Hepatocellular Carcinoma
Conditions
Keywords
Hepatocellular Carcinoma, Drug-eluting bead transarterial chemoembolization, Conventional transarterial chemoembolization, Objective response
Brief summary
this multi-center prospective cohort study is to evaluate the efficacy and the safety of drug-eluting bead TACE compared with conventional TACE in terms of objective response in unresectable HCC
Interventions
PROCEDUREDEB-TACE
Patients in the DEB-TACE group received a maximum dose of 4 ml of DC bead (diameter 75-500 um) loaded with a maximum dose of 150 mg of anthracyclines drugs, such as doxorubicin. The anticancer agents and the diameter of DC Bead for individual patient will be selected according to the common clinical practice of each center. Treatment endpoint consisted of stasis of flow within feeding vessel(s) or completed delivery of maximum single-session dose of 150 mg doxorubicin. TACE will be repeated on demand according to the radiological response.
PROCEDUREcTACE
Patients in the cTACE group were treated with anthracyclines, such as doxorubicin, in a mixture of lipiodol. Administration of the anticancer in oil emulsion was followed by injection of embolic materials such as gelfoam or PVA particles until complete stasis in segmental or subsegmental arterial branches. the tumor-feeding vessels should be superselected whenever possible. The anticancer agents for individual patient will be selected according to the common clinical practice of each center. TACE will be repeated on demand according to the radiological response.
Sponsors
Air Force Military Medical University, China
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Prior informed consent 2. Confirmed Diagnosis of HCC: a. Cirrhotic subjects: Clinical diagnosis by American Association for the Study of Liver Diseases (AASLD) criteria. HCC can be defined in cirrhotic subjects by one imaging technique (CT scan, MRI, or second generation contrast ultrasound) showing a nodule larger than 2 cm with contrast uptake in the arterial phase and washout in venous or late phases or two imaging techniques showing this radiological behavior for nodules of 1-2 cm in diameter. Cytohistological confirmation is required for subjects who do not fulfill these eligibility criteria. b. Non-cirrhotic subjects: For subjects without cirrhosis, histological or cytological confirmation is mandatory. Documentation of original biopsy for diagnosis is acceptable 3. Patients with unresectable Barcelona Clinic Liver Cancer (BCLC) stage A and BCLC B, and all patients have a intermediate or high tumor burden (the diameter of largest tumor plus tumor number is more than 6) 4. Child Pugh class A/B(7) class without decompensated liver cirrhosis. 5. ECOG Performance Status 0 score 6. At least one uni-dimensional lesion measurable by MRI or CT according to the RECIST 1.1 criteria 7. Male or female subject larger than 18 years of age 8. Life expectance of at least 12 weeks. 9. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 4 weeks after the completion of trial 10. Adequate bone marrow, liver and renal function as assessed by central lab by means of the following laboratory requirements from samples within 7 days prior to randomization: 1. Hemoglobin \> 9.0 g/dl 2. Absolute neutrophil count (ANC) \>1,500/mm3 3. Platelet count≥50x109/L 4. ALB≥28g/L 5. Total bilirubin \< 2 mg/dL 6. Alanine aminotransferase(ALT) and aspartate aminotransferase(AST) \< 5 x upper limit of normal 7. Blood urea nitrogen(BUN) and creatinine \< 1.5 x upper limit of normal 8. International normalized ratio(INR) \< 1.7, or prothrombin time（PT） \< 4 seconds above control
Exclusion criteria
1. Portal vein or any vascular invasion 2. Presence of extra hepatic spread 3. Presence of metastasis in biliary tract or obstruction of biliary tract 4. Presence of metastasis in brain or presence of symptom of the brain metastasis but lack of further examination to exclude brain metastasis 5. Poor blood supply for the liver tumor lesions; poor blood supply refers that the tumor lesions fail to show obvious contrast uptake in the arterial phase and washout in venous or late phases by CT scan or MRI 6. Any contraindications for hepatic embolization procedures: 1. Known hepatofugal blood flow 2. Known porto-systemic shunt 3. Renal failure / insufficiency requiring hemo-or peritoneal dialysis 7. History of cardiac disease: 1. Congestive heart failure \>New York Heart Association (NYHA) class 2 2. Uncontrolled hypertension 8. Known history of HIV infection 9. Patients who have previously been receiving any treatments against HCC 10. Active clinically serious infections (\> grade 2 NCI-CTCAE Version 4.0), except for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection 11. Contraindication of Anthracyclines administration, such as Doxorubicin 12. Concurrent with other cancer 13. Pregnant or breast-feeding subjects 14. Women of childbearing age did not take any contraceptive measures 15. Clinically significant gastrointestinal bleeding within 12 weeks prior to start of study 16. Major surgery within 3 weeks prior to start of study drug (e.g. thoracolaparotomy is not allowed, but noninvasive surgery, e.g. biopsy, is allowed)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate | Tumor response will be assessed at week 4 and week 12 after initiation of treatment and thereafter every 8 weeks, up to 1 year | the percentage of patients who achieved complete response (CR) and partial response (PR) as the best response, according to the modified Response Evaluation Criteria In Solid Tumours (mRECIST) criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to progression | The last patient has been on study for 1year | Time to progression is measured from the treatment start to the radiologically confirmed progression |
| Adverse event | The adverse event will be assessed during in hospital and every 4 weeks, up to 1year | The terms and grade of adverse event will be present according to the Common Terminology Criteria for Adverse Event (CTCAE version 4.0) |
| Overall survival | The last patient has been on study for 1year | Overall survival (OS) is measured from the treatment start until all-cause death or the last follow-up date |
| Time to response | The last patient has been on study for 1year | Time to response (TTR) is measured from the treatment start to the firstly radiologically confirmed complete response or partial response. |
| Duration of response | The last patient has been on study for 1year | Duration of response (DOR) is measured from the first-time confirmed complete response or partial response to the date of radiological progression |
| Progression-free survival | The last patient has been on study for 1year | Progression-free survival (PFS) is measured from the treatment start until all-cause death or untreatable progression (vascular invasion, extra hepatic spread, the Eastern Cooperative Oncology Group (ECOG) performance status \>2, and Child-Pugh grade over C, but except hepatic new nodule) |
Countries
China
Contacts
Primary ContactGuohong Han, MD PHD
Backup ContactDongdong Xia, MD
Outcome results
None listed