Trial Outcomes & Findings for HepaSphere/Quadrasphere Microspheres for Delivery of Doxorubicin for the Treatment of Hepatocellular Cancer (NCT NCT01387932)

Last Updated: 2021-11-30

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

235 participants

Primary outcome timeframe

2 years

Results posted on

2021-11-30

Participant Flow

Study enrollment began in June 2011 and ended in May 2017.

Of the 235 subjects that were randomized, 224 were treated. Eleven (11) randomized subjects did not receive treatment, 5 of which were not treated at the investigators discretion and 6 that withdrew consent.

Participant milestones

Participant milestones
Measure	HepaSphere/QuadraSphere TACE HepaSphere/QuadraSphere TACE Transarterial chemoembolization in participants with localized, non-resectable hepatocellular carcinoma utilizing HepaSphere/QuadraSphere Microspheres loaded with doxorubicin.	Conventional TACE Conventional TACE Transarterial chemoembolization in participants with localized, non-resectable hepatocellular carcinoma utilizing PVA, lipiodol, doxorubicin.
Randomized and Treated STARTED	118	117
Randomized and Treated COMPLETED	111	113
Randomized and Treated NOT COMPLETED	7	4
Completion of TACE Cycle STARTED	111	113
Completion of TACE Cycle COMPLETED	111	113
Completion of TACE Cycle NOT COMPLETED	0	0
Survival Follow-up STARTED	111	113
Survival Follow-up COMPLETED	27	23
Survival Follow-up NOT COMPLETED	84	90

Reasons for withdrawal

Reasons for withdrawal
Measure	HepaSphere/QuadraSphere TACE HepaSphere/QuadraSphere TACE Transarterial chemoembolization in participants with localized, non-resectable hepatocellular carcinoma utilizing HepaSphere/QuadraSphere Microspheres loaded with doxorubicin.	Conventional TACE Conventional TACE Transarterial chemoembolization in participants with localized, non-resectable hepatocellular carcinoma utilizing PVA, lipiodol, doxorubicin.
Randomized and Treated Physician Decision	3	2
Randomized and Treated Withdrawal by Subject	4	2
Survival Follow-up Liver Transplant	24	28
Survival Follow-up Additional treatment excluding liver transplant	52	53
Survival Follow-up Withdrawal by Subject	2	4
Survival Follow-up Lost to Follow-up	6	5

