NCT02738697

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
290

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Jan 2016

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2016

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

March 24, 2016

Completed
21 days until next milestone

First Posted

Study publicly available on registry

April 14, 2016

Completed
4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2020

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2021

Completed
Last Updated

November 2, 2016

Status Verified

November 1, 2016

Enrollment Period

4.9 years

First QC Date

March 24, 2016

Last Update Submit

November 1, 2016

Conditions

Carcinoma, Hepatocellular

Keywords

Carcinoma,HepatocellularAdjuvant chemotherapyMicrovessels invasionSurvivalRecurrence

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (2)

  • Disease-free survival

    5 years

  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    5 years

Study Arms (2)

Adjuvant chemotherapy

EXPERIMENTAL

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

Drug: Adjuvant chemotherapy

Follow-up

OTHER

Routine follow-up were performed instead of adjuvant chemotherapy

Procedure: Follow-up

Interventions

Adjuvant chemotherapyDRUG

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

Also known as: adjuvant chemotherapy with FOLFOX
Adjuvant chemotherapy
Follow-upPROCEDURE

Patients received just follow-up instead of adjuvant chemotherapy

Follow-up

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 \>=1.5\*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;
  • Give signed informed consent before enrollment.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

SUN YAT-SEN University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (5)

  • 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.

    PMID: 25223462RESULT

  • 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.

    PMID: 23980077RESULT

  • 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.

    PMID: 18650514RESULT

  • 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.

    PMID: 18477802RESULT

  • 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.

    PMID: 26361969RESULT

MeSH Terms

Conditions

Carcinoma, HepatocellularRecurrence

Interventions

Chemotherapy, AdjuvantFolfox protocol

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Combined Modality TherapyTherapeuticsDrug Therapy

Study Officials

  • Rong-Ping Guo, M.D.

    Sun Yat-sen University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Rong-Ping Guo, M.D.

CONTACT

00862087342266guorp@sysucc.org.cn

Wei Wei, Ph.D. M.D.

CONTACT

00862087343790weiwei@sysucc.org.cn

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

March 24, 2016

First Posted

April 14, 2016

Study Start

January 1, 2016

Primary Completion

December 1, 2020

Study Completion

December 1, 2021

Last Updated

November 2, 2016

Record last verified: 2016-11

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)