gault formula); 3) Patients who have normal livers with an Remnant Liver Volume (RLV)/Standard Liver Volume(SLV) >20% ; Patients who have cirrhosis with an RLV/SLV>40%; 9. Life expectancy of > 3 months; 10. Patients volunteered to participate in this study and signed informed consent, with good compliance.Exclusion Criteria.

Exclusion Criteria:

1. Patients with extrahepatic metastasis or main portal vein /main hepatic vein invasion;
2. Patients with diffuse liver cancer;
3. Patients with myocardial ischemia, myocardial infarction or poor controlled arrhythmia (including QTc≥470 ms) beyond stage Ⅱ; according to New York Heart Association (NYHA) standard, patients with heart failure in stage Ⅲ～Ⅳ; patients with an left ventricular ejection fraction(LVEF) <50%;
4. Abnormal coagulation （International Normalized Ratio(INR)>1.5, Prothrombin Time(PT)>ULN+4s or Activated Partial Thromboplastin Time (APTT) >1.5 ×ULN）,or patients with bleeding tendency or undergoing thrombolytic or anticoagulant therapy;
5. Patients unsuitable for the study in the opinion of the Investigator;
6. Pregnant or breastfeeding women; women of childbearing ages unless using effective contraception;
7. Patients with mental disorders or history of abuse of psychotropic substances;
8. Infection with human immunodeficiency virus (HIV);
9. A history of liver resection, liver transplantation, interventional therapy, or combined with other malignant tumors;
10. Patients with active infection;
11. Patients with contraindications to TACE or epirubicin;
12. Floating population or with poor compliance;
13. Patients in other clinical trials conducting with experimental-related drugs or devices within 4 weeks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Drug-eluting bead transarterial chemoembolization(DEB-TACE)	Procedure: DEB-TACE; Drug-eluting beads transcatheter arterial chemoembolization; Device: Drug-eluting Beads; Drug-eluting beads; Drug: Epirubicin; Chemotherapy drug for intra-arterial infusion
ACTIVE_COMPARATOR: conventional transarterial chemoembolization(cTACE)	Drug: Epirubicin; Chemotherapy drug for intra-arterial infusion; Procedure: cTACE; Transcatheter arterial chemoembolization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Downstaging success rate	Criteria for success rate in downstaging meet UCSF criteria or the standard for liver resection.	Within 6 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response (CR)	Disappearance of any intratumoral arterial enhancement in all target lesions	1, 3, 6 months after surgery
Partial response (PR)	At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions	1, 3, 6 months after surgery
Stable disease (SD)	Number of the subjects that do not qualify for partial response or progressive disease measured by modified Response Evaluation Criteria in Solid Tumors( mRECIST) criteria	up to 6months after TACE procedure
Progressive disease (PD)	An increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started	1, 3, 6 months after surgery
Objective response (OR)	CR+PR	1, 3, 6 months after surgery
Duration of downstaging	Interval between initial TACE treatment and the success or failure of downstaging according to the UCSF criteria assessed by the dynamic enhanced CT ;	within 36 months
Times of TACE treatments	Times of TACE surgery	within 36 months
Changes of tumor biomarkers (AFP, PIVKA-Ⅱ)	AFP and PIVKA-II must be measured at 1week before, 1 week,1month after TACE or curative treatment; AFP ,PIVKA-II could be measured every 3-6 months during follow up according to the availability of equipment at the site	From 7 days before TACE or curative treatments to the endpoints of the trial.(Up to 36 months)
Changes in liver function	Changes of the Child-pugh Score that used to assess the prognosis of chronic liver disease,consisting of 5 items(ascites,total bilirubin，albumin,prothrombin time and degree of encephalopathy),of which is scored 1-3 points,with 3 indicating greatest severity)	from the date of the first TACE to the end of the clinical trial or the death of the patient，Up to 36months
Tumor-free survival (TFS)	as the time from surgery initiation to tumor recurrence or death from any cause	Within 36 months
Progression-free survival (PFS)	as the time from surgery initiation to disease progression or death from any cause	Within 36 months
Overall survival (OS)	as the time from surgery initiation to death from any cause	Within 36 months
Recurrence rate of Hepatocellular carcinoma	Recurrence rate of hepatocellular carcinoma	Within 36 months

Collaborators and Investigators

• Sponsor: Beijing Tsinghua Chang Gung Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 18, 2020
• Primary Completion (ANTICIPATED): November 1, 2022
• Study Completion (ANTICIPATED): December 1, 2025

Study Registration Dates

• First Submitted: November 23, 2020
• First Submitted That Met QC Criteria: February 3, 2021
• First Posted (ACTUAL): February 4, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 4, 2021
• Last Update Submitted That Met QC Criteria: February 3, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Epirubicin
• Other Study ID Numbers: 19229-0-02

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