Baseline Characteristics

The Analysis Population is the 224 treated subjects and not the 235 randomized subjects, as the 11 subjects either withdrew consent or did not receive any study treatments as they were deemed ineligible by the treating investigator.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HepaSphere/QuadraSphere TACE n=118 Participants HepaSphere/QuadraSphere TACE HepaSphere/QuadraSphere Microspheres: HepaSphere/QuadraSphere Microspheres loaded with doxorubicin	Conventional TACE n=117 Participants Conventional TACE PVA, lipiodol, doxorubicin: Conventional TACE procedure using PVA, lipiodol and doxorubicin	Total n=235 Participants Total of all reporting groups
Age, Continuous	64.0 years STANDARD_DEVIATION 8.95 • n=118 Participants	64.2 years STANDARD_DEVIATION 8.40 • n=117 Participants	64.1 years STANDARD_DEVIATION 8.66 • n=235 Participants
Sex: Female, Male Female	24 Participants n=118 Participants	20 Participants n=117 Participants	44 Participants n=235 Participants
Sex: Female, Male Male	94 Participants n=118 Participants	97 Participants n=117 Participants	191 Participants n=235 Participants
Race/Ethnicity, Customized RACE (NIH/OMB) · Asian	8 Participants n=118 Participants	6 Participants n=117 Participants	14 Participants n=235 Participants
Race/Ethnicity, Customized RACE (NIH/OMB) · Native Hawaiian or Pacific Islander	0 Participants n=118 Participants	1 Participants n=117 Participants	1 Participants n=235 Participants
Race/Ethnicity, Customized RACE (NIH/OMB) · Black or African American	8 Participants n=118 Participants	9 Participants n=117 Participants	17 Participants n=235 Participants
Race/Ethnicity, Customized RACE (NIH/OMB) · White	95 Participants n=118 Participants	96 Participants n=117 Participants	191 Participants n=235 Participants
Race/Ethnicity, Customized RACE (NIH/OMB) · More than one race	2 Participants n=118 Participants	1 Participants n=117 Participants	3 Participants n=235 Participants
Race/Ethnicity, Customized RACE (NIH/OMB) · Unknown or Not Reported	5 Participants n=118 Participants	4 Participants n=117 Participants	9 Participants n=235 Participants
Region of Enrollment Greece	25 Participants n=111 Participants • The Analysis Population is the 224 treated subjects and not the 235 randomized subjects, as the 11 subjects either withdrew consent or did not receive any study treatments as they were deemed ineligible by the treating investigator.	24 Participants n=113 Participants • The Analysis Population is the 224 treated subjects and not the 235 randomized subjects, as the 11 subjects either withdrew consent or did not receive any study treatments as they were deemed ineligible by the treating investigator.	49 Participants n=224 Participants • The Analysis Population is the 224 treated subjects and not the 235 randomized subjects, as the 11 subjects either withdrew consent or did not receive any study treatments as they were deemed ineligible by the treating investigator.
Region of Enrollment Belgium	2 Participants n=111 Participants • The Analysis Population is the 224 treated subjects and not the 235 randomized subjects, as the 11 subjects either withdrew consent or did not receive any study treatments as they were deemed ineligible by the treating investigator.	2 Participants n=113 Participants • The Analysis Population is the 224 treated subjects and not the 235 randomized subjects, as the 11 subjects either withdrew consent or did not receive any study treatments as they were deemed ineligible by the treating investigator.	4 Participants n=224 Participants • The Analysis Population is the 224 treated subjects and not the 235 randomized subjects, as the 11 subjects either withdrew consent or did not receive any study treatments as they were deemed ineligible by the treating investigator.
Region of Enrollment United States	78 Participants n=111 Participants • The Analysis Population is the 224 treated subjects and not the 235 randomized subjects, as the 11 subjects either withdrew consent or did not receive any study treatments as they were deemed ineligible by the treating investigator.	79 Participants n=113 Participants • The Analysis Population is the 224 treated subjects and not the 235 randomized subjects, as the 11 subjects either withdrew consent or did not receive any study treatments as they were deemed ineligible by the treating investigator.	157 Participants n=224 Participants • The Analysis Population is the 224 treated subjects and not the 235 randomized subjects, as the 11 subjects either withdrew consent or did not receive any study treatments as they were deemed ineligible by the treating investigator.
Region of Enrollment Italy	4 Participants n=111 Participants • The Analysis Population is the 224 treated subjects and not the 235 randomized subjects, as the 11 subjects either withdrew consent or did not receive any study treatments as they were deemed ineligible by the treating investigator.	4 Participants n=113 Participants • The Analysis Population is the 224 treated subjects and not the 235 randomized subjects, as the 11 subjects either withdrew consent or did not receive any study treatments as they were deemed ineligible by the treating investigator.	8 Participants n=224 Participants • The Analysis Population is the 224 treated subjects and not the 235 randomized subjects, as the 11 subjects either withdrew consent or did not receive any study treatments as they were deemed ineligible by the treating investigator.
Region of Enrollment France	2 Participants n=111 Participants • The Analysis Population is the 224 treated subjects and not the 235 randomized subjects, as the 11 subjects either withdrew consent or did not receive any study treatments as they were deemed ineligible by the treating investigator.	4 Participants n=113 Participants • The Analysis Population is the 224 treated subjects and not the 235 randomized subjects, as the 11 subjects either withdrew consent or did not receive any study treatments as they were deemed ineligible by the treating investigator.	6 Participants n=224 Participants • The Analysis Population is the 224 treated subjects and not the 235 randomized subjects, as the 11 subjects either withdrew consent or did not receive any study treatments as they were deemed ineligible by the treating investigator.

PRIMARY outcome

Timeframe: 2 years

Population: The analysis populations for both the HepaSphere/QuadraSphere TACE (hqTACE) and conventional TACE (cTACE) arms included all subjects with HCC that received one or more protocol specified TACE procedures.

Outcome measures

Outcome measures
Measure	HepaSphere/QuadraSphere TACE n=27 Participants HepaSphere/QuadraSphere TACE HepaSphere/QuadraSphere Microspheres: HepaSphere/QuadraSphere Microspheres loaded with doxorubicin	Conventional TACE n=23 Participants Conventional TACE PVA, lipiodol, doxorubicin: Conventional TACE procedure using PVA, lipiodol and doxorubicin
Median Overall Survival	9.0 Months Interval 8.02 to 9.99	7.0 Months Interval 3.39 to 10.61

SECONDARY outcome

Timeframe: Study was terminated early so analysis of additional outcome(s) were not possible.

Population: Data was not collected.

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 30 days

Population: Analysis populations were: 1. All subjects treated with HepaSphere/QuadraSphere TACE and 2. All 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.

