Adjuvant Chemotherapy With FOLFOX in HCC Patients After Resection

Carcinoma, Hepatocellular Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02738697
• Other study ID #: SYSUCC-HCC-ADCHEMO
• Status: Recruiting
• Phase: Phase 3
• First received: March 24, 2016
• Last updated: November 1, 2016
• Start date: January 2016
• Est. completion date: December 2021

Study information

• Verified date: November 2016
• Source: Sun Yat-sen University
• Contact: Rong-Ping Guo, M.D.
• Phone: 00862087342266
• Email: guorp[@]sysucc.org.cn
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 290
• Est. completion date: December 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 3~5 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 FOLFOX 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular

Intervention

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

Procedure:
• Follow-up
Patients received just follow-up instead of adjuvant chemotherapy

Locations

Country	Name	City	State
China	SUN YAT-SEN University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (5)

Bruix J, Takayama T, Mazzaferro V, Chau GY, Yang J, Kudo M, Cai J, Poon RT, Han KH, Tak WY, Lee HC, Song T, Roayaie S, Bolondi L, Lee KS, Makuuchi M, Souza F, Berre MA, Meinhardt G, Llovet JM; STORM investigators.. Adjuvant sorafenib for hepatocellular ca — View Citation

Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, Sherman M, Schwartz M, Lotze M, Talwalkar J, Gores GJ; Panel of Experts in HCC-Design Clinical Trials.. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer — View Citation

Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, B — View Citation

Qin S, Bai Y, Lim HY, Thongprasert S, Chao Y, Fan J, Yang TS, Bhudhisawasdi V, Kang WK, Zhou Y, Lee JH, Sun Y. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients — View Citation

Qin S, Cheng Y, Liang J, Shen L, Bai Y, Li J, Fan J, Liang L, Zhang Y, Wu G, Rau KM, Yang TS, Jian Z, Liang H, Sun Y. Efficacy and safety of the FOLFOX4 regimen versus doxorubicin in Chinese patients with advanced hepatocellular carcinoma: a subgroup anal — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	The overall survival is defined as the percentage of patients who are alive at 5 years after their enrollments of this study.	5 years	No
Secondary	Disease-free survival	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.	5 years	No
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	5 years	Yes