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

• ClinicalTrials.gov Identifier: NCT04738188
• Recruitment Status: Recruiting
• First Posted: February 4, 2021
• Last Update Posted: February 4, 2021
• Sponsor: Beijing Tsinghua Chang Gung Hospital
• Information provided by (Responsible Party): Beijing Tsinghua Chang Gung Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hepatocellular Carcinoma	Procedure: DEB-TACE; Procedure: cTACE; Device: Drug-eluting Beads; Drug: Epirubicin	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 226 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of TACE on Downstaging Hepatocellular Carcinoma Beyond UCSF Criteria: a Multi-center, Randomized, Parallel-controlled Study
• Actual Study Start Date: March 18, 2020
• Estimated Primary Completion Date: November 2022
• Estimated Study Completion Date: December 2025

Arms and Interventions

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)	Procedure: cTACE; Transcatheter arterial chemoembolization; Drug: Epirubicin; Chemotherapy drug for intra-arterial infusion

Outcome Measures

Primary Outcome Measures :

1. Downstaging success rate [ Time Frame: Within 6 months after surgery ]
   Criteria for success rate in downstaging meet UCSF criteria or the standard for liver resection.

Secondary Outcome Measures :

1. Complete response (CR) [ Time Frame: 1, 3, 6 months after surgery ]
   Disappearance of any intratumoral arterial enhancement in all target lesions
2. Partial response (PR) [ Time Frame: 1, 3, 6 months after surgery ]
   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
3. Stable disease (SD) [ Time Frame: up to 6months after TACE procedure ]
   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
4. Progressive disease (PD) [ Time Frame: 1, 3, 6 months after surgery ]
   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
5. Objective response (OR) [ Time Frame: 1, 3, 6 months after surgery ]
   CR+PR
6. Duration of downstaging [ Time Frame: within 36 months ]
   Interval between initial TACE treatment and the success or failure of downstaging according to the UCSF criteria assessed by the dynamic enhanced CT ;
7. Times of TACE treatments [ Time Frame: within 36 months ]
   Times of TACE surgery
8. Changes of tumor biomarkers (AFP, PIVKA-Ⅱ) [ Time Frame: From 7 days before TACE or curative treatments to the endpoints of the trial.(Up to 36 months) ]
   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
9. Changes in liver function [ Time Frame: from the date of the first TACE to the end of the clinical trial or the death of the patient，Up to 36months ]
   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)
10. Tumor-free survival (TFS) [ Time Frame: Within 36 months ]
    as the time from surgery initiation to tumor recurrence or death from any cause
11. Progression-free survival (PFS) [ Time Frame: Within 36 months ]
    as the time from surgery initiation to disease progression or death from any cause
12. Overall survival (OS) [ Time Frame: Within 36 months ]
    as the time from surgery initiation to death from any cause
13. Recurrence rate of Hepatocellular carcinoma [ Time Frame: Within 36 months ]
    Recurrence rate of hepatocellular carcinoma

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Jiahong Dong, MD; 01056118763; dongjiahong@mail.tsir

Locations

China

Beijing Tsinghua Chang Gung Hospital; Recruiting

Beijing, China

Contact: Jiahong Dong 13240009509

Sponsors and Collaborators

Beijing Tsinghua Chang Gung Hospital

More Information

• Responsible Party: Beijing Tsinghua Chang Gung Hospital
• ClinicalTrials.gov Identifier: NCT04738188
• Other Study ID Numbers: 19229-0-02
• First Posted: February 4, 2021
• Last Update Posted: February 4, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Beijing Tsinghua Chang Gung Hospital:

Hepatocellular Carcinoma

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Hepatocellular; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Epirubicin; Antibiotics, Antineoplastic; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action