Chemotherapy or Not, Following Complete Treatment of Hepatic Cancer in Cirrhotic Patients (GEMOXIAL)

May 4, 2011 updated by: Assistance Publique - Hôpitaux de Paris

Arterial LIPIODOLISED Chemotherapy Versus Systemic Chemotherapy With Gemcitabine Plus Oxaliplatin (GEMOX) Versus no Treatment Following Surgical Resection or Local Ablation of Hepatocellular Carcinoma in Cirrhotic Patients

Besides liver transplantation, the curative treatment of primary hepatic cancer with cirrhosis remains the surgical resection. Radiofrequency or cryotherapy currently allow local ablation of small cancer, with very good results. However, all these treatments are followed by high rates of recurrence (50 - 70% at 5 years). Then, it seems essential to associate to the surgical resection or to the local ablation as "adjuvant" treatment, in order to prevent or to decrease the rate of recurrence. However, no evidence supports this attitude. Therefore, following curative treatment of primary hepatic cancer with cirrhosis, we propose to compare treated to untreated patients. Postoperative treatment means either intra-arterial chemotherapy or systemic chemotherapy. The main criterion of the study is time of survival without recurrence. The main secondary objective is the safety.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The best treatment for hepatocellular carcinoma (HCC) with cirrhosis, currently is liver transplantation because treating the cancer and the causal disease. For the majority of patients, transplantation is not proposed, and the curative treatment remains the surgical resection. Radiofrequency or cryotherapy currently allows local destruction (or ablation) of the small HCC, with results that seem equivalent to the surgical resection. These last techniques increase the therapeutic possibilities in the presence of hepatic insufficiency. However, all these treatments are followed by high rates of recurrence (50 - 70% at 5 years and close to 100% at 10 years). The development of tumoral nodules, undetected at the time of the curative treatment, or the occurrence of new HCC, under the effects of the cirrhotic process or viral genomic modifications explain these disappointing results. Therefore, it seems essential to associate an adjuvant treatment to the surgical resection or the local destruction. Intra-arterial chemotherapy with or without embolisation is a largely evaluated therapeutic approach whose results are contradictory. Several retrospective studies, seem nevertheless to show a benefit of this treatment in adjuvant situation. Systemic chemotherapy for a long time regarded as ineffective, currently has a renewed interest due to the use of new drugs like gemcitabine and oxaliplatin (GEMOX regimen). This regimen showed a certain effect in a phase II study in advanced forms of HCC with cirrhosis. We propose to test by a prospective randomized multicentric phase III study, the effectiveness of an adjuvant treatment by systemic chemotherapy or intra-arterial LIPIODOLISED chemotherapy (CIAL), after surgery or complete local destruction of HCC. Three groups will be compared: a group of untreated patients (n=109), a group of patients treated by intra-arterial chemotherapy (CIAL = cisplatin 75 mg + lipiodol 10 ml; 3 courses every 6 weeks)(n=77) and a group of patients treated by systemic chemotherapy (GEMOX= day 1: gemcitabine 1000 mg/m² iv within 100 min; day 2: oxaliplatin 100 mg/m² iv within 2h; 8 courses every 2 weeks, d1 = d14)(n=77). Selection and randomisation are planned 4-8 weeks following complete treatment of the HCC. Identical follow up for the 3 groups includes clinical, biological, morphological exams every 3 months for 2 years, then every 6 months for 3 years. The main criterion of the study is survival without recurrence. The secondary objectives are the global survival, the safety and an estimate of the costs of the various treatments. The awaited results are 1) to demonstrate the effectiveness of at least one of these adjuvant treatment following complete treatment of HCC in cirrhotic patients and 2) to determine the best adjuvant treatment. Estimated inclusion time is 2 years, with an analysis of the principal criterion at 3 years. Follow-up of 5 years is envisaged for each patient, leading to a 7 years duration study.

Study Type

Interventional

Enrollment (Actual)

263

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Poissy, France, 75013
        • Urc La Pitie Salpetriere,

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:

  • Hepatocellular carcinoma (histology or Barcelona criteria) curatively treated by surgical resection or by radiofrequency or by cryotherapy
  • Evidence of liver cirrhosis (clinical, biological, endoscopic or histological criteria)
  • Morphological evaluation 4 to 6 weeks following curative treatment
  • No evidence of local or distant disease on the morphological evaluation
  • Absence of peritoneal or lymph node metastasis
  • Absence of pre- or per-operative macroscopic tumoral thrombus
  • Minimal free margin of 5 mm following pathological exam
  • ALPHAAFOETOPROTEINE level of less than 4 normal values or decreased by 50%, 4 to 6 weeks following curative treatment

  • Biological criteria, 2 weeks before treatment as follow:

    • neutrophilic polymorphonuclear > 1500/mm3,
    • platelets > 100 000/mm3,
    • total bilirubin < 25 mmol/l (1.46 mg/dl),
    • creatinin < 1.5 x normal value
  • Eastern Cooperative Oncology Group (ECOG) equal to 0 or 1
  • Life expectancy > 12 weeks
  • Absence of sensitive neuropathy at inclusion time
  • Health insurance coverage
  • Efficient contraceptive method if applicable
  • Signed informed consent

Exclusion Criteria:

  • Curative treatment performed 10 weeks or more before the beginning of adjuvant treatment
  • Contraindication to an angiography or hepatic artery thrombosis or portal thrombosis.
  • Pregnant or breastfeeding woman
  • Concomitant involvement to any clinical trial
  • Decompensate cirrhosis and Child-Pugh score ≥ 8 or clinical ascitis.
  • Cancer of the Liver Italian Program (C.L.I.P.) score ≥ 2
  • Heart or lung insufficiency
  • Other cancer not considered as definitively cured
  • Creatinin clearance < 30 ml/min
  • Recurrence of HCC less than 12 months following any last treatment
  • Any radiotherapy during the 4 weeks before inclusion
  • Known sensitivity to any drug of this protocol
  • Immunodeficiency (HIV+, transplanted patient)
  • Inability of follow up
  • Impossibility of clear understanding of the protocol for no french speaking patient
  • Patient under legal protection

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Oxaliplatin, gemcitabine, cisplatin, lipiodol
Drug: Oxaliplatin, gemcitabine, cisplatin, lipiodol
Oxaliplatin, gemcitabine, cisplatin, lipiodol
Experimental: 2
Oxaliplatin, gemcitabine, cisplatin, lipiodol
Drug: Oxaliplatin, gemcitabine, cisplatin, lipiodol
Oxaliplatin, gemcitabine, cisplatin, lipiodol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Survival without recurrence at 2 years
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Morbidity and mortality following adjuvant treatment
Time Frame: at 6 months
at 6 months

Collaborators and Investigators

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

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Eric Savier, MD, Assistance Publique - Hôpitaux de Paris

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

June 1, 2007

Primary Completion (Actual)

November 1, 2008

Study Completion (Actual)

November 1, 2008

Study Registration Dates

First Submitted

May 4, 2007

First Submitted That Met QC Criteria

May 4, 2007

First Posted (Estimate)

May 7, 2007

Study Record Updates

Last Update Posted (Estimate)

May 5, 2011

Last Update Submitted That Met QC Criteria

May 4, 2011

Last Verified

May 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P051062

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.

Clinical Trials on Liver Cirrhosis

Clinical Trials on Oxaliplatin, gemcitabine, cisplatin, lipiodol

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Netherlands

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe