Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT02109146 |
Other study ID # |
2014-103 |
Secondary ID |
|
Status |
Completed |
Phase |
Phase 3
|
First received |
|
Last updated |
|
Start date |
October 23, 2013 |
Est. completion date |
May 13, 2023 |
Study information
Verified date |
May 2024 |
Source |
Zhejiang University |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
1. Hepatocellular carcinoma (HCC) is the most common primary malignancy of liver,
representing the third leading cause of cancer-related death worldwide.
2. Its overall dismal prognosis is a result of high incidence rates of metastasis and
postoperative recurrence, in particular the intrahepatic recurrence.
3. TACE is the most widely used primary treatment for unresectable HCC. It was also used as
the optional treatment for relapsed disease. However, the efficacy of TACE used as
adjuvant therapy following hepatectomy remains controversial.
Description:
This multicenter, phase 3, randomized, open-label trial was done at two centers: The First
Affiliated Hospital of Zhejiang University School of Medicine (FAHZU), Hangzhou, China; and
the Second Affiliated Hospital of Zhejiang University School of Medicine (SAHZU), Hangzhou,
China. Eligible patients were between 18 and 75 years of age with histologically proven T1 or
T2 HCC (according to the AJCC TNM Classification of HCC, 7th); an Eastern Cooperative
Oncology Group (ECOG) performance status of 0 or 1; Child-Pugh class A or B; no history of
neoadjuvant therapy; no lymph node or distant metastasis; no intrahepatic or extrahepatic
recurrence at radiological follow-up (4-6 weeks after surgery); adequate bone marrow,
hepatic, and renal function according to laboratory test results. Patients were excluded if
they had undergone margin-positive resections or resection of recurrence HCC; had lymph node
or distal metastases; underwent concomitant ablation or radiation during surgery; were
subjected to severe postoperative complications; had serious co-morbidities; had known
allergy to iodine and drugs used in TACE; or if an investigator judged participation to be
incompatible with the safety of the study. This clinical trial was done in accordance with
the Declaration of Helsinki and local laws. All participants provided written informed
consent. The study protocol was approved by the institutional Medical Ethics Review
Committee.
Participants enrolled in the adjuvant TACE group received one to two cycles of TACE with an
interval of 4~6 weeks, and the first TACE was given within 1 week after randomization.
Participants enrolled in the observation group were subjected to active surveillance without
any adjuvant treatment. The TACE procedure was performed as follows. Briefly, a 4F or 5F
catheter was introduced into the abdominal aorta through the superficial femoral artery
according to the Seldinger technique. Angiography of the celiac and superior mesenteric
arteries was performed to show the hepatic arterial supply. Then the left and right hepatic
arteries were accessed by a microcatheter and intraarterial epirubicin (40 mg) and
oxaliplatin (150 mg) in a mixture of lipiodol (3~5 mL) were injected. The follow-up interval
was 3 months in the first two years postoperatively and 6 months thereafter. During each
follow-up visit, blood tests including complete blood count, serum level of alpha-fetoprotein
(AFP), and liver function tests were examined. During follow-up, contrast-enhanced abdominal
CT or MRI scans were first performed at 3 months after operation and then every 6 months,
with liver ultrasonography performed 3 months after every CT/MRI scan thereafter. Chest CT
was performed at 1-year intervals. All participants with tumor recurrence were treated
according to the decision made by a multidisciplinary board.
The primary endpoint was RFS, defined as the time from randomization to the first documented
HCC recurrence by independent radiological assessment or death due to any cause, whichever
occurred first. Secondary endpoints were OS (defined as the time from randomization to death
due to any cause), RFS rate, and safety. Patients who were recurrence-free or alive at the
point of final analysis were censored at the date of the last follow-up.
Intrahepatic recurrence was defined according to the non-invasive criteria of the European
Association for the Study of the Liver (EASL) guideline. Newly-onset intrahepatic nodules
with the longest diameter ≥ 1cm and a typical hallmark of HCC on contrast-enhanced CT/MRI
imaging (hypervascular in the arterial phase with washout in the portal venous or delayed
phase) were diagnosed as HCC recurrence. Lesions ≥ 1cm without a typical vascular pattern
could also be diagnosed as HCC recurrence by evidence of a fast growth pattern as showed in
subsequent scans and were independently reviewed by two radiologists. Extrahepatic recurrence
was defined as per Response Evaluation Criteria in Solid Tumors. The safety of adjuvant TACE
was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version
4.03.