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.

Study Overview

• Status: Completed
• Conditions: HCC; Hepatocellular Carcinoma
• Intervention / Treatment: Device: Chemoembolization; Other: Pharmacokinetics

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 Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece
    • Evgenidio Therapeftirio "Agia Trias"
• Spain
  • Barcelona, Spain
    • Hospital Clinic i Provincial de Barcelona
• Switzerland
  • Lausanne, Switzerland
    • Centre Hospitalier Universitaire Vaudois

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Chemoembolization + Pharmacokinetics; First cohort: Chemoembolization with Doxorubicin-loaded LifePearl™ microspheres (TACE): Escalation of dose loaded in microspheres from 75 mg to 150 mg. Pharmacokinetic testing in all patients. Second cohort: Chemoembolization with doxorubicin-loaded LifePearl™microspheres: microspheres loaded with maximum tolerated dose as established with dose escalation arm. Pharmacokinetic testing in all patients.

Device: Chemoembolization; First, an angiography of the celiac trunk, superior mesenteric artery and hepatic artery will be obtained by using a peripheral arterial approach. Arterial embolization will be performed through catheterization of intrahepatic arteries, as selectively as possible (tumor feeders, subsegmental, segmental). The size of the microcatheter must be consistent with the size of LifePearl beads used. Microspheres of 200 µm will be be used. They will be loaded with the appropriate dose of doxorubicin injectable solution, mixed with the contrast media and distributed according to the location of the HCC lesions. The endpoint of the procedure will be achieved end when stasis of the feeders is achieved and confirmed with angiography of the whole liver.; Other Names: Chemoembolization with LifePearl™ loaded with Doxorubicine; Other: Pharmacokinetics; Pharmacokinetic analysis will be performed in cohort I and II after the first treatment only. In addition to blood samples taken for biochemistry and haematology analysis, blood will be taken for pharmacokinetic assessment: Whole venous blood samples (6 ml in 2 tubes) will be taken from peripheral blood into ethylenediaminetetraacetic acid (EDTA) tubes prior to and at 5mins, 20mins, 40mins, 1h, 2h, 6h, 24h, 48h and 7 days after the procedure, and if needed (i.e. value at d7 is detectable) at 1 month (for safety assessment visit) either during hospital stay or in the outpatient clinic.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD) of Doxorubicine	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.	1 month
Peak Plasma Concentration (Cmax)	Maximum Plasma Concentration Doxorubicine	1 month
Adverse Events	Occurence of grade 3-4-5 treatment-related adverse events as Assessed by CTCAE v4.0.	1 month
Area under the Curve (AUC)		1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Angiographic Stasis	Ability to achieve stasis of bloodflow in the embolised arteries by angiographic assessment.	1 day
Total dose delivered	Sum of all doses Doxorubicine administered (maximum two chemoembolizations)	2 months
Response rate	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	3 months
Time to Progression	Progression will be defined by the Barcelona Clinic Liver Cancer (BCLC)-refined RECIST	24 months
Overall Survival	The length of time from either the date of diagnosis or the start of treatment that patients diagnosed with the disease are still alive.	24 months
Progression Free Survival	The length of time during and after the treatment that a patient lives with the disease but it does not get worse.	24 months

Collaborators and Investigators

• Sponsor: Terumo Europe N.V.
• Collaborators: Federation Francophone de Cancerologie Digestive; Fundacion Clinic per a la Recerca Biomédica
• Investigators: Principal Investigator: Jordi Bruix, MD, CLÍNIC BARCELONA Hospital Universitari, Spain

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): October 1, 2018
• Study Completion (Actual): October 18, 2019

Study Registration Dates

• First Submitted: August 27, 2015
• First Submitted That Met QC Criteria: September 10, 2015
• First Posted (Estimate): September 14, 2015

Study Record Updates

• Last Update Posted (Actual): January 27, 2020
• Last Update Submitted That Met QC Criteria: January 23, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: unresectable
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin
• Other Study ID Numbers: T125E2