Clinical trial NCT02548780: LifePearl-Doxo Pharmacokinetic (PK) Study
Official title: Pharmacokinetic Study in Patients With Unresectable Hepatocellular Carcinoma (HCC) Receiving Treatment With LifePearl Microspheres Loaded With Doxorubicin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HCC
Hepatocellular Carcinoma
Keywords: unresectable
Lead sponsor: Terumo Europe N.V.
Sponsor class: INDUSTRY
Collaborators: name: Federation Francophone de Cancerologie Digestive
name: Fundacion Clinic per a la Recerca Biomédica
First posted: 2015-09-14
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Doxorubicine
timeFrame: 1 month
measure: Peak Plasma Concentration (Cmax)
timeFrame: 1 month
measure: Adverse Events
timeFrame: 1 month
measure: Area under the Curve (AUC)
timeFrame: 1 month
Secondary outcomes:
measure: Angiographic Stasis
timeFrame: 1 day
measure: Total dose delivered
timeFrame: 2 months
measure: Response rate
timeFrame: 3 months
measure: Time to Progression
timeFrame: 24 months
measure: Overall Survival
timeFrame: 24 months
measure: Progression Free Survival
timeFrame: 24 months
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Evgenidio Therapeftirio "Agia Trias"
city: Barcelona
country: Spain
facility: Hospital Clínic i provincial de Barcelona
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
Study officials:
affiliation: CLÍNIC BARCELONA Hospital Universitari, Spain
name: Jordi Bruix, MD
role: PRINCIPAL_INVESTIGATOR
References: