Hepatocellular Carcinoma on Cirrhosis With Child A/B7 and Hepatic Intra Arterial Injection of Idarubicin/Lipiodol Emulsion

Study Overview
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Brief Summary
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The investigators propose in this trial to test a hepatic chemotherapy, consisting of the hepatic intra-arterial injection Idarubicin, emulsified with Lipiodol, lipid vector, without embolization in the treatment of non-metastatic, unresectable hepatocellular carcinoma on cirrhosis with Child-Pugh A/B7.

Official Title
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Traitement Des Carcinomes hépatocellulaires Sur Cirrhose Child A/B7 Par Injection Intra-artérielle hépatique d'Une émulsion de Lipiodol et Idarubicine : Etude de Phase II, Monobras, Multicentrique.

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Drug: Idarubicin and Lipiodol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-proven HCC or according to EASL criteria Child-Pugh A or B7 Disease that is not suitable for resection, ablation or radiofrequency Performance Status ECOG 0 or 1 BCLC A/B or C if Performance Status ECOG = 1 Measurable lesions according to mRECIST criteria No previous treatment with chemotherapy, radiotherapy or transarterial embolization (with or without chemotherapy) or radioembolisation Age superior or equal to 18 years Platelets > 50,000/mm3, Polynuclear neutrophils > 1000/mm3, Creatininemia < 150umol/L, Bilirubinemia < 5 mg/dL Absence of heart failure (Ultrasound LVEF > 50%) Women of child-bearing age using an adequate method of contraception throughout treatment Men using an adequate method of contraception throughout the treatment and at least 3 months after the end of treatment Written informed consent National health insurance cover Exclusion Criteria: Advanced tumor disease (extrahepatic except pulmonary micronodules <7mm of tumoral portal vein thrombosis on positron emission tomography are not a contra-indication.) Large HCC with liver invasion >50% History of other cancer than HCC and excluding cancers known to have been cured for more than 5 years, or basocellular skin tumors or cervical cancer in situ treated with adequate and curative purpose Advanced liver disease (Child B8, B9 or C) Contra-indication for the MRI (Pacemaker or neurosensorial stimulator or implantable defibrillator, cochlear implant, ferromagnetic foreing body similar to the nervous structure) Contra-indication to the injection of the gadolinium-based contrast agents (history of hypersensibility to the gadolinium chelates, meglumine). Contra-indication to idarubicin (Hypersensibility to active substance or excipients, cardiopathy with myocardial insufficiency of less than 6 months, serious arrhythmias, serious renal or liver failure, yellow fever vaccine or any other live attenuated vaccine, persistente myelosuppression, previous treatments with idarubicin and/or other anthracyclines or anthracenediones at maximum cumulative doses, stomatitis) Contra-indication to Lipiodol (Hypersensibility, proven hyperthyroidism, tromatic injuries, bleeding or recent bleeding) Concomitant disease or uncontrolled severe clinical situation Uncontrolled severe infection Vascular anatomy makes it impossible to perform hepatic intra-arterial treatments Pregnancy (Beta HCG positive) or breastfeeding Patient who for psychological, social, family or geographical reasons cannot be followed regularly Vulnerable person Concomitant participation of the patient in another research involving the human person

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: The purpose of this study is to assess efficacy and tolerance of hepatic intra-arterial injection of an emulsion of Idarubicine and Lipiodol for treatment of non-metastatic, unresectable hepatocellular carcinoma on cirrhosis with Child-Pugh A/B7.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment arm<br>hepatic intra-arterial injection of an emulsion of Idarubicine and Lipiodol | Drug: Idarubicin and Lipiodol<br>* Hepatic intra-arterial chemotherapy consisting of the hepatic intra-arterial injection Idarubicin, emulsified with Lipiodol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants presenting a disease control at 4 months | The primary outcome is to evaluate the disease control rate (partial, complete or stable response) 4 months after the first cycle of chemo-lipiodol using mRECIST criteria. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of chemo-lipiodol defined by NCI-CTCAE version 4.03 | Safety defined by NCI-CTCAE version 4.03 published 14 june 2010 | 12 months | 
| Objective response rate of chemo-lipiodol | Objective response rate according to mRECIST at 6 months after the first cycle | 6 months | 
| best response at 6 months after the first cycle of chemo-lipiodol according to mRECIST | The best response according to mRECIST at 6 months after the first cycle of chemo-lipiodol | 6 months | 
| Overall survival | Overall survival at 12 months after the first cycle of chemo-lipiodol | 12 months | 
| Quality of life questionnaire (QLQ) QLQ-C30 | Quality of life questionnaire at 12 months after the first cycle of chemo-lipiodol (QLQ-C30). Subscale minimum score is egal to 1 (not at all) and maximum score is egal to 4 (very much). The maximal score correspond to a better quality of life. Subscales are summed to compute a total score. | 12 months |