Chemotherapy or Not, Following Complete Treatment of Hepatic Cancer in Cirrhotic Patients (GEMOXIAL)
Primary Purpose
Liver Neoplasms, Liver Cirrhosis, Carcinoma, Hepatocellular
Status
Terminated
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Oxaliplatin, gemcitabine, cisplatin, lipiodol
Sponsored by
About this trial
This is an interventional prevention trial for Liver Neoplasms focused on measuring Recurrence, Neoplasm Recurrence, Local, Liver, Liver Neoplasms, Liver Cirrhosis, Carcinoma, Hepatocellular, Iodized Oil, gemcitabine [Substance Name], oxaliplatin [Substance Name], gemcitabine-oxaliplatin regimen [Substance Name], Randomized Controlled Trials, Multicenter Studies, Cisplatin, Injections, Intra-Arterial, Injections, Intravenous, Chemotherapy, Adjuvant
Eligibility Criteria
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
Sites / Locations
- Urc La Pitie Salpetriere,
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
1
2
Arm Description
Oxaliplatin, gemcitabine, cisplatin, lipiodol
Oxaliplatin, gemcitabine, cisplatin, lipiodol
Outcomes
Primary Outcome Measures
Survival without recurrence at 2 years
Secondary Outcome Measures
Morbidity and mortality following adjuvant treatment
Full Information
NCT ID
NCT00470340
First Posted
May 4, 2007
Last Updated
May 4, 2011
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT00470340
Brief Title
Chemotherapy or Not, Following Complete Treatment of Hepatic Cancer in Cirrhotic Patients
Acronym
GEMOXIAL
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2007
Overall Recruitment Status
Terminated
Why Stopped
during the study
Study Start Date
June 2007 (undefined)
Primary Completion Date
November 2008 (Actual)
Study Completion Date
November 2008 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Neoplasms, Liver Cirrhosis, Carcinoma, Hepatocellular, Recurrence, Neoplasm Recurrence, Local
Keywords
Recurrence, Neoplasm Recurrence, Local, Liver, Liver Neoplasms, Liver Cirrhosis, Carcinoma, Hepatocellular, Iodized Oil, gemcitabine [Substance Name], oxaliplatin [Substance Name], gemcitabine-oxaliplatin regimen [Substance Name], Randomized Controlled Trials, Multicenter Studies, Cisplatin, Injections, Intra-Arterial, Injections, Intravenous, Chemotherapy, Adjuvant
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
263 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Oxaliplatin, gemcitabine, cisplatin, lipiodol
Arm Title
2
Arm Type
Experimental
Arm Description
Oxaliplatin, gemcitabine, cisplatin, lipiodol
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin, gemcitabine, cisplatin, lipiodol
Intervention Description
Oxaliplatin, gemcitabine, cisplatin, lipiodol
Primary Outcome Measure Information:
Title
Survival without recurrence at 2 years
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Morbidity and mortality following adjuvant treatment
Time Frame
at 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Savier, MD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Urc La Pitie Salpetriere,
City
Poissy
ZIP/Postal Code
75013
Country
France
12. IPD Sharing Statement
Learn more about this trial
Chemotherapy or Not, Following Complete Treatment of Hepatic Cancer in Cirrhotic Patients
We'll reach out to this number within 24 hrs