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

Phase 3 Prospective, Randomized, Blinded, and Controlled Investigation of HepaSphere/QuadraSphere Microspheres for Delivery of Doxorubicin for the Treatment of Hepatocellular Carcinoma

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.

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Device: HepaSphere/QuadraSphere Microspheres; Procedure: PVA, lipiodol, 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.

• Study Type: Interventional
• Enrollment (Actual): 235
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • University Hospitals K.U. Leuven (Dept of Hematology)
• France
  • Bordeaux, France, 33075
    • Hospital Saint Andre
  • Villejuif cedex, France, 94804
    • Hospital Paul Brousse
• Greece
  • Athens, Greece, 115 28
    • Evgenidion University Hospital
• Italy
  • Cuneo, Italy, 12100
    • S. Croce e Carle Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • University of Alabama at Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85711
      • Tuscon Medical Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Greater Arkansas Veterans Healthcare
  • California
    • Los Angeles, California, United States, 90095
      • UCLA
    • Los Angeles, California, United States, 90073
      • VA Greater Los Angeles Healthcare System
    • Palo Alto, California, United States, 94304
      • Palo Alto Veterans Institute for Research
    • Stanford, California, United States, 94305
      • Stanford University
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Massachusetts
    • Boston, Massachusetts, United States, 35209
      • Massachusetts General Hospital
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Healthcare
    • Pittsburgh, Pennsylvania, United States, 15261
      • VA Pittsburgh Healthcare System
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • MUSC Medical Center (Medical University of South Carolina)
  • Texas
    • San Antonio, Texas, United States, 78229
      • UT Health and Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: HepaSphere/QuadraSphere TACE	Device: HepaSphere/QuadraSphere Microspheres; HepaSphere/QuadraSphere Microspheres loaded with doxorubicin
ACTIVE_COMPARATOR: Conventional TACE	Procedure: PVA, lipiodol, doxorubicin; Conventional TACE procedure using PVA, lipiodol and doxorubicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Overall Survival	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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rates (ORR)	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.	Study was terminated early so analysis of additional outcome(s) were not possible.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of TACE-Related Adverse Events in Subjects Treated With HepaSphere/QuadraSphere vs Subjects Treated With Conventional TACE.	The number of TACE- Related adverse events experienced by subjects treated with HepaSphere/QuadraSphere will be compared to the number of TACE-related adverse events experienced by subjects treated with conventional TACE. Adverse events were recorded for treated subjects from the date of randomization up to and including 30 days post the last study MRI.	30 days

Collaborators and Investigators

• Sponsor: Merit Medical Systems, Inc.
• Investigators: Principal Investigator: Michael Soulen, MD, University of Pennsylvania; Study Chair: Riccardo Lencioni, MD, Independent Radiology Panel; Study Chair: Josep Llovet, MD, Data Safety Monitoring Board

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2011
• Primary Completion (ACTUAL): February 1, 2021
• Study Completion (ACTUAL): February 1, 2021

Study Registration Dates

• First Submitted: April 11, 2011
• First Submitted That Met QC Criteria: July 5, 2011
• First Posted (ESTIMATE): July 6, 2011

Study Record Updates

• Last Update Posted (ACTUAL): November 30, 2021
• Last Update Submitted That Met QC Criteria: November 2, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Doxorubicin; Hepatocellular carcinoma; TACE; HepaSphere Microspheres; QuadraSphere Microspheres
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Ethiodized Oil
• Other Study ID Numbers: HCC-P3-11-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: Yes