HepaSphere/Quadrasphere Microspheres for Delivery of Doxorubicin for the Treatment of Hepatocellular Cancer

NCT ID: NCT01387932

Last Updated: 2021-11-30

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

235 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-06-30

Study Completion Date

2021-02-28

Brief Summary

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The purpose of this study is to evaluate overall survival in patients diagnosed with hepatocellular cancer (HCC) treated with HepaSphere/QuadraSphere Microspheres loaded with chemotherapeutic agent doxorubicin compared to conventional transarterial chemoembolization with particle PVA, lipiodol, and doxorubicin.

Detailed Description

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This phase three, interventional, and prospective study consists of a patient population that has advanced liver cancer (hepatocellular cancer \[HCC\]) that cannot be removed by standard therapies such as surgical removal, liver transplant, and/or ablation.

Embolics and drug eluting embolics are being used by interventional radiologists to try and shrink or kill the tumor area.

Patients that met eligibility criteria, wanted to participate in the study, and signed the informed consent form (ICF) made up the study subject population. Subjects were randomized on a 1:1 basis (subjects were blinded to arm they were randomized to).

Post randomization and within four weeks of the first chemoembolization procedure all subjects had a baseline MRI. Following, the first chemoembolization procedure (hqTACE or cTACE) or 'cycle' was completed. Subjects can (per protocol) receive up to 3 TACE cycles. Within 4 weeks after any TACE cycle, an MRI and labs should be conducted/collected to evaluate disease status (reduction vs progression) and measure treated lesions. Any residual disease that is present after after the first TACE will undergo the next TACE cycle (maximum of three). However, if the liver MRI shows a complete response (absence of HCC) then no additional TACE procedures are performed and the subject is followed for survival.

Conditions

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Hepatocellular Carcinoma

Keywords

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Hepatocellular carcinoma TACE HepaSphere Microspheres QuadraSphere Microspheres Doxorubicin

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants are randomized 1:1 to receive either 1. A Conventional TACE (Trans Arterial Chemoembolization) procedure using PVA, lipiodol and doxorubicin (cTACE), or 2. HepaSphere/QuadraSphere Microspheres loaded with doxorubicin for Trans Arterial Chemoembolization (hqTACE). Participants in both treatment arms will be followed for overall survival, the primary study endpoint.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors
Participants are blinded to the treatment they are randomized to (cTACE or hqTACE). Central Reviewers (two interventional radiologists) will evaluate study participant's liver MRIs to assess the tumor response. The Central Reviewers will be blinded to the treatment the participant received.

Study Groups

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HepaSphere/QuadraSphere TACE

HepaSphere/QuadraSphere TACE

Group Type EXPERIMENTAL

HepaSphere/QuadraSphere Microspheres

Intervention Type DEVICE

HepaSphere/QuadraSphere Microspheres loaded with doxorubicin

Conventional TACE

Conventional TACE

Group Type ACTIVE_COMPARATOR

PVA, lipiodol, doxorubicin

Intervention Type PROCEDURE

Conventional TACE procedure using PVA, lipiodol and doxorubicin

Interventions

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HepaSphere/QuadraSphere Microspheres

HepaSphere/QuadraSphere Microspheres loaded with doxorubicin

Intervention Type DEVICE

PVA, lipiodol, doxorubicin

Conventional TACE procedure using PVA, lipiodol and doxorubicin

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

1. Age 18 or older
2. Patient has signed informed consent
3. Patient must have a diagnosis of hepatocellular cancer confirmed by at least one of the following:

i. Histological confirmation ii. Magnetic resonance imaging (MRI) result with early enhancement and delayed enhancement washout of at least one solid liver lesion \> 1 cm. Patient must also have evidence of cirrhosis or have chronic hepatitis B.

iii. Contrast enhanced computed tomography (CT) with early enhancement and delayed enhancement washout of at least one solid liver lesion \> 1cm. Patient must also have evidence of cirrhosis or have chronic hepatitis B.

d. Patient must not be suitable for treatment by resection or percutaneous ablation at time of study entry.

