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

• Sponsor: Merit Medical Systems, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01387932
• Collaborator: (none)
• Enrollment: 235
• Locations: 23
• Arms: 2
• Actual Duration (Months): 116.1
• Patients Per Site: 10.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Device: HepaSphere/QuadraSphere Microspheres; Procedure: PVA, lipiodol, doxorubicin	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 235 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.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.
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: Participants are blinded to the treatment they are randomized to (cTACE or hqTACE). Central Reviewers (two interventional radiologists) will evaluate study participant's liver MRIs to assess the tumor response. The Central Reviewers will be blinded to the treatment the participant received.
• Primary Purpose: Treatment
• Official Title: Phase 3 Prospective, Randomized, Blinded, and Controlled Investigation of HepaSphere/QuadraSphere Microspheres for Delivery of Doxorubicin for the Treatment of Hepatocellular Carcinoma
• Actual Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Feb 1, 2021
• Actual Study Completion Date: Feb 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HepaSphere/QuadraSphere TACE HepaSphere/QuadraSphere TACE	Device: HepaSphere/QuadraSphere Microspheres; HepaSphere/QuadraSphere Microspheres loaded with doxorubicin
Active Comparator: Conventional TACE Conventional TACE	Procedure: PVA, lipiodol, doxorubicin; Conventional TACE procedure using PVA, lipiodol and doxorubicin

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

Other Outcome Measures

1. Number of TACE-Related Adverse Events in Subjects Treated With HepaSphere/QuadraSphere vs Subjects Treated With Conventional TACE. [30 days]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

1. 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.

1. 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.

1. 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

1. Patient MUST meet at least ONE of the following criteria:

2. Stage Child-Pugh B 7 ii. Recurrent HCC iii.Performance status ECOG 1

3. Patient has a life expectancy of at least 6 months

4. 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:

1. White Blood Cell count (WBC) <3000 cells/mm₃

1. Absolute Neutrophil <1500 cells/mm₃

2. Cardiac ejection fraction <50%

3. Other condition deemed exclusionary by physician

1. Any contraindication for hepatic embolization, including the following:

2. Porto-systemic shunt, or an arteriovenous shunt that cannot be adequately closed prior to chemoembolization

1. Hepatofugal blood flow

2. Serum creatinine > 2mg/dL

3. 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

1. AST > 5X upper limit of normal for lab

1. ALT > 5X upper limit of normal for lab

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35209
2	Tuscon Medical Center	Tucson	Arizona	United States	85711
3	Greater Arkansas Veterans Healthcare	Little Rock	Arkansas	United States	72205
4	VA Greater Los Angeles Healthcare System	Los Angeles	California	United States	90073
5	UCLA	Los Angeles	California	United States	90095
6	Palo Alto Veterans Institute for Research	Palo Alto	California	United States	94304
7	Stanford University	Stanford	California	United States	94305
8	Georgetown University Hospital	Washington	District of Columbia	United States	20007
9	Tampa General Hospital	Tampa	Florida	United States	33606
10	Northwestern University	Chicago	Illinois	United States	60611
11	Massachusetts General Hospital	Boston	Massachusetts	United States	35209
12	Albany Medical Center	Albany	New York	United States	12208
13	Mount Sinai Medical Center	New York	New York	United States	10029
14	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
15	Albert Einstein Healthcare	Philadelphia	Pennsylvania	United States	19141
16	VA Pittsburgh Healthcare System	Pittsburgh	Pennsylvania	United States	15261
17	MUSC Medical Center (Medical University of South Carolina)	Charleston	South Carolina	United States	29425
18	UT Health and Science Center	San Antonio	Texas	United States	78229
19	University Hospitals K.U. Leuven (Dept of Hematology)	Leuven		Belgium	3000
20	Hospital Saint Andre	Bordeaux		France	33075
21	Hospital Paul Brousse	Villejuif cedex		France	94804
22	Evgenidion University Hospital	Athens		Greece	115 28
23	S. Croce e Carle Hospital	Cuneo		Italy	12100

Sponsors and Collaborators

• 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 Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 21, 2014

More Information

Publications

None provided.

• Responsible Party: Merit Medical Systems, Inc.
• ClinicalTrials.gov Identifier: NCT01387932
• Other Study ID Numbers: HCC-P3-11-01
• First Posted: Jul 6, 2011
• Last Update Posted: Nov 30, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Merit Medical Systems, Inc.: Hepatocellular carcinoma; TACE; HepaSphere Microspheres; QuadraSphere Microspheres; Doxorubicin
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Doxorubicin; Ethiodized Oil

Study Results

Participant Flow

Recruitment Details	Study enrollment began in June 2011 and ended in May 2017.
Pre-assignment Detail	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.

Arm/Group Title	HepaSphere/QuadraSphere TACE	Conventional TACE
Arm/Group Description	HepaSphere/QuadraSphere TACE Transarterial chemoembolization in participants with localized, non-resectable hepatocellular carcinoma utilizing HepaSphere/QuadraSphere Microspheres loaded with doxorubicin.	Conventional TACE Transarterial chemoembolization in participants with localized, non-resectable hepatocellular carcinoma utilizing PVA, lipiodol, doxorubicin.
Period Title: Randomized and Treated
STARTED	118	117
COMPLETED	111	113
NOT COMPLETED	7	4
Period Title: Randomized and Treated
STARTED	111	113
COMPLETED	111	113
NOT COMPLETED	0	0
Period Title: Randomized and Treated
STARTED	111	113
COMPLETED	27	23
NOT COMPLETED	84	90

Baseline Characteristics

Arm/Group Title	HepaSphere/QuadraSphere TACE	Conventional TACE	Total
Arm/Group Description	HepaSphere/QuadraSphere TACE HepaSphere/QuadraSphere Microspheres: HepaSphere/QuadraSphere Microspheres loaded with doxorubicin	Conventional TACE PVA, lipiodol, doxorubicin: Conventional TACE procedure using PVA, lipiodol and doxorubicin	Total of all reporting groups
Overall Participants	118	117	235
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.0 (8.95)	64.2 (8.40)	64.1 (8.66)
Sex: Female, Male (Count of Participants)
Female	24 20.3%	20 17.1%	44 18.7%
Male	94 79.7%	97 82.9%	191 81.3%
Race/Ethnicity, Customized (Count of Participants)
Asian	8 6.8%	6 5.1%	14 6%
Native Hawaiian or Pacific Islander	0 0%	1 0.9%	1 0.4%
Black or African American	8 6.8%	9 7.7%	17 7.2%
White	95 80.5%	96 82.1%	191 81.3%
More than one race	2 1.7%	1 0.9%	3 1.3%
Unknown or Not Reported	5 4.2%	4 3.4%	9 3.8%
Region of Enrollment (Count of Participants)
Greece	25 21.2%	24 20.5%	49 20.9%
Belgium	2 1.7%	2 1.7%	4 1.7%
United States	78 66.1%	79 67.5%	157 66.8%
Italy	4 3.4%	4 3.4%	8 3.4%
France	2 1.7%	4 3.4%	6 2.6%

Outcome Measures

1. Primary Outcome

Title	Median Overall Survival
Description	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.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	HepaSphere/QuadraSphere TACE	Conventional TACE
Arm/Group Description	HepaSphere/QuadraSphere TACE HepaSphere/QuadraSphere Microspheres: HepaSphere/QuadraSphere Microspheres loaded with doxorubicin	Conventional TACE PVA, lipiodol, doxorubicin: Conventional TACE procedure using PVA, lipiodol and doxorubicin
Measure Participants	27	23
Median (95% Confidence Interval) [Months]	9.0	7.0

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Data was not collected.

Arm/Group Title	HepaSphere/QuadraSphere TACE	Conventional TACE
Arm/Group Description	HepaSphere/QuadraSphere TACE Transarterial chemoembolization in participants with localized, non-resectable hepatocellular carcinoma utilizing HepaSphere/QuadraSphere Microspheres loaded with doxorubicin.	Conventional TACE Transarterial chemoembolization in participants with localized, non-resectable hepatocellular carcinoma utilizing PVA, lipiodol, doxorubicin.
Measure Participants	0	0

3. Other Pre-specified Outcome

Title	Number of TACE-Related Adverse Events in Subjects Treated With HepaSphere/QuadraSphere vs Subjects Treated With Conventional TACE.
Description	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.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	HepaSphere/QuadraSphere TACE	Conventional TACE
Arm/Group Description	HepaSphere/QuadraSphere TACE Transarterial chemoembolization in participants with localized, non-resectable hepatocellular carcinoma utilizing HepaSphere/QuadraSphere Microspheres loaded with doxorubicin.	Conventional TACE Transarterial chemoembolization in participants with localized, non-resectable hepatocellular carcinoma utilizing PVA, lipiodol, doxorubicin.
Measure Participants	111	113
Number [A TACE related Adverse Event]	149	164

