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

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04738188
• Other study ID #: 19229-0-02
• Status: Recruiting
• Phase: N/A
• Start date: March 18, 2020
• Est. completion date: December 2025

Study information

• Verified date: February 2021
• Source: Beijing Tsinghua Chang Gung Hospital
• Contact: Jiahong Dong, MD
• Phone: 01056118763
• Email: dongjiahong[@]mail.tsir
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 226
• Est. completion date: December 2025
• Est. primary completion date: November 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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 ?; according to New York Heart Association (NYHA) standard, patients with heart failure in stage ?~?; 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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Procedure:
• DEB-TACE
Drug-eluting beads transcatheter arterial chemoembolization
• cTACE
Transcatheter arterial chemoembolization

Device:
• Drug-eluting Beads
Drug-eluting beads

Drug:
• Epirubicin
Chemotherapy drug for intra-arterial infusion

Locations

Country	Name	City	State
China	Beijing Tsinghua Chang Gung Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Tsinghua Chang Gung Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Downstaging success rate	Criteria for success rate in downstaging meet UCSF criteria or the standard for liver resection.	Within 6 months after surgery
Secondary	Complete response (CR)	Disappearance of any intratumoral arterial enhancement in all target lesions	1, 3, 6 months after surgery
Secondary	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
Secondary	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
Secondary	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
Secondary	Objective response (OR)	CR+PR	1, 3, 6 months after surgery
Secondary	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
Secondary	Times of TACE treatments	Times of TACE surgery	within 36 months
Secondary	Changes of tumor biomarkers (AFP, PIVKA-?)	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)
Secondary	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
Secondary	Tumor-free survival (TFS)	as the time from surgery initiation to tumor recurrence or death from any cause	Within 36 months
Secondary	Progression-free survival (PFS)	as the time from surgery initiation to disease progression or death from any cause	Within 36 months
Secondary	Overall survival (OS)	as the time from surgery initiation to death from any cause	Within 36 months
Secondary	Recurrence rate of Hepatocellular carcinoma	Recurrence rate of hepatocellular carcinoma	Within 36 months