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LifePearl-Doxo Pharmacokinetic (PK) Study

Primary Purpose

HCC, Hepatocellular Carcinoma

Status

Completed

Phase

Not Applicable

Locations

International

Study Type

Interventional

Intervention

Chemoembolization

Pharmacokinetics

About this trial

This is an interventional treatment trial for HCC focused on measuring unresectable

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Evgenidio Therapeftirio "Agia Trias"
Hospital Clínic i provincial de Barcelona
Centre Hospitalier Universitaire Vaudois

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Chemoembolization + Pharmacokinetics

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Peak Plasma Concentration (Cmax)

Maximum Plasma Concentration Doxorubicine

Adverse Events

Occurence of grade 3-4-5 treatment-related adverse events as Assessed by CTCAE v4.0.

Area under the Curve (AUC)

Secondary Outcome Measures

Angiographic Stasis

Ability to achieve stasis of bloodflow in the embolised arteries by angiographic assessment.

Total dose delivered

Sum of all doses Doxorubicine administered (maximum two chemoembolizations)

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

Time to Progression

Progression will be defined by the Barcelona Clinic Liver Cancer (BCLC)-refined RECIST

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.

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.

Full Information

NCT ID

NCT02548780

First Posted

August 27, 2015

Last Updated

January 23, 2020

Sponsor

Terumo Europe N.V.

Collaborators

Federation Francophone de Cancerologie Digestive, Fundacion Clinic per a la Recerca Biomédica

1. Study Identification

Unique Protocol Identification Number

NCT02548780

Brief Title

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

2. Study Status

Record Verification Date

January 2020

Overall Recruitment Status

Completed

Study Start Date

April 2016 (Actual)

Primary Completion Date

October 2018 (Actual)

Study Completion Date

October 18, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Terumo Europe N.V.

Collaborators

Federation Francophone de Cancerologie Digestive, Fundacion Clinic per a la Recerca Biomédica

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HCC, Hepatocellular Carcinoma

Keywords

unresectable

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Chemoembolization + Pharmacokinetics

Arm Type

Experimental

Arm Description

Intervention Type

Device

Intervention Name(s)

Chemoembolization

Other Intervention Name(s)

Chemoembolization with LifePearl™ loaded with Doxorubicine

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Pharmacokinetics

Intervention Description

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.

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose (MTD) of Doxorubicine

Description

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.

Time Frame

1 month

Title

Peak Plasma Concentration (Cmax)

Description

Maximum Plasma Concentration Doxorubicine

Time Frame

1 month

Title

Adverse Events

Description

Occurence of grade 3-4-5 treatment-related adverse events as Assessed by CTCAE v4.0.

Time Frame

1 month

Title

Area under the Curve (AUC)

Time Frame

1 month

Secondary Outcome Measure Information:

Title

Angiographic Stasis

Description

Ability to achieve stasis of bloodflow in the embolised arteries by angiographic assessment.

Time Frame

1 day

Title

Total dose delivered

Description

Sum of all doses Doxorubicine administered (maximum two chemoembolizations)

Time Frame

2 months

Title

Response rate

Description

Time Frame

3 months

Title

Time to Progression

Description

Progression will be defined by the Barcelona Clinic Liver Cancer (BCLC)-refined RECIST

Time Frame

24 months

Title

Overall Survival

Description

The length of time from either the date of diagnosis or the start of treatment that patients diagnosed with the disease are still alive.

Time Frame

24 months

Title

Progression Free Survival

Description

The length of time during and after the treatment that a patient lives with the disease but it does not get worse.

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jordi Bruix, MD

Organizational Affiliation

CLÍNIC BARCELONA Hospital Universitari, Spain

Official's Role

Principal Investigator

Facility Information:

Facility Name

Evgenidio Therapeftirio "Agia Trias"

City

Athens

Country

Greece

Facility Name

Hospital Clínic i provincial de Barcelona

City

Barcelona

Country

Spain

Facility Name

Centre Hospitalier Universitaire Vaudois

City

Lausanne

Country

Switzerland

12. IPD Sharing Statement

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LifePearl-Doxo Pharmacokinetic (PK) Study

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