Clinical trial NCT04738188: Efficacy and Safety of TACE on Downstaging Hepatocellular Carcinoma Beyond UCSF Criteria;
Official title: Efficacy and Safety of TACE on Downstaging Hepatocellular Carcinoma Beyond UCSF Criteria: a Multi-center, Randomized, Parallel-controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular Carcinoma
Lead sponsor: Beijing Tsinghua Chang Gung Hospital
Sponsor class: OTHER
First posted: 2021-02-04
Enrollment: 226
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Downstaging success rate
timeFrame: Within 6 months after surgery
Secondary outcomes:
measure: Complete response (CR)
timeFrame: 1, 3, 6 months after surgery
measure: Partial response (PR)
timeFrame: 1, 3, 6 months after surgery
measure: Stable disease (SD)
timeFrame: up to 6months after TACE procedure
measure: Progressive disease (PD)
timeFrame: 1, 3, 6 months after surgery
measure: Objective response (OR)
timeFrame: 1, 3, 6 months after surgery
measure: Duration of downstaging
timeFrame: within 36 months
measure: Times of TACE treatments
timeFrame: within 36 months
measure: Changes of tumor biomarkers (AFP, PIVKA-Ⅱ)
timeFrame: From 7 days before TACE or curative treatments to the endpoints of the trial.(Up to 36 months)
measure: Changes in liver function
timeFrame: from the date of the first TACE to the end of the clinical trial or the death of the patient，Up to 36months
measure: Tumor-free survival (TFS)
timeFrame: Within 36 months
measure: Progression-free survival (PFS)
timeFrame: Within 36 months
measure: Overall survival (OS)
timeFrame: Within 36 months
measure: Recurrence rate of Hepatocellular carcinoma
timeFrame: Within 36 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tsinghua Chang Gung Hospital
Study officials:
References: