Phase 3 Study of ThermoDox With Radiofrequency Ablation (RFA) in Treatment of Hepatocellular Carcinoma (HCC)

• Sponsor: Celsion (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00617981
• Collaborator: (none)
• Enrollment: 701
• Locations: 79
• Arms: 2
• Actual Duration (Months): 99
• Patients Per Site: 8.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether ThermoDox, a thermally sensitive liposomal doxorubicin, is effective in the treatment of non-resectable hepatocellular carcinoma when used in conjunction with radiofrequency ablation (RFA).

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: ThermoDox; Drug: 5% Dextrose Solution	Phase 3

Detailed Description

This will be a Phase III, randomized, double-blinded, dummy-controlled, efficacy, and safety study of ThermoDox plus RFA versus RFA plus dummy infusion.

The 50 mg/m2 ThermoDox or dummy infusion will be administered IV over 30 minutes. As part of blinded pre-medication ThermoDox treated subjects will receive 20 mg of dexamethasone orally 48 hours prior to the drug infusion for infusion reaction prophylaxis. Subjects on the control arm will receive a matching dummy pre-medication pill orally at 48 hours prior to infusion of the study treatment. Thirty minutes prior to receiving the ThermoDox infusion, subjects will receive a blinded dose of 20 mg of IV dexamethasone, 50 mg IV diphenhydramine and either 50 mg of IV ranitidine or 20 mg of IV famotidine. Subjects on the control arm will receive a masked dummy pre-medication pill orally at 48 hours prior to infusion of the study medication, and a dummy infusion 30 minutes prior to dummy infusion of D5W (250 cc of 5% Dextrose solution). RFA will be initiated approximately at a minimum of 15 minutes after the initiation of study drug infusion and should be completed no later than 3 hours after study drug infusion initiation. The total length of the RFA procedure is proportional to the size of the tumor(s) involved and is anticipated to range from 12 to 60 minutes for each lesion with an estimated overall procedure time of less than 3 hours.

Subjects with incomplete ablations will be re-treated to complete the ablation according to the treatment assigned at randomization. The completion of an ablation in this manner will restart the timeline of the study-related visits/procedures. This repeated ablation procedure cannot occur earlier than 21 days post-ablation but no later than 14 days after the first post-ablation CT scan assessment. These subjects will start over at screening (see Table 1). If a complete ablation is not achieved after these two study treatments, the subject will be considered a treatment failure and the patient will be discontinued and followed for survival only.

Subjects who recur with local and/or distant intrahepatic HCC after a complete initial ablation will have met the primary endpoint of progression-free survival. However, if these subjects have lesions that are amenable to RFA the standard of care is to consider them for repeat RFA. Therefore, these subjects may receive treatment to which they were randomized if they continue to meet the inclusion and exclusion criteria of the protocol. Subjects who develop any extrahepatic lesion will have met the primary endpoint and will be discontinued from study treatment but will still be followed for overall survival.

Dynamic Contrast CT imaging will be used to assess the effectiveness of the ablation therapy. The blind will be maintained at the level of CT scan reads. All protocol-specified CT images will be centrally read and assessed by the endpoint committee in a blinded fashion. Posttreatment CT scans will be obtained at months 1, 3, 5, 7, 9 and 12 and every three months thereafter until withdrawal. Adverse event assessments and laboratory examinations will occur at each visit. All subjects will be monitored throughout the investigational period.

Patients that meet inclusion/exclusion criteria may be at risk for contrast-induced nephropathy (CIN) when undergoing the required CT with contrast procedures. The investigators must be mindful of the risk factors (e.g. diabetes, borderline renal function) associated with CIN and employ strategies to reduce the risk of CIN. In subjects with diabetes or borderline renal function (creatinine greater than 1.5 mg/dL) special precautions (e.g. hydration, contrast dose reduction, follow up creatinine determination) should be employed. An accepted procedure is adequate intravenous volume expansion with isotonic saline (1.0 - 1.5 mL/kg per hour) for 3-12 hours before the procedure and continued for 6-24 hours.

All randomized subjects will be followed for safety and overall survival.