Adverse Events

Time Frame	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.
Arm/Group Title	HepaSphere/QuadraSphere TACE		Conventional TACE
Arm/Group Description	HepaSphere/QuadraSphere TACE Transarterial chemoembolization in participants with localized, non-resectable hepatocellular carcinoma utilizing HepaSphere/QuadraSphere Microspheres loaded with doxorubicin.		Conventional TACE Transarterial chemoembolization in participants with localized, non-resectable hepatocellular carcinoma utilizing PVA, lipiodol, doxorubicin.
All Cause Mortality
	HepaSphere/QuadraSphere TACE		Conventional TACE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	100/111 (90.1%)		93/113 (82.3%)
Serious Adverse Events
	HepaSphere/QuadraSphere TACE		Conventional TACE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/111 (20.7%)		21/113 (18.6%)
Blood and lymphatic system disorders
Anaemia	1/111 (0.9%)	1	0/113 (0%)	0
Cardiac disorders
Atrial fibrillation	1/111 (0.9%)	2	0/113 (0%)	0
Bradycardia	0/111 (0%)	0	1/113 (0.9%)	1
Cardiac arrest	1/111 (0.9%)	1	1/113 (0.9%)	1
Myocardial infarction	0/111 (0%)	0	1/113 (0.9%)	1
Gastrointestinal disorders
Abdominal pain	2/111 (1.8%)	2	5/113 (4.4%)	6
Abdominal pain upper	0/111 (0%)	0	1/113 (0.9%)	1
Constipation	0/111 (0%)	0	1/113 (0.9%)	1
Diarrhea	1/111 (0.9%)	1	0/113 (0%)	0
Duodenal ulcer hemorrhage	0/111 (0%)	0	1/113 (0.9%)	1
Gastrointestinal hemorrhage	0/111 (0%)	0	1/113 (0.9%)	1
Ileus paralytic	0/111 (0%)	0	1/113 (0.9%)	1
Mesenteric vein thrombosis	0/111 (0%)	0	1/113 (0.9%)	1
Nausea	0/111 (0%)	0	1/113 (0.9%)	1
Oesophageal haemorrhage	0/111 (0%)	0	1/113 (0.9%)	1
Oesophageal varices hemorrhage	1/111 (0.9%)	1	0/113 (0%)	0
Upper gastrointestinal hemorrhage	1/111 (0.9%)	1	0/113 (0%)	0
Varices oesophageal	1/111 (0.9%)	1	0/113 (0%)	0
General disorders
Multi-organ failure	0/111 (0%)	0	2/113 (1.8%)	2
Pain	1/111 (0.9%)	1	0/113 (0%)	0
Pyrexia	1/111 (0.9%)	1	0/113 (0%)	0
Systemic inflammatory response syndrome	0/111 (0%)	0	1/113 (0.9%)	1
Hepatobiliary disorders
Cholecystitis	1/111 (0.9%)	1	0/113 (0%)	0
Cholelithiasis	0/111 (0%)	0	1/113 (0.9%)	1
Hepatic failure	1/111 (0.9%)	1	0/113 (0%)	0
Hepatic infarction	0/111 (0%)	0	1/113 (0.9%)	1
Portal vein thrombosis	0/111 (0%)	0	1/113 (0.9%)	1
Infections and infestations
Bacterial infection	1/111 (0.9%)	1	0/113 (0%)	0
Enterococcal bacteremia	0/111 (0%)	0	1/113 (0.9%)	1
Groin abscess	1/111 (0.9%)	1	0/113 (0%)	0
Lobar pneumonia	1/111 (0.9%)	1	0/113 (0%)	0
Peritonitis bacteria	1/111 (0.9%)	1	0/113 (0%)	0
Pneumonia	1/111 (0.9%)	1	1/113 (0.9%)	1
Sepsis	1/111 (0.9%)	1	0/113 (0%)	0
Septic shock	0/111 (0%)	0	2/113 (1.8%)	2
Urinary tract infection	0/111 (0%)	0	2/113 (1.8%)	2
Injury, poisoning and procedural complications
Fall	0/111 (0%)	0	1/113 (0.9%)	1
Post embolisation syndrome	3/111 (2.7%)	3	1/113 (0.9%)	1
Vascular pseudoaneurysm	0/111 (0%)	0	1/113 (0.9%)	1
Investigations
Blood bilirubin increased	0/111 (0%)	0	1/113 (0.9%)	1
Blood creatinine increased	0/111 (0%)	0	1/113 (0.9%)	1
Blood glucose increased	0/111 (0%)	0	1/113 (0.9%)	1
Body temperature increased	1/111 (0.9%)	1	0/113 (0%)	0
Liver function test abnormal	0/111 (0%)	0	2/113 (1.8%)	4
Metabolism and nutrition disorders
