lifepearl-doxo pharmacokinetic (pk) study

Conditions: HCC; Hepatocellular Carcinoma

Summary: 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.

Eligibility criteria:
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)

Keywords: unresectable