Study Design

• Study Type: Interventional
• Actual Enrollment: 701 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III, Randomized, Double-Blinded, Dummy-Controlled Study of the Efficacy and Safety of ThermoDox® (Thermally Sensitive Liposomal Doxorubicin) in Combination With Radiofrequency Ablation (RFA) Compared to RFA-Alone in the Treatment of Non-Resectable Hepatocellular Carcinoma
• Actual Study Start Date: May 1, 2008
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 ThermoDox 50 mg/m2 start infusion over 30 minutes about 15 minutes before radiofrequency ablation begins.	Drug: ThermoDox; Thermally Sensitive Liposomal Doxorubicin 50 mg/m2 Single 30 minute intravenous infusion
Sham Comparator: 2 Sham infusion over 30 minutes about 15 minutes before radiofrequency ablation begins.	Drug: 5% Dextrose Solution; Single 30 minute intravenous infusion

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival Will be Measured From the Date of Randomization to the First Date on Which One of the Following Occurs. o Local Recurrence o Any New Distant Intrahepatic HCC Tumor o Any New Extrahepatic HCC Tumor o Death From Any Cause [3 years]

Secondary Outcome Measures

1. Overall Survival as Measured by Time From Randomization to Death or the End of the Study. [3 years]

2. Time to Definite Worsening as Per Patient-Reported Outcomes [3 years]

3. Time to Local Recurrence. [3 years]

4. Safety [3 years]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosed hepatocellular carcinoma (HCC)

• No more than 4 HCC lesions with at least one ≥ 3.0 cm and none > 7.0 cm in maximum diameter, based on diagnosis at screening.

• If a subject has a large lesion (5.0 - 7.0 cm), any other lesions must be less than 5.0 cm.

• Anticipated ablation volume will be no larger than either removal of 3 hepatic segments or removal of more than 30% of total liver volume (as per maximum surgical limit).

• If additional lesions are discovered during the laparoscopic or open treatment procedure, that were undetectable by CT at screening, the size and location of the lesion(s) will be recorded in the CRF and the lesions will be treated at the discretion of the physician and guided by the local standard of care. The subject will remain on study if all lesions are treated. If any lesions cannot be completely ablated within two treatment attempts the subject will be considered a treatment failure.

• Study subjects being considered for re-treatment after disease progression may have more than 4 lesions.

• Male or female 18 years of age or older.

• Are willing to sign an informed consent form, indicating that they are aware of the investigational nature of this study that is in keeping with the policies of the institution.

• Be an appropriate candidate for receiving RFA as a medically indicated treatment as evaluated by the following factors:

• Number of lesions

• Size of lesions

• Overall health of liver

• Not a candidate for surgical resection

• Have an echocardiogram revealing a Left Ventricular Ejection Fraction (LVEF) ≥ 50%. Measurements with a multiple gated acquisition (MUGA) scan are allowed if an echocardiogram cannot be performed. The same method of measurement should be used to evaluate ejection fraction (EF) of the subject for the duration of the study.

• Willing to return to the study site for their study visits.

• Have life expectancy of ≥ 4 months.

• Have Child-Pugh Class A or B liver disease without encephalopathy or/and ascites.

Exclusion Criteria:

• Have serious medical illnesses including, but not limited to, congestive heart failure, myocardial infarction or cerebral vascular accident within the last six months, or life threatening cardiac arrhythmias.

• Is scheduled for liver transplantation.

• Have previously received any treatment for HCC (except for study subjects being considered for completion of treatment or re-treatment).

• Have previously received any doxorubicin (study subjects being considered for completion of treatment or re-treatment may have received ThermoDox previously).

• Have extrahepatic metastasis.

• Are pregnant or breast-feeding. In women of childbearing potential, a negative pregnancy test (serum) is required prior to study treatment.

• Women of childbearing potential who are not practicing an acceptable form of birth control (i.e. diaphragm, cervical cap, condom, surgical sterility or birth control pills. Women whose partner has undergone a vasectomy must use a second form of birth control).

• Have any known allergic reactions to any of the drugs or liposomal components or intravenous imaging agents to be used in this study.

• Have portal or hepatic vein tumor invasion/thrombosis.

• Have INR > 1.5 times the institution's upper normal limit (UNL), except in subjects who are therapeutically anticoagulated for medical conditions unrelated to HCC such as atrial fibrillation. Subjects may be re-screened after condition is treated or anticoagulant is withheld.

• Have platelet count < 75,000/mm3, absolute neutrophil count < 1500/mm3, or Hgb < 10.0 g/dL (unless the hemoglobin value has been stable, the subject is cardiovascularly stable, asymptomatic and judged able to withstand the RFA procedure).

• Have serum creatinine ≥ 2.5 mg/dL or calculated creatinine clearance (CrCl) ≤ 25.0 mL/min.

• Have serum bilirubin > 3.0 mg/dL.

• Have serum albumin < 2.8 g/dL.

• Have body temperature >1010F (38.30C) immediately prior to study treatment.

• Have contraindications to receiving doxorubicin HCl.

• Are being treated with other investigational agents.

• Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication (study subjects being considered for completion of treatment or re-treatment may have received ThermoDox previously).

• Have other concurrent malignancy (subjects with treated squamous cell carcinoma of the skin or basal cell carcinoma of the skin may be included), evidence of extrahepatic cancer from their primary malignancy, or ongoing, medically significant active infection.

• Documented HIV positive.

• NYHA class III or IV functional classification for heart failure.

• Evidence of hemachromatosis.

• Have history of contrast-induced nephropathy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA	Los Angeles	California	United States	90095
2	Mayo Clinic - Jacksonville, Florida	Jacksonville	Florida	United States	32224
3	University Of Louisville	Louisville	Kentucky	United States	40202
4	Mayo Clinic	Rochester	Minnesota	United States	55905
5	Mount Sinai School of Medicine	New York	New York	United States	10029
6	Cleveland Clinic	Cleveland	Ohio	United States	44195
7	Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
8	Geisinger Health System	Wilkes Barre	Pennsylvania	United States	18711
9	University of Texas Health Science Center	San Antonio	Texas	United States	78229
10	Vancouver General Hospital	Vancouver	British Columbia	Canada
11	Toronto General Hospital	Toronto	Ontario	Canada	M5G 2L4
12	The 1st Affiliated Hospital, Fujian Medical University	Fuzhou	Fujian	China	350005
13	Tongji Hospital	Wuhan	Hubei	China	430030
14	Nanjing Drum Tower Hospital, The Affilitated Hospital of Nanjing University Medical School	Nanjing	Jiangsu	China	210008
15	The First Affiliated Hospital of Suzhou University	Suzhou	Jiangsu	China	215006
16	The First Hospital of Jilin University	Changchun	Jilin	China	130021
17	Tianjin Cancer Hospital	Tianjin	Tianjin	China	300060
18	The First Affiliated Hospital of Zhejiang University	Hangzhou	Zhejiang	China	310013
19	Cancer Institute and Hospital, Chinese Academy of Medical Sciences	Beijing		China	100021
20	Beijing Cancer Hospital, Peking University School of Oncology	Beijing		China	100036
21	Beijing You An Hospital, Capital Medical University	Beijing		China	100069
22	Beijing You An Hospital，Capital Medical University	Beijing		China	100069
23	Southwest Hospital, The First Affiliated Hospital of the Third Military Medical University	Chongqing		China	400038
24	Sun Yat-Sen University Cancer Center	Guangzhou		China	510060
25	Oncology Center of Nanfang Hospital, Southern Medical University	Guangzhou		China	510515
26	Shanghai Changhai Hospital, Second Military Medical University	Shanghai		China	200433
27	Tianjin No. 3 Central Hospital	Tianjin		China	300170
28	Queen Mary Hospital	Hong Kong		Hong Kong
29	Azienda Ospedaliera di Padova	Padova	Veneto	Italy	35128
30	Azienda Ospedaliero-Universitaria di Bologna Policlinico S.Orsola Malpighi	Bologna		Italy	40138
31	Ospedale Classificato San Giuseppe, Milano	Milano		Italy	20123
