Adjuvant Chemotherapy With FOLFOX in HCC Patients After Resection

NCT ID: NCT02738697

Last Updated: 2016-11-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 290 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2021-12-31

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.

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.

Conditions

Carcinoma, Hepatocellular

Keywords

Carcinoma,Hepatocellular; Adjuvant chemotherapy; Microvessels invasion; Survival; Recurrence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Adjuvant chemotherapy

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

Group Type: EXPERIMENTAL

Adjuvant chemotherapy

Intervention Type: DRUG

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

Follow-up

Routine follow-up were performed instead of adjuvant chemotherapy

Group Type: OTHER

Follow-up

Intervention Type: PROCEDURE

Patients received just follow-up instead of adjuvant chemotherapy

Interventions

Adjuvant chemotherapy

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

Intervention Type: DRUG

Follow-up

Patients received just follow-up instead of adjuvant chemotherapy

Intervention Type: PROCEDURE

Other Intervention Names

adjuvant chemotherapy with FOLFOX

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 3~5 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Rong-ping Guo

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rong-Ping Guo, M.D.

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

SUN YAT-SEN University Cancer Center

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Rong-Ping Guo, M.D.

Role: CONTACT

Phone: 00862087342266

Email: guorp@sysucc.org.cn

Wei Wei, Ph.D. M.D.

Role: CONTACT

Phone: 00862087343790

Email: weiwei@sysucc.org.cn

Facility Contacts

Rong-Ping Guo, M.D.

Role: primary

Wei Wei, Ph.D. M.D.

Role: backup

References

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 analysis of the EACH study. Oncologist. 2014 Nov;19(11):1169-78. doi: 10.1634/theoncologist.2014-0190. Epub 2014 Sep 15.

Reference Type: RESULT

PMID: 25223462 (View on PubMed)

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 with advanced hepatocellular carcinoma from Asia. J Clin Oncol. 2013 Oct 1;31(28):3501-8. doi: 10.1200/JCO.2012.44.5643. Epub 2013 Aug 26.

Reference Type: RESULT

PMID: 23980077 (View on PubMed)

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, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. doi: 10.1056/NEJMoa0708857.

Reference Type: RESULT

PMID: 18650514 (View on PubMed)

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 Inst. 2008 May 21;100(10):698-711. doi: 10.1093/jnci/djn134. Epub 2008 May 13.

Reference Type: RESULT

PMID: 18477802 (View on PubMed)

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 carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2015 Oct;16(13):1344-54. doi: 10.1016/S1470-2045(15)00198-9. Epub 2015 Sep 8.

Reference Type: RESULT

PMID: 26361969 (View on PubMed)

Other Identifiers

SYSUCC-HCC-ADCHEMO

Identifier Type: -

Identifier Source: org_study_id