Outcome measures

Outcome measures
Measure	HepaSphere/QuadraSphere TACE n=111 Participants HepaSphere/QuadraSphere TACE HepaSphere/QuadraSphere Microspheres: HepaSphere/QuadraSphere Microspheres loaded with doxorubicin	Conventional TACE n=113 Participants Conventional TACE PVA, lipiodol, doxorubicin: Conventional TACE procedure using PVA, lipiodol and doxorubicin
Number of TACE-Related Adverse Events in Subjects Treated With HepaSphere/QuadraSphere vs Subjects Treated With Conventional TACE.	149 A TACE related Adverse Event	164 A TACE related Adverse Event

Adverse Events

HepaSphere/QuadraSphere TACE

Serious events: 23 serious events

Other events: 86 other events

Deaths: 100 deaths

Conventional TACE

Serious events: 21 serious events

Other events: 87 other events

Deaths: 93 deaths

Serious adverse events

Other adverse events

Additional Information

Vicky Brunk RN, Vice President, Medical Affairs, Merit Medical

Merit Medical Systems, Inc.

Phone: +1 (717) 873-3309

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	HepaSphere/QuadraSphere TACE n=111 participants at risk HepaSphere/QuadraSphere TACE Transarterial chemoembolization in participants with localized, non-resectable hepatocellular carcinoma utilizing HepaSphere/QuadraSphere Microspheres loaded with doxorubicin.	Conventional TACE n=113 participants at risk Conventional TACE Transarterial chemoembolization in participants with localized, non-resectable hepatocellular carcinoma utilizing PVA, lipiodol, doxorubicin.
Gastrointestinal disorders Abdominal pain	24.3% 27/111 • Number of events 40 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	26.5% 30/113 • Number of events 40 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
Gastrointestinal disorders Abdominal pain upper	15.3% 17/111 • Number of events 22 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	14.2% 16/113 • Number of events 20 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
Gastrointestinal disorders Ascites	6.3% 7/111 • Number of events 9 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	4.4% 5/113 • Number of events 7 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
Gastrointestinal disorders Constipation	9.9% 11/111 • Number of events 14 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	11.5% 13/113 • Number of events 14 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
Gastrointestinal disorders Diarrhoea	3.6% 4/111 • Number of events 4 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	8.8% 10/113 • Number of events 12 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
Gastrointestinal disorders Nausea	29.7% 33/111 • Number of events 48 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	28.3% 32/113 • Number of events 45 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
Gastrointestinal disorders Vomiting	9.0% 10/111 • Number of events 16 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	10.6% 12/113 • Number of events 16 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
General disorders Catheter site pain	5.4% 6/111 • Number of events 7 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	3.5% 4/113 • Number of events 4 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
General disorders Chills	1.8% 2/111 • Number of events 3 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	5.3% 6/113 • Number of events 7 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
General disorders Fatigue	20.7% 23/111 • Number of events 26 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	21.2% 24/113 • Number of events 25 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
General disorders Oedema peripheral	3.6% 4/111 • Number of events 5 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	6.2% 7/113 • Number of events 7 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
General disorders Pyrexia	18.9% 21/111 • Number of events 32 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	16.8% 19/113 • Number of events 20 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
Injury, poisoning and procedural complications Post embolisation syndrome	18.9% 21/111 • Number of events 39 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	18.6% 21/113 • Number of events 38 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
Investigations Alanine aminotransferase increased	10.8% 12/111 • Number of events 16 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	8.0% 9/113 • Number of events 11 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
Investigations Alpha 1 foetoprotein increased	6.3% 7/111 • Number of events 7 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	0.88% 1/113 • Number of events 1 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
Investigations Aspartate aminotransferase increased	10.8% 12/111 • Number of events 15 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	8.8% 10/113 • Number of events 14 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
Investigations Blood alkaline phosphatase increased	7.2% 8/111 • Number of events 10 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	3.5% 4/113 • Number of events 6 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
Investigations Blood bilirubin increased	7.2% 8/111 • Number of events 8 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	3.5% 4/113 • Number of events 4 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
Investigations Weight decreased	8.1% 9/111 • Number of events 10 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	8.0% 9/113 • Number of events 9 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
Metabolism and nutrition disorders Decreased appetite	5.4% 6/111 • Number of events 8 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	15.0% 17/113 • Number of events 18 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
Musculoskeletal and connective tissue disorders Back pain	4.5% 5/111 • Number of events 6 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	7.1% 8/113 • Number of events 8 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
Nervous system disorders Headache	5.4% 6/111 • Number of events 6 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	2.7% 3/113 • Number of events 3 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
Psychiatric disorders Insomnia	5.4% 6/111 • Number of events 6 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	2.7% 3/113 • Number of events 3 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.7% 3/111 • Number of events 4 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	5.3% 6/113 • Number of events 6 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.
Skin and subcutaneous tissue disorders Alopecia	0.90% 1/111 • Number of events 1 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.	19.5% 22/113 • Number of events 22 • All adverse events (AEs) occurring between the date of randomization until study termination, an average of 25.8 and 28.0 months per participant in the hqTACE and cTACE arms respectively.