32	Azienda Ospedaliera San Gerardo	Monza		Italy	20052
33	Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Pascale" di Napoli	Napoli		Italy	80131
34	Azienda Ospedaliero-Univeristaria Pisana	Pisa		Italy	56124
35	Istituto dei Tumori Regina Elena	Roma		Italy	00144
36	Azienda Sanitaria Ospedaliera Ordine Mauriziano di Torino Presidio Ospedaliero "Umberto I"	Torino		Italy	10128
37	Chiba University Hospital	Chiba		Japan	260-8677
38	Iwate Medical University Hospital	Iwate		Japan	020-8505
39	Yamanashi Prefectural Central Hospital	Koufu City		Japan	400-8506
40	Mie University Hospital	Mie		Japan	514-8507
41	Saiseikai Niigata Daini Hospital	Niigata City		Japan	950-1104
42	Okayama University Hospital	Okayama City		Japan	700-8558
43	Kyoundo Hospital	Tokyo		Japan	101-0062
44	The University of Tokyo Hospital	Tokyo		Japan	113-8655
45	Japanese Red Cross Medical Center	Tokyo		Japan	150-8935
46	JR Tokyo General Hospital	Tokyo		Japan	151-8528
47	Kanto Central Hospital	Tokyo		Japan	158-8531
48	Wakayama Medical University	Wakayama		Japan	641-8510
49	Yokohama City University Medical Center	Yokohama City		Japan	232-0024
50	Soonchunhyang University Bucheon Hospital	Gyeonggi-do	Bucheon-si	Korea, Republic of
51	Samsung Medical Center	Seoul	Gangnam-gu	Korea, Republic of	135-710
52	Inje University Ilsan Paik Hospital	Gyeonggi-do	Goyang-si	Korea, Republic of	411-706
53	Kyungpook National University Hospital	Daegu	Gyeongsangbuk-do	Korea, Republic of	700-721
54	Seoul National University Hospital	Seoul	Jongno-gu	Korea, Republic of	110-744
55	Kyungpook National University Hospital	Daegu	Jung-gu	Korea, Republic of	700-721
56	The Catholic University of Korea, Kangnam St.Mary's Hospital	Seoul	Seocho-gu	Korea, Republic of	137-701
57	Pusan National University Hospital	Busan		Korea, Republic of	602-739
58	Seoul National University Bundang Hospital	Gyunggido		Korea, Republic of	464-707
59	Yonsei University Severance Hospital	Seoul		Korea, Republic of	120-752
60	Korea University Medical Center Anam Hospital	Seoul		Korea, Republic of	136-705
61	Asan Medical Center	Seoul		Korea, Republic of	138-736
62	University Malaya Medical Centre	Kuala Lumpur		Malaysia	59100
63	The Medical City	Pasig City, Metro Manila		Philippines	1605
64	St. Luke's Medical Center	Quezon City		Philippines	1112
65	Cardinal Santos Medical Center	San Juan City		Philippines	1053
66	Chinese General Hospital and Medical Center	Sta Cruz, Manila		Philippines	1003
67	Chang-Gung Memorial Hospital - Chiayi Branch	Putzu City	Chiayi	Taiwan	613
68	Chang Gung Memorial Hospital - Kao Shiung	KaoShiung	Kaohsiung County	Taiwan	833
69	Chang Gung Memorial Hospital - Linkou	Linkou	Taoyuan	Taiwan	333
70	Chang Gung Memorial Hospital - Keelung	Keelung		Taiwan	204
71	China Medical University Hospital	Taichung		Taiwan	404
72	Taichung Veterans General Hospital	Taichung		Taiwan	407
73	National Taiwan University Hospital	Taipei		Taiwan	100
74	Taipei Veterans General Hospital	Taipei		Taiwan	112
75	Tri-Service General Hospital	Taipei		Taiwan	114
76	Songklanagarind Hospital	Hat Yai	Songkla	Thailand	90110
77	King Chulalongkorn Memorial Hospital	Bangkok		Thailand	10330
78	Siriraj Hospital	Bangkok		Thailand	10700
79	Thammasat University Hospital	Pathumthani		Thailand	12120

