Clinical trial NCT02788526: Adjuvant TACE to Reduce the HCC Recurrence After Resection
Official title: The Clinical Randomized Trial of Adjuvant Transarterial Chemo Embolization (TACE) to Reduce the Recurrence in Hepatocellular Carcinoma (HCC) Patients at High Risk After Resection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Hepatocellular
Keywords: Carcinoma,Hepatocellular
Chemoembolization
Adjuvant therapy
Hepatocellular
Microvessels invasion
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2016-06-02
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Hepatocellular carcinoma (HCC) is the sixth most common malignancies worldwide and the second leading cause of cancer-related death. Surgical resection is still the main radical approach for HCC, but the recurrence rate after hepatectomy is very high, which hampers the further improvement of prognosis of HCC patients. The conventional risk factors of recurrence including: huge tumor, multiple lesions, vessels invasion and tumor rupture. Recently, the microvessels invasion (MVI) has been recognized a novel risk factor of recurrence after hepatectomy. The investigators' previous study showed that the recurrence rate is more than 50% for the patients with \>5cm solitary tumor and MVI. The MVI was confirmed as the only independent risk factor for the overall and disease-free survival of HCC patients in multiple variables analysis. It is important to reduce the recurrence and prolong the survival of patients after hepatectomy with effective adjuvant therapy. TACE has been utilized as an adjuvant therapy after hepatectomy, but its significance is still unknown. Then, the investigators design the current prospective randomized clinical trial to evaluate the effect of adjuvant TACE to reduce the recurrence in HCC patients at high risk (\>5cm solitary tumor and MVI) after resection, compared to vigilant follow-up.

Detailed description: The patients with solitary tumor more than 5cm and microvessels invasion after radical hepatectomy were randomized to receive adjuvant TACE（1\~2 cycles, 4\~6 weeks) or follow-up. The main endpoint: overall survival (OS), disease-free survival(DFS), and safety were compared between this two groups.

Eligibility criteria: Inclusion Criteria:

1. Age 18\~75 years;
2. Eastern Cooperative Oncology Group performance status (ECOG PS) score \<=2;
3. Histologically confirmed hepatocellular carcinoma with microvessels invasion;
4. No previous treatment for HCC;
5. More than 5 cm solitary tumor before surgery confirmed by more than 2 radiological examinations;
6. R0 resection achieved;
7. No recurrence evidence in radiological follow-up 3\~7 weeks after surgery;
8. Adequate hematologic parameters and liver and kidney functions: (1) Neutrophils Absolute \>=1.5\*10\^9/L; (2) Hemoglobin \>=90g/L; (3) Platelet count \>=75\*10\^9/L; (4) Serum albumin \>=35g/L; (5) Serum total bilirubin \<=1.5\* upper limit of normal (ULN); (6) Serum Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) \<2.5\*ULN; (7) Serum creatinine \<=1.5\*ULN; (8) International normalized ratio (INR) \<=1.5;
9. Give signed informed consent before enrollment.

Exclusion Criteria:

1. Function impairment of vital organs (heart, lung, kidney, etc), serious infection or \>grade 2 adverse events (Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0);
2. Histologically confirmed of positive resection margin (R1 resection);
3. Previous or current malignant tumor beyond HCC;
4. Allergy to any agent of the TACE regimen;
5. History of organ transplantation;
6. Previously receiving other treatments for HCC;
7. Pregnant or breastfeeding women, and women of childbearing potential without adequate contraception;
8. Neurological or mental abnormalities that may affect cognitive assessment and inform consent;
9. Concomitant anti-tumor therapy or participating in other interventional clinical trials;
10. Other psychological, family or social reason, which would affect compliance with the study protocol.

Primary outcomes:
measure: Overall survival
timeFrame: 5 years
Secondary outcomes:
measure: Disease-free survival
timeFrame: 5 years
measure: Safety: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 5 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: SUN YAT-SEN University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Rong-ping GUO, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhong C, Guo RP, Li JQ, Shi M, Wei W, Chen MS, Zhang YQ. A randomized controlled trial of hepatectomy with adjuvant transcatheter arterial chemoembolization versus hepatectomy alone for Stage III A hepatocellular carcinoma. J Cancer Res Clin Oncol. 2009 Oct;135(10):1437-45. doi: 10.1007/s00432-009-0588-2. Epub 2009 May 1.
citation: Li JQ, Zhang YQ, Zhang WZ. [Evaluation of chemoembolization as an adjuvant therapy for primary liver carcinoma after surgical resection]. Zhonghua Zhong Liu Za Zhi. 1994 Sep;16(5):387-9. Chinese.
citation: Li JQ, Zhang YQ, Zhang WZ, Yuan YF, Li GH. Randomized study of chemoembolization as an adjuvant therapy for primary liver carcinoma after hepatectomy. J Cancer Res Clin Oncol. 1995;121(6):364-6. doi: 10.1007/BF01225689.
citation: Peng B, Liang L, He Q, Zhou F, Luo S. Surgical treatment for hepatocellular carcinoma with portal vein tumor thrombus. Hepatogastroenterology. 2006 May-Jun;53(69):415-9.