LifePearl-Doxo Pharmacokinetic (PK) Study

NCT02548780 | Completed DMC

• 1 other identifier: T125E2
• Study Type: interventional
• Target: 15
• Locations: 3 countries
• Sites: 3

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.

Conditions

HCC; Hepatocellular Carcinoma

Keywords

unresectable

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (6)

• Angiographic Stasis

  1 day

• Total dose delivered

  2 months

• Response rate

  3 months

• Time to Progression

  24 months

• Overall Survival

  24 months

Study Arms (1)

Chemoembolization + Pharmacokinetics

EXPERIMENTAL

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; Other: Pharmacokinetics

Interventions

Chemoembolization DEVICE

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.

Also known as: Chemoembolization with LifePearl™ loaded with Doxorubicine

Chemoembolization + Pharmacokinetics

Pharmacokinetics OTHER

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.

Chemoembolization + Pharmacokinetics

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Terumo Europe N.V.: lead
• Federation Francophone de Cancerologie Digestive: collaborator
• Fundacion Clinic per a la Recerca Biomédica: collaborator

Study Sites (3)

Evgenidio Therapeftirio "Agia Trias"

Athens, Greece

Location

Hospital Clínic i provincial de Barcelona

Barcelona, Spain

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Chemoembolization, Therapeutic; Pharmacokinetics

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Embolization, Therapeutic; Hemostatic Techniques; Therapeutics; Therapeutic Occlusion; Metabolism; Pharmacological and Toxicological Phenomena; Physiological Phenomena

Study Officials

• Jordi Bruix, MD

  CLÍNIC BARCELONA Hospital Universitari, Spain

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2015
• First Posted: September 14, 2015
• Study Start: April 1, 2016
• Primary Completion: October 1, 2018
• Study Completion: October 18, 2019
• Last Updated: January 27, 2020

Record last verified: 2020-01

Locations

GR (1); CH (1); ES (1)