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

Hepatocellular Carcinoma Clinical Trial

— HiQuality  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01387932
• Other study ID #: HCC-P3-11-01
• Status: Terminated
• Phase: Phase 3
• Start date: June 2011
• Est. completion date: February 2021

Study information

• Verified date: November 2021
• Source: Merit Medical Systems, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 235
• Est. completion date: February 2021
• Est. primary completion date: February 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Device:
• HepaSphere/QuadraSphere Microspheres
HepaSphere/QuadraSphere Microspheres loaded with doxorubicin

Procedure:
• PVA, lipiodol, doxorubicin
Conventional TACE procedure using PVA, lipiodol and doxorubicin

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Merit Medical Systems, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  France,  Greece,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	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.