LifePearl-Doxo Pharmacokinetic (PK) Study

Pharmacokinetic Study in Patients With Unresectable Hepatocellular Carcinoma (HCC) Receiving Treatment With LifePearl Microspheres Loaded With Doxorubicin

The primary purpose of the study is to evaluate the pharmacokinetic profile, safety, and efficacy of LifePearl™ microspheres loaded with Doxorubicin in the treatment of unresectable HCC.

This is a multicentre, prospective dose escalation/PK study, designed to assess the clinical performance of LifePearl™ beads loaded with Doxorubicin in the primary treatment of unresectable HCC by chemoembolization. Data from this study will be used as supportive data post CE-mark approval.

The main objective of the study is to evaluate the safety and pharmacokinetic profile of LifePearl™ beads loaded with Doxorubicin in the treatment of patients with unresectable liver cancer (HCC) by chemoembolization. This will be measured as treatment-related complications and plasma levels of Doxorubicin in peripheral blood.

In addition, objective tumour response will be assessed by computed tomography or MRI.

Two cohorts of patients will be evaluated:

Cohort I to assess safety (dose escalation) and pharmacokinetic profile; Cohort II will assess pharmacokinetic profile, safety and efficacy with the doxorubicin dose determined with Cohort I.

Inclusion Criteria:

• Patient is at least 18 years old
• HCC diagnosed according to updated American Association for the Study of Liver Diseases (AASLD) or EASL-European Organization for Research and Treatment of Cancer (EORTC) criteria
• BCLC B patients or BCLC A patients not candidates for curative treatment (resection, transplantation, ablation) or who have failed/recurred after resection/ablation
• Tumor burden (located in one or two lobes) that can be sufficiently and selectively embolized with required dose of LifePearl loaded with doxorubicin
• Performance status (PS) 0
• Normal liver or compensated cirrhosis with preserved liver function (Child-Pugh A, score ≤ 6 points) without ascites in the absence of diuretic treatment
• Total bilirubin ≤2.0 mg/dl
• Adequate renal function (serum creatinine < 1.5 X ULN)
• Patient has provided written informed consent
• Patient is affiliated to social security or equivalent system (France only)

Exclusion Criteria:

• Patient previously treated with any intra-arterial therapy for HCC or sorafenib
• Eligible for curative treatment (resection/radiofrequency ablation (RFA), transplantation therapies);
• Advanced liver disease: Child-Pugh's B-C class or active gastrointestinal bleeding, encephalopathy. Bilirubin levels >2.0 mg/dl;
• Advanced tumoral disease: BCLC class C (vascular invasion -even segmental, extra-hepatic spread or cancer-related symptoms=PS of 1-2) or D class (WHO performance status 3 or 4)
• Patient with another primary tumor
• Patient with refractory ascites or on diuretic treatment
• Patient with history of biliary tree disease or biliary dilatation
• Portal vein thrombosis, porto-systemic shunt, hepatofugal blood flow or absent portal blood flow in the liver area to be treated
• Contraindication to multiphasic CT and MRI (e.g. allergy to contrast media);
• Any other contraindication for embolization or local doxorubicine treatment;
• Patient is currently participating in an investigational drug or device study that has not completed the primary endpoint or that clinically interferes with the current study endpoints
• In the Investigator's opinion patient has (a) co-morbid condition(s) that could limit the patient's ability to participate in the study, compliance with follow-up requirements or impact the scientific integrity of the study
• Pregnant or breast-feeding women
• Patient is under judicial protection (France only)