The Impact on Hepatic Recurrence After Adjuvant Chemotherapy With Intraarterial Infusion of Idarubicin-Lipiodol

NCT04178642 | Withdrawn Phase 2 DMC

• 3 other identifiers: RECHMPL19_00732019-001362-157773
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• The survival rate without hepatic recurrence at 1 year

  Hepatic recurrence will be defined as the appearance on at least one hepatic MRI with gadolinium injection of a large diameter tumor site at least greater than 10 mm, and presenting characteristics of CHC (hyper vascularization at arterial time and washing at portal or late time), either at the edge of the percutaneous tumor destruction site (= local recurrence) or at a distance from the percutaneous tumor destruction site (= intrahepatic recurrence distant), or both, after at least one liver MRI scan with gadolinium injection showed the absence of tumor residues. Lesions of more than 10 mm that do not present with the typical CHC enhancement described above will be considered CHCs if they have a growth in size of at least 1 cm on successive controls.

  1 year

Secondary Outcomes (6)

• The incidence rate of local tumor recurrence

  1 to 2 years

• The incidence rate of intrahepatic recurrence

  1 to 2 years

• The incidence rate of hepatic recurrence

  2 years

• Survival without hepatic recurrence

  2 years

• Rate of survival without hepatic recurrence

  1 to 2 years

Study Arms (2)

(experimental group)

EXPERIMENTAL

Evaluating the efficacy of an adjuvant treatment by hepatic arterial chemo-infusion of Idarubicin-Lipiodol (experimental group)

Drug: percutaneous destruction of the tumor + Idarubicin-Lipiodol treatment

(standard group)

ACTIVE COMPARATOR

The absence of adjuvant treatment (standard group).

Procedure: Percutaneous destruction of the tumor

Interventions

percutaneous destruction of the tumor + Idarubicin-Lipiodol treatment DRUG

Patients will receive the standard treatment protocol consisting of a percutaneous destruction of the tumor. In addition they will receive an adjuvant treatment by hepatic arterial chemo-infusion of Idarubicin (Zavedos®, Pfizer), which is an anthracycline antineoplastic agent, mixed with Lipiodol (Lipiodol Ultra-Fluid®, Guerbet), which is a contrast agent.

(experimental group)

Percutaneous destruction of the tumor PROCEDURE

Patients will received the standard treatment protocol consisting of a percutaneous destruction of the tumor.

(standard group)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (1)

UH Montpellier

Montpellier, France

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Christophe CASSINOTTO

  University Hospital, Montpellier

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 4, 2019
• First Posted: November 26, 2019
• Study Start: September 22, 2020
• Primary Completion: July 14, 2021
• Study Completion: July 14, 2021
• Last Updated: December 14, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)