Patients not suitable for ablation due to lesion location may be enrolled

e. Patient MUST meet at least ONE of the following criteria:

i. Stage Child-Pugh B 7 ii. Recurrent HCC iii.Performance status ECOG 1

f. Patient has a life expectancy of at least 6 months

g. Absence of occlusive thrombus to the main portal trunk

Exclusion Criteria

If patients meet any of the following criteria they may not be entered into the study:

1. Current or previous treatment with chemo- or radiation therapy or sorafenib
2. Previous treatment with any form of transarterial embolization for HCC
3. Patients with current or history of any other cancer except non-melanomatous skin cancer
4. Female patients who are pregnant, breastfeeding, or premenopausal and not using an effective method of contraceptive
5. Performance status ECOG \> 2
6. Child-Pugh scores \>7
7. Active gastrointestinal bleeding
8. Evidence of uncorrectable bleeding diathesis
9. Extra-hepatic spread of the HCC
10. Total Bilirubin \> 3 mg/dL
11. \>50% tumor involvement of the liver
12. Infiltrative or diffuse HCC
13. Encephalopathy not adequately controlled medically
14. Presence of ascites not controlled medically
15. Presence of medically relevant localized or systemic infection, other than hepatitis B, C, D, E or G
16. Any contraindication for MRI (eg. metallic implants)
17. Allergy to contrast media that cannot be managed with prophylaxis
18. Allergy to iodized oil
19. Any contraindication to arteriography
20. Any contraindication for doxorubicin administration, including the following:

i. White Blood Cell count (WBC) \<3000 cells/mm₃

ii. Absolute Neutrophil \<1500 cells/mm₃

iii. Cardiac ejection fraction \<50%

iv. Other condition deemed exclusionary by physician

u. Any contraindication for hepatic embolization, including the following:

i. Porto-systemic shunt, or an arteriovenous shunt that cannot be adequately closed prior to chemoembolization

ii. Hepatofugal blood flow

iii. Serum creatinine \> 2mg/dL

iv. Uncorrectable impaired clotting

1. Platelet \<50,000/mm₃
2. International Normalized Ratio (INR) \> 1.4
3. Activated Prothrombin Time (aPTT) less than 21 or greater than 40

v. AST \> 5X upper limit of normal for lab

vi. ALT \> 5X upper limit of normal for lab
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merit Medical Systems, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Soulen, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Riccardo Lencioni, MD

Role: STUDY_CHAIR

Independent Radiology Panel

Josep Llovet, MD

Role: STUDY_CHAIR

Data Safety Monitoring Board

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Tuscon Medical Center

Tucson, Arizona, United States

Site Status

Greater Arkansas Veterans Healthcare

Little Rock, Arkansas, United States

Site Status

VA Greater Los Angeles Healthcare System

Los Angeles, California, United States

Site Status

UCLA

Los Angeles, California, United States

Site Status

Palo Alto Veterans Institute for Research

Palo Alto, California, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

Tampa General Hospital

Tampa, Florida, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Albany Medical Center

Albany, New York, United States

Site Status

Mount Sinai Medical Center

New York, New York, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Albert Einstein Healthcare

Philadelphia, Pennsylvania, United States

Site Status

VA Pittsburgh Healthcare System

Pittsburgh, Pennsylvania, United States

Site Status

MUSC Medical Center (Medical University of South Carolina)

Charleston, South Carolina, United States

Site Status

UT Health and Science Center

San Antonio, Texas, United States

Site Status

University Hospitals K.U. Leuven (Dept of Hematology)

Leuven, , Belgium

Site Status

Hospital Saint Andre

Bordeaux, , France

Site Status

Hospital Paul Brousse

Villejuif, , France

Site Status

Evgenidion University Hospital

Athens, , Greece

Site Status

S. Croce e Carle Hospital

Cuneo, , Italy

Site Status

Countries

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Austria Egypt United States Belgium France Greece Italy

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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HCC-P3-11-01

Identifier Type: -

Identifier Source: org_study_id