Sponsors and Collaborators

• Celsion

Investigators

• Study Director: Ronnie T Poon, M.D., Queen Mary Hospital, University of Hong Kong
• Study Director: Riccardo Lencioni, M.D., University of Pisa

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Celsion
• ClinicalTrials.gov Identifier: NCT00617981
• Other Study ID Numbers: 104-06-301
• First Posted: Feb 18, 2008
• Last Update Posted: Apr 25, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Celsion: hepatocellular carcinoma; liver cancer
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular

Study Results

Participant Flow

Arm/Group Title	ThermoDox + RFA	Sham + RFA
Arm/Group Description	ThermoDox should be administered at 50 mg/m2. The infusion should start approximately 15 minutes before radiofrequency ablation begins and continue for approximately 30 minutes. ThermoDox: Thermally Sensitive Liposomal Doxorubicin 50 mg/m2 Single 30 minute intravenous infusion	Sham infusion should start approximately 15 minutes before radiofrequency ablation begins and continue for approximately 30 minutes. 5% Dextrose Solution: Single 30 minute intravenous infusion
Period Title: Overall Study
STARTED	354	347
COMPLETED	244	245
NOT COMPLETED	110	102

Baseline Characteristics

Arm/Group Title	ThermoDox + RFA	Sham + RFA	Total
Arm/Group Description	ThermoDox 50 mg/m2 start infusion over 30 minutes about 15 minutes before radiofrequency ablation begins. ThermoDox: Thermally Sensitive Liposomal Doxorubicin 50 mg/m2 Single 30 minute intravenous infusion	Sham infusion over 30 minutes about 15 minutes before radiofrequency ablation begins. 5% Dextrose Solution: Single 30 minute intravenous infusion	Total of all reporting groups
Overall Participants	354	347	701
Age, Customized (participants) [Number]
<40	7 2%	10 2.9%	17 2.4%
40-<45	13 3.7%	14 4%	27 3.9%
45-<50	18 5.1%	25 7.2%	43 6.1%
50-<55	42 11.9%	44 12.7%	86 12.3%
55-<60	57 16.1%	50 14.4%	107 15.3%
60-<65	65 18.4%	64 18.4%	129 18.4%
65-<70	44 12.4%	45 13%	89 12.7%
70-<75	51 14.4%	42 12.1%	93 13.3%
75-<80	33 9.3%	34 9.8%	67 9.6%
80-<85	19 5.4%	13 3.7%	32 4.6%
85+	2 0.6%	4 1.2%	6 0.9%
Missing	3 0.8%	2 0.6%	5 0.7%
Sex: Female, Male (Count of Participants)
Female	87 24.6%	84 24.2%	171 24.4%
Male	267 75.4%	263 75.8%	530 75.6%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	42 11.9%	26 7.5%	68 9.7%
Japanese	8 2.3%	11 3.2%	19 2.7%
Korean	83 23.4%	91 26.2%	174 24.8%
Taiwanese	66 18.6%	62 17.9%	128 18.3%
Chinese	115 32.5%	125 36%	240 34.2%
Other	40 11.3%	32 9.2%	72 10.3%
Region of Enrollment (participants) [Number]
United States	10 2.8%	5 1.4%	15 2.1%
Philippines	18 5.1%	21 6.1%	39 5.6%
Taiwan	68 19.2%	63 18.2%	131 18.7%
Hong Kong	6 1.7%	9 2.6%	15 2.1%
Canada	5 1.4%	10 2.9%	15 2.1%
Thailand	16 4.5%	8 2.3%	24 3.4%
Malaysia	7 2%	6 1.7%	13 1.9%
Japan	8 2.3%	10 2.9%	18 2.6%
Italy	32 9%	17 4.9%	49 7%
China	104 29.4%	104 30%	208 29.7%
Korea, Republic of	82 23.2%	92 26.5%	174 24.8%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival Will be Measured From the Date of Randomization to the First Date on Which One of the Following Occurs. o Local Recurrence o Any New Distant Intrahepatic HCC Tumor o Any New Extrahepatic HCC Tumor o Death From Any Cause
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ThermoDox + RFA	Sham + RFA
Arm/Group Description	ThermoDox 50 mg/m2 start infusion over 30 minutes about 15 minutes before radiofrequency ablation begins. ThermoDox: Thermally Sensitive Liposomal Doxorubicin 50 mg/m2 Single 30 minute intravenous infusion	Sham infusion over 30 minutes about 15 minutes before radiofrequency ablation begins. 5% Dextrose Solution: Single 30 minute intravenous infusion
Measure Participants	354	347
Number (95% Confidence Interval) [Time to Progression (months)]	13.97	13.87

