LifePearl-Doxo Pharmacokinetic (PK) Study

Not Applicable

Completed

• Conditions: Hepatocellular Carcinoma; HCC

• Registration Number: NCT02548780
• Lead Sponsor: Terumo Europe N.V.

Brief 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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2015-08-27
• Study First Submitted QC: 2015-09-10
• Study First Posted: 2015-09-14
• Study Start: 2016-04
• Primary Completion: 2018-10
• Study Completion: 2019-10-18
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-23
• Last Update Posted: 2020-01-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Adverse Events	1 month	Occurence of grade 3-4-5 treatment-related adverse events as Assessed by CTCAE v4.0.
Maximum Tolerated Dose (MTD) of Doxorubicine	1 month	Adverse Events (CTCAE v4.03 toxicity criteria) occurring within 28 days of the treatment. Grade ≥4 or Grade 3 in two patients at any one dose will mean the MTD has been achieved.
Peak Plasma Concentration (Cmax)	1 month	Maximum Plasma Concentration Doxorubicine
Area under the Curve (AUC)	1 month

Secondary Outcome Measures

Name	Time	Method
Angiographic Stasis	1 day	Ability to achieve stasis of bloodflow in the embolised arteries by angiographic assessment.
Response rate	3 months	Response rate assessed by Response Evaluation Criteria in Solid Tumors(RECIST) 1.1, EASL (European Association for the Study of the Liver) and mRECIST (modified RECIST) criteria 3 months after the first treatment
Total dose delivered	2 months	Sum of all doses Doxorubicine administered (maximum two chemoembolizations)
Time to Progression	24 months	Progression will be defined by the Barcelona Clinic Liver Cancer (BCLC)-refined RECIST
Overall Survival	24 months	The length of time from either the date of diagnosis or the start of treatment that patients diagnosed with the disease are still alive.
Progression Free Survival	24 months	The length of time during and after the treatment that a patient lives with the disease but it does not get worse.

Trial Locations

Locations (3)

Evgenidio Therapeftirio "Agia Trias"; 🇬🇷 Athens, Greece

Hospital Clínic i provincial de Barcelona; 🇪🇸 Barcelona, Spain

Centre Hospitalier Universitaire Vaudois; 🇨🇭 Lausanne, Switzerland