Food intolerance	1/111 (0.9%)	1	0/113 (0%)	0
Hyperglycaemia	1/111 (0.9%)	1	0/113 (0%)	0
Hyperkalaemia	1/111 (0.9%)	1	0/113 (0%)	0
Hypoglycaemia	1/111 (0.9%)	1	0/113 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/111 (0.9%)	1	0/113 (0%)	0
Muscular weakness	1/111 (0.9%)	1	0/113 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	1/111 (0.9%)	1	0/113 (0%)	0
Oesophageal adenocarcinoma	1/111 (0.9%)	1	0/113 (0%)	0
Nervous system disorders
Cerebrovascular accident	1/111 (0.9%)	1	0/113 (0%)	0
Hepatic encephalopathy	0/111 (0%)	0	2/113 (1.8%)	3
Presyncope	1/111 (0.9%)	1	0/113 (0%)	0
Syncope	1/111 (0.9%)	1	0/113 (0%)	0
Psychiatric disorders
Confusional state	1/111 (0.9%)	1	0/113 (0%)	0
Mental status changes	1/111 (0.9%)	3	1/113 (0.9%)	2
Renal and urinary disorders
Renal failure	0/111 (0%)	0	1/113 (0.9%)	1
Renal failure acute	1/111 (0.9%)	1	2/113 (1.8%)	2
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/111 (0.9%)	1	2/113 (1.8%)	2
Dyspnoea	1/111 (0.9%)	1	2/113 (1.8%)	2
Hiccups	0/111 (0%)	0	1/113 (0.9%)	1
Pneumonia aspiration	1/111 (0.9%)	1	0/113 (0%)	0
Pneumonitis	0/111 (0%)	0	1/113 (0.9%)	1
Pulmonary embolism	0/111 (0%)	0	1/113 (0.9%)	1
Respiratory failure	0/111 (0%)	0	1/113 (0.9%)	1
Other (Not Including Serious) Adverse Events
	HepaSphere/QuadraSphere TACE		Conventional TACE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	86/111 (77.5%)		87/113 (77%)
Gastrointestinal disorders
Abdominal pain	27/111 (24.3%)	40	30/113 (26.5%)	40
Abdominal pain upper	17/111 (15.3%)	22	16/113 (14.2%)	20
Ascites	7/111 (6.3%)	9	5/113 (4.4%)	7
Constipation	11/111 (9.9%)	14	13/113 (11.5%)	14
Diarrhoea	4/111 (3.6%)	4	10/113 (8.8%)	12
Nausea	33/111 (29.7%)	48	32/113 (28.3%)	45
Vomiting	10/111 (9%)	16	12/113 (10.6%)	16
General disorders
Catheter site pain	6/111 (5.4%)	7	4/113 (3.5%)	4
Chills	2/111 (1.8%)	3	6/113 (5.3%)	7
Fatigue	23/111 (20.7%)	26	24/113 (21.2%)	25
Oedema peripheral	4/111 (3.6%)	5	7/113 (6.2%)	7
Pyrexia	21/111 (18.9%)	32	19/113 (16.8%)	20
Injury, poisoning and procedural complications
Post embolisation syndrome	21/111 (18.9%)	39	21/113 (18.6%)	38
Investigations
Alanine aminotransferase increased	12/111 (10.8%)	16	9/113 (8%)	11
Alpha 1 foetoprotein increased	7/111 (6.3%)	7	1/113 (0.9%)	1
Aspartate aminotransferase increased	12/111 (10.8%)	15	10/113 (8.8%)	14
Blood alkaline phosphatase increased	8/111 (7.2%)	10	4/113 (3.5%)	6
Blood bilirubin increased	8/111 (7.2%)	8	4/113 (3.5%)	4
Weight decreased	9/111 (8.1%)	10	9/113 (8%)	9
Metabolism and nutrition disorders
Decreased appetite	6/111 (5.4%)	8	17/113 (15%)	18
Musculoskeletal and connective tissue disorders
Back pain	5/111 (4.5%)	6	8/113 (7.1%)	8
Nervous system disorders
Headache	6/111 (5.4%)	6	3/113 (2.7%)	3
Psychiatric disorders
Insomnia	6/111 (5.4%)	6	3/113 (2.7%)	3
Respiratory, thoracic and mediastinal disorders
Dyspnoea	3/111 (2.7%)	4	6/113 (5.3%)	6
Skin and subcutaneous tissue disorders
Alopecia	1/111 (0.9%)	1	22/113 (19.5%)	22

Limitations/Caveats

Study was terminated early due to insufficient enrolment to support analysis of endpoints. A full safety analysis was completed and is reported.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.