2. Secondary Outcome

Title	Overall Survival as Measured by Time From Randomization to Death or the End of the Study.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Time to Definite Worsening as Per Patient-Reported Outcomes
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Time to Local Recurrence.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Safety
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	ThermoDox + RFA		Sham + RFA
Arm/Group Description	ThermoDox 50 mg/m2 start infusion over 30 minutes about 15 minutes before radiofrequency ablation begins. ThermoDox: Thermally Sensitive Liposomal Doxorubicin 50 mg/m2 Single 30 minute intravenous infusion		Sham infusion over 30 minutes about 15 minutes before radiofrequency ablation begins. 5% Dextrose Solution: Single 30 minute intravenous infusion
All Cause Mortality
	ThermoDox + RFA		Sham + RFA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	ThermoDox + RFA		Sham + RFA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	118/343 (34.4%)		37/334 (11.1%)
Blood and lymphatic system disorders
Neutropenia	56/343 (16.3%)		0/334 (0%)
Leukopenia	19/343 (5.5%)		0/334 (0%)
Febrile Neutropenia	9/343 (2.6%)		0/334 (0%)
Pancytopenia	3/343 (0.9%)		0/334 (0%)
Anaemia	1/343 (0.3%)		1/334 (0.3%)
Bone Marrow Failure	1/343 (0.3%)		0/334 (0%)
Cardiac disorders
Myocardial Infarction	2/343 (0.6%)		0/334 (0%)
Cardiac Failure	0/343 (0%)		1/334 (0.3%)
Cardio-respiratory arrest	0/343 (0%)		1/334 (0.3%)
Myocardial Rupture	0/343 (0%)		1/334 (0.3%)
Pericardial Effusion	0/343 (0%)		1/334 (0.3%)
Gastrointestinal disorders
Abdominal Pain Upper	2/343 (0.6%)		2/334 (0.6%)
Upper Gastrointestinal Haemorrhage	1/343 (0.3%)		3/334 (0.9%)
Oesophageal Varices Haemorrhage	1/343 (0.3%)		2/334 (0.6%)
Ascites	2/343 (0.6%)		0/334 (0%)
Diarrhoea	2/343 (0.6%)		0/334 (0%)
Ileus	0/343 (0%)		2/334 (0.6%)
Abdominal Pain	1/343 (0.3%)		0/334 (0%)
Duodenal Ulcer	1/343 (0.3%)		0/334 (0%)
Gastric Ulcer Haemorrhage	1/343 (0.3%)		0/334 (0%)
Gastric Varices Haemorrhage	1/343 (0.3%)		0/334 (0%)
Gastritis	0/343 (0%)		1/334 (0.3%)
Gastrointestinal Haemorrhage	1/343 (0.3%)		0/334 (0%)
Gastrooesophageal Reflux Disease	1/343 (0.3%)		0/334 (0%)
Large Intestine Perforation	1/343 (0.3%)		0/334 (0%)
Localised Intraabdominal Fluid Collection	0/343 (0%)		1/334 (0.3%)
Mesenteric Vein Thrombosis	1/343 (0.3%)		0/334 (0%)
Nausea	1/343 (0.3%)		0/334 (0%)
Peritoneal Haemorrhage	1/343 (0.3%)		0/334 (0%)
Portal Hypertensive Gastropathy	0/343 (0%)		1/334 (0.3%)
Stress Ulcer	0/343 (0%)		1/334 (0.3%)
General disorders
Pyrexia	1/343 (0.3%)		2/334 (0.6%)
Multi-organ Failure	0/343 (0%)		2/334 (0.6%)
Asthenia	0/343 (0%)		1/334 (0.3%)
Hyperpyrexia	1/343 (0.3%)		0/334 (0%)
Oedema Peripheral	1/343 (0.3%)		0/334 (0%)
Hepatobiliary disorders
Hepatic Function Abnormal	2/343 (0.6%)		1/334 (0.3%)
Jaundice Cholestatic	0/343 (0%)		2/334 (0.6%)
Bile Duct Stone	0/343 (0%)		1/334 (0.3%)
Hepatic Failure	0/343 (0%)		1/334 (0.3%)
Hyperbilirubinaemia	1/343 (0.3%)		0/334 (0%)
Jaundice	1/343 (0.3%)		0/334 (0%)
Liver Disorder	1/343 (0.3%)		0/334 (0%)
Liver Injury	0/343 (0%)		1/334 (0.3%)
Infections and infestations
Pneumonia	1/343 (0.3%)		2/334 (0.6%)
Cellulitis	2/343 (0.6%)		0/334 (0%)
Liver Abscess	2/343 (0.6%)		0/334 (0%)
Neutropenic Sepsis	2/343 (0.6%)		0/334 (0%)
Peritonitis Bacterial	2/343 (0.6%)		0/334 (0%)
Sepsis	1/343 (0.3%)		1/334 (0.3%)
Septic Shock	1/343 (0.3%)		1/334 (0.3%)
Abdominal Infection	0/343 (0%)		1/334 (0.3%)
Anal Abscess	1/343 (0.3%)		0/334 (0%)
Bacteraemia	0/343 (0%)		1/334 (0.3%)
Furuncle	1/343 (0.3%)		0/334 (0%)
Gastritis Viral	1/343 (0.3%)		0/334 (0%)
Infected Cyst	0/343 (0%)		1/334 (0.3%)
Infection	1/343 (0.3%)		0/334 (0%)
Salmonella Sepsis	1/343 (0.3%)		0/334 (0%)
Wound Infection Staphylococcal	0/343 (0%)		1/334 (0.3%)
Injury, poisoning and procