HR Combined With FOLFOX4 for HCC With PVTT

May 20, 2015 updated by: Zhen-Wei Peng, Sun Yat-sen University

Hepatic Resection Combined With or Without Oxaliplatin+5-Fluorouracil/ Leucovorin(5-FU/LV)(FOLFOX4) for Resectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most frequent cause of cancer death worldwide. Hepatic resection (HR) is the conventional ''curative'' treatment for HCC. In both the European and the United States Proposed Guidelines for HCC, HR is recommended only for patients with preserved liver function and with early stage HCC. Unfortunately, because of tumor multifocality, portal vein invasion, and underlying advanced cirrhosis, only 10% to 30% of HCCs are amenable to such a ''curative'' treatment at the time of diagnosis. Transarterialchemoembolization (TACE) has become the most popular palliative treatment for patients with unresectable HCC, and it is no longer considered as a contraindication to HCC with portal vein tumor thrombus (PVTT). Unfortunately, the long-term outcomes are generally poor for HCC treated with TACE, especially for HCC with PVTT. To improve on the results of treatment of HCC with PVTT, attempts have been made to perform HR for these patients. HCC with PVTT remains a contraindication to liver transplantation because of the high rate of tumor recurrence, and because of the severe shortage of donor organs. HR remains the only therapeutic option that may still offer a chance of cure. With advances in surgical techniques, it has become feasible to remove all gross tumors, including PVTT, which has extended to the main portal vein, safely by surgery. More HCC with PVTT, which previously were considered as unresectable, have become resectable.Recent studies have even shown favorable long-term survival outcomes of HR in well-selected cases of HCC with PVTT. However, the recurrence rate after HR for PVTT is still high and the prognosis for patients with HCC with PVTT is very poor. Systemic chemotherapy is considered to be one of the main treatments for malignant tumors. HCC is known to be highly refractory to conventional systemic chemotherapy because of its heterogeneity and multiple etiologies. Before the advent of the molecular-targeted agent sorafenib, which has subsequently become the standard of care, no standard systemic drug or treatment regimen had shown an obvious survival benefit in HCC. Nowadays, there is no systemic chemotherapy regimen had been definitively recommended as the standard for treating HCC. Clinical activity of several regimens containing oxaliplatin (OXA) in advanced HCC had been demonstrated in phase II studies. In a phase II study of the FOLFOX4 (infusional fluorouracil [FU], leucovorin[LV], and OXA) regimen in Chinese patients with HCC, median overall survival (OS) was 12.4 months, mean time to progression was 2.0 months, and the response rate (RR) was 18.2%. The safety profile was acceptable. Recently, the results of a phase Ⅲ randomize study showed that FOLFOX4 served as palliative chemotherapy can induce higher overall survival, progression-free survival and response rate comparing to doxorubicin in patients with advanced hepatocellular carcinoma from Asia. The safety data was also acceptable.So the investigators' hypothesis is that post-surgery FOLFOX4 can reduce high recurrence rate after HR for HCC with PVTT. The aim of this open-label, single prospective study is to evaluate the efficacy and safety of HR combined with FOLFOX4 systemic chemotherapy for patients with HCC with PVTT.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

51

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age between 18 and 75 years;
  2. Presence of PVTT on imaging, except PVTT extending to involve the superior mesenteric vein
  3. ECOG status 0;
  4. Resectable disease( defined as the possibility of completely removing all gross tumors and retaining a sufficient liver remnant to sustain life)

Exclusion Criteria:

  1. the presence of extrahepatic spread on imaging;
  2. a Child-Pugh class C liver cirrhosis, or ICG-R15 >30%, or evidence of hepatic decompensation including ascites, esophageal, or gastric variceal bleeding or hepatic encephalopathy;
  3. an American Society of Anesthesiologists (ASA) score ≥3.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HR combined with FOLFOX4
  1. HR ;
  2. FOLFOX4 4 weeks after HR
Procedure: HR

HR:

HR was carried out under general anesthesia using a right subcostal incision with a midline extension. Intraoperative ultrasound was routinely performed. Pringle's maneuver was routinely used with a clamp/unclamp time of 10 minutes/5 minutes.Thrombectomy was performed according to the location and extent of PVTT. The en bloc technique was used for patients if the portal vein branch could be ligated with a sufficient safety margin between its root and the tip of the thrombus

Drug: FOLFOX4

FOLFOX4(Oxaliplatin + 5-Fluorouracil/Leucovorin):

4 weeks after HR; Drug: Oxaliplatin + 5- Fluorouracil/Leucovorin Day 1: Oxaliplatin 85mg/m² 2h IV infusion, leucovorin 200mg/m² 2h IV infusion, 5-fluorouracil 400mg/m² IV bolus, 5-fluorouracil 600mg/m2 22h IV infusion.

Day 2: Leucovorin 200mg/m² 2h IV infusion, 5-fluorouracil 400mg/m² IV bolus, 5-fluorouracil 600mg/m² 22h IV infusion. Repeated every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Recurrence rate
Time Frame: 2 years
2 years
Number of Complications reported using the National Cancer Institute Common Toxicity Criteria grading version 4.0
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 2 years
2 years
Recurrence-free survival
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Investigators

  • Study Chair: Ming Kuang, M.D.,Ph.D., Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2015

Primary Completion (Anticipated)

May 1, 2016

Study Completion (Anticipated)

May 1, 2018

Study Registration Dates

First Submitted

May 5, 2015

First Submitted That Met QC Criteria

May 20, 2015

First Posted (Estimate)

May 25, 2015

Study Record Updates

Last Update Posted (Estimate)

May 25, 2015

Last Update Submitted That Met QC Criteria

May 20, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HCC002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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