Adjuvant Chemotherapy With FOLFOX in HCC Patients After Resection

Sponsor

Sun Yat-sen University (Other)

Overall Status

Unknown status

CT.gov ID

NCT02738697

Collaborator

(none)

290

Enrollment

Location

Arms

Duration (Months)

4.1

Patients Per Site Per Month

Study Details

Study Description

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. Reported at 2014 American Society of Clinical Oncology (ASCO) annual meeting, A phase III randomized, double-blind, placebo-controlled trial of adjuvant sorafenib after resection or ablation to prevent recurrence of hepatocellular carcinoma (STORM trial) failed to meet the primary endpoint-recurrence free survival (RFS). Given the inspiring result of a recent trial, which compared with single agent of doxorubicin, the oxaliplatin-containing regimens (FOLFOX) showed significant improvement in OS, objective response rate (ORR) and disease control rate (DCR) in Asian (especially China) HCC patients. Based on these rationales, the investigators design the current prospective randomized clinical trial to evaluate the effect of adjuvant chemotherapy with FOLFOX to prolong the overall survival and reduce the recurrence in HCC patients at high risk (>5cm solitary tumor and MVI) after resection, compared to vigilant follow-up.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Hepatocellular	Drug: Adjuvant chemotherapy Procedure: Follow-up	Phase 3

Detailed Description

The patients with solitary tumor more than 5cm and microvessels invasion after radical hepatectomy were randomized to receive adjuvant FOLFOX chemotherapy （8~12 cycles) or follow-up. The main endpoint: overall survival (OS), disease-free survival(DFS) and safety were compared between this two groups.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

290 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Clinical Randomized Trial of Adjuvant Chemotherapy With FOLFOX in HCC Patients at High Risk After Resection

Study Start Date :

Jan 1, 2016

Anticipated Primary Completion Date :

Dec 1, 2020

Anticipated Study Completion Date :

Dec 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Adjuvant chemotherapy 8~12 cycles of adjuvant chemotherapy with FOLFOX were performed 4-6 weeks after radical surgery	Drug: Adjuvant chemotherapy 8~12 cycles of adjuvant chemotherapy with FOLFOX were performed 4-6 weeks after radical surgery Other Names: adjuvant chemotherapy with FOLFOX
Other: Follow-up Routine follow-up were performed instead of adjuvant chemotherapy	Procedure: Follow-up Patients received just follow-up instead of adjuvant chemotherapy

Arm

Intervention/Treatment

Experimental: Adjuvant chemotherapy

8~12 cycles of adjuvant chemotherapy with FOLFOX were performed 4-6 weeks after radical surgery

Drug: Adjuvant chemotherapy

8~12 cycles of adjuvant chemotherapy with FOLFOX were performed 4-6 weeks after radical surgery

Other Names:

adjuvant chemotherapy with FOLFOX

Other: Follow-up

Routine follow-up were performed instead of adjuvant chemotherapy

Procedure: Follow-up

Patients received just follow-up instead of adjuvant chemotherapy

Outcome Measures

Primary Outcome Measures

Overall survival [5 years]
The overall survival is defined as the percentage of patients who are alive at 5 years after their enrollments of this study.

Secondary Outcome Measures

Disease-free survival [5 years]
The disease-free survival is defined as the percentage of patients who are alive at 5 years without any signs or symptoms of HCC after their enrollments of this study.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [5 years]
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18~75 years;
Eastern Cooperative Oncology Group performance status (ECOG PS) score <=2;
Histologically confirmed hepatocellular carcinoma with microvessels invasion;
No previous treatment for HCC;
More than 5 cm solitary tumor before surgery confirmed by more than 2 radiological examinations;
R0 resection achieved;
No recurrence evidence in radiological follow-up 3~5 weeks after surgery;
Adequate hematologic parameters and liver and kidney functions: (1) Neutrophils Absolute >=1.510^9/L; (2) Hemoglobin >=90g/L; (3) Platelet count >=7510^9/L; (4) Serum albumin >=35g/L; (5) Serum total bilirubin <=1.5upper limit of normal (ULN); (6) Serum Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) <2.5ULN; (7) Serum creatinine <=1.5*ULN; (8) International normalized ratio (INR)<=1.5;
Give signed informed consent before enrollment.

Exclusion Criteria:

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);

Histologically confirmed of positive resection margin (R1 resection);
Previous or current malignant tumor beyond HCC;
Allergy to any agent of the FOLFOX regimen;
History of organ transplantation;
Previously receiving other treatments for HCC;
Pregnant or breastfeeding women, and women of childbearing potential without adequate contraception;
Neurological or mental abnormalities that may affect cognitive assessment and inform consent;
Concomitant anti-tumor therapy or participating in other interventional clinical trials;
Other psychological, family or social reason, which would affect compliance with the study protocol.