Clinical trial NCT04178642: The Impact on Hepatic Recurrence After Adjuvant Chemotherapy With Intraarterial Infusion of Idarubicin-Lipiodol
Official title: Hepatocellular Carcinoma Under 3 cm Treated by Percutaneous Tumor Destruction: Multicentric Phase 2 Test Evaluating the Impact of Adjuvant Chemotherapy by Intra-arterial Infusion of Idarubicin-lipiodol on the Hepatic Recurrence
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
First posted: 2019-11-26
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective multi-center phase II, randomized, unmasked comparative study (ratio 1:1), evaluating the efficacy of an adjuvant treatment by hepatic arterial chemo-infusion of Idarubicin-Lipiodol (experimental group) after percutaneous tumor ablation of hepatocellular carcinoma of size less than 3 cm, versus the absence of adjuvant treatment (standard group), on hepatic recurrence at 1 year.

It is planned to include 138 patients with hepatocellular carcinoma (CHC) less than 3 cm, non-metastatic, with cirrhosis graded A / B7 on Child Pugh scoring system, and receiving treatment by percutaneous tumor destruction.
Primary purpose: TREATMENT

Brief summary: The aim of this study is to test whether the realization of 3 courses of intra-arterial chemotherapy of idarubicin-lipiodol without embolization, administered non-selectively in the hepatic artery, following the percutaneous tumour ablation of a hepatocellular carcinoma, could constitute an effective adjuvant treatment to reduce the rates of local and intrahepatic distant recurrence and thus improve the survival without hepatic progression.

Detailed description: During this study percutaneous tumor destruction treatment with adjuvant chemotherapy (infusion of Idarubicin-Lipiodol intra-arterial hepatic) will be tested. The adjuvant chemotherapy is a minimally invasive technique. It consists of the administration of Idarubicin (Zavedos®, Pfizer) mixed with Lipiodol (Lipiodol Ultra-Fluid®, Guerbet) in the hepatic artery.The first course of treatment will be performed under general anesthesia at the same time as the percutaneous tumour ablation. The second and third cures will be performed under local anesthesia 3 and 6 weeks after percutaneous tumour ablation respectively. In the case of incomplete treatment during the percutaneous tumour ablation, the second intervention will be scheduled at the same time as the second intra-arterial chemotherapy treatment, under general anesthesia.

Eligibility criteria: Inclusion Criteria:

* Age above 18 and under 80 years-old
* Chronic or histologically proven stage F3 or F4 hepatopathy, with liver hardness ≥ 10 kPa, or with imaging morphology suggestive of cirrhosis or portal hypertension
* Child-Pugh score ≤ B7
* Patients whose biological parameters meet the following criteria:

  * Platelets \> 50,000 / mm3
  * Neutrophils \> 1000 / mm3
  * Prothrombin ratio \> 50%
  * Creatinemia \< 150 μmol / L
  * Total bilirubinemia \< 5 mg / dL
  * α-fetoprotein \< 200 ng / mL
* Performance level of 0 or 1 according to "World Health Organization Performance Status"
* Presence of a single hepatocellular carcinoma of less than 3 cm with typical imaging characteristics as recommended by the American Association for the Study of Liver Diseases (AASLD)
* Patient with an indication of percutaneous tumor ablation (radiofrequency or microwave) under ultrasound or tomodensitometric identification
* Absence of heart failure (Left Ventricular Ejection Fraction (LVEF) \> 50%)
* Women of childbearing age, using an effective method of contraception for the duration of treatment and at least 3 months after stopping the treatment.
* Male using an effective method of contraception throughout the treatment and at least 3 months after stopping the treatment

Exclusion Criteria:

* Presence on the initial imaging assessment of a macroscopic vascular invasion (portal or hepatic vein)
* Presence on initial imaging assessment of extrahepatic localization of hepatocellular carcinoma
* Presence of another untreated cancer
* Patients who previsouly received sphincterotomy or bilio-digestive anastomosis
* Contraindication to performing a general anesthesia
* Contraindication to performing an MRI scan
* Allergy to anthracyclines, iodine or gadolinium
* Contraindication to the injection of gadolinium-based contrast media.
* Contraindication to iodinated contrast agents
* Contraindication to Idarubicin (hypersensitivity to the active substance or excipients, severe heart disease, severe arrhythmia, severe renal or hepatic impairment, yellow fever vaccine or any other live attenuated vaccine for 6 months after discontinuation of chemotherapy, persistent myelosupressure, previous treatments with idarubicin and / or other anthracyclines or anthracenediones at maximum cumulative doses, mucositis, breastfeeding, uncontrolled infections, severe heart failure, myocardial infarction less than 6 months old).
* Contraindication to Lipiodol (Hypersensitivity, Hyperthyroidism, traumatic lesions, haemorrhage or recent bleeding)
* Patients who have already received or exceeded the recommended cumulative dose for anthracyclines (Idarubicin = 150 mg / m²)
* Patients who cannot temporarily stop their anticoagulant treatment or anti-platelet agent for the duration of the procedure
* Failure of endoscopic eradication of oesophageal varices of grade \> 1
* Inability to adhere to the protocol
* Simultaneous participation to another clinical trial
* Patients not covered by health insurance

Primary outcomes:
measure: The survival rate without hepatic recurrence at 1 year
timeFrame: 1 year
Secondary outcomes:
measure: The incidence rate of local tumor recurrence
timeFrame: 1 to 2 years
measure: The incidence rate of intrahepatic recurrence
timeFrame: 1 to 2 years
measure: The incidence rate of hepatic recurrence
timeFrame: 2 years
measure: Survival without hepatic recurrence
timeFrame: 2 years
measure: Rate of survival without hepatic recurrence
timeFrame: 1 to 2 years
measure: Overall survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Montpellier
country: France
facility: UH Montpellier
Study officials:
affiliation: University Hospital, Montpellier
name: Christophe CASSINOTTO
role: PRINCIPAL_INVESTIGATOR
References: