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

Phase 3

Terminated

Conditions: Hepatocellular Carcinoma

Interventions: Device: HepaSphere/QuadraSphere Microspheres
Procedure: PVA, lipiodol, doxorubicin

Registration Number: NCT01387932

Lead Sponsor: Merit Medical Systems, Inc.

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 235

Inclusion Criteria

Patients must meet all of the following inclusion criteria in order to be entered into the study:

Age 18 or older
Patient has signed informed consent
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:

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

Platelet <50,000/mm₃
International Normalized Ratio (INR) > 1.4
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HepaSphere/QuadraSphere TACE	HepaSphere/QuadraSphere Microspheres	HepaSphere/QuadraSphere TACE
Conventional TACE	PVA, lipiodol, doxorubicin	Conventional TACE

Primary Outcome Measures

Name	Time	Method
Median Overall Survival	2 years	Median overall survival will be calculated using the Intent-to-Treat (ITT) population in each treatment arm when the last subject has completed two years of follow up after their first study TACE procedure. Per protocol, study subjects were followed for survival until death or deemed lost to follow up. All deaths are reported within safety.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rates (ORR)	Study was terminated early so analysis of additional outcome(s) were not possible.	The Objective Response Rate will be calculated for the ITT population by adding the number of participants that were determined to have complete or partial response (utilizing mRECIST criteria) and dividing by the number of ITT participants.

Trial Locations

Locations (23): Albert Einstein Healthcare
🇺🇸
Philadelphia, Pennsylvania, United States
Greater Arkansas Veterans Healthcare
🇺🇸
Little Rock, Arkansas, United States
Mount Sinai Medical Center
🇺🇸
New York, New York, United States
Hospital Paul Brousse
🇫🇷
Villejuif cedex, France
University Hospitals K.U. Leuven (Dept of Hematology)
🇧🇪
Leuven, Belgium
VA Pittsburgh Healthcare System
🇺🇸
Pittsburgh, Pennsylvania, United States
UCLA
🇺🇸
Los Angeles, California, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
Albany Medical Center
🇺🇸
Albany, New York, United States
Hospital Saint Andre
🇫🇷
Bordeaux, France
Hospital of the University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
UT Health and Science Center
🇺🇸
San Antonio, Texas, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
VA Greater Los Angeles Healthcare System
🇺🇸
Los Angeles, California, United States
Stanford University
🇺🇸
Stanford, California, United States
MUSC Medical Center (Medical University of South Carolina)
🇺🇸
Charleston, South Carolina, United States
Evgenidion University Hospital
🇬🇷
Athens, Greece
S. Croce e Carle Hospital
🇮🇹
Cuneo, Italy
Georgetown University Hospital
🇺🇸
Washington, District of Columbia, United States
Tuscon Medical Center
🇺🇸
Tucson, Arizona, United States
Palo Alto Veterans Institute for Research
🇺🇸
Palo Alto, California, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Tampa General Hospital
🇺🇸
Tampa, Florida, United States