Clinical trial NCT01387932: HepaSphere/Quadrasphere Microspheres for Delivery of Doxorubicin for the Treatment of Hepatocellular Cancer
Official title: Phase 3 Prospective, Randomized, Blinded, and Controlled Investigation of HepaSphere/QuadraSphere Microspheres for Delivery of Doxorubicin for the Treatment of Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular carcinoma
TACE
HepaSphere Microspheres
QuadraSphere Microspheres
Doxorubicin
Lead sponsor: Merit Medical Systems, Inc.
Sponsor class: INDUSTRY
First posted: 2011-07-06
Enrollment: 235
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Median Overall Survival
timeFrame: 2 years
Secondary outcomes:
measure: Objective Response Rates (ORR)
timeFrame: Study was terminated early so analysis of additional outcome(s) were not possible.
Other outcomes:
measure: Number of TACE-Related Adverse Events in Subjects Treated With HepaSphere/QuadraSphere vs Subjects Treated With Conventional TACE.
timeFrame: 30 days
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: Tuscon Medical Center
state: Arizona
city: Little Rock
country: United States
facility: Greater Arkansas Veterans Healthcare
state: Arkansas
city: Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Palo Alto
country: United States
facility: Palo Alto Veterans Institute for Research
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Healthcare
state: Pennsylvania
city: Pittsburgh
country: United States
facility: VA Pittsburgh Healthcare System
state: Pennsylvania
city: Charleston
country: United States
facility: MUSC Medical Center (Medical University of South Carolina)
state: South Carolina
city: San Antonio
country: United States
facility: UT Health and Science Center
state: Texas
city: Leuven
country: Belgium
facility: University Hospitals K.U. Leuven (Dept of Hematology)
city: Bordeaux
country: France
facility: Hospital Saint Andre
city: Villejuif cedex
country: France
facility: Hospital Paul Brousse
city: Athens
country: Greece
facility: Evgenidion University Hospital
city: Cuneo
country: Italy
facility: S. Croce e Carle Hospital
Study officials:
affiliation: University of Pennsylvania
name: Michael Soulen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Independent Radiology Panel
name: Riccardo Lencioni, MD
role: STUDY_CHAIR
affiliation: Data Safety Monitoring Board
name: Josep Llovet, MD
role: STUDY_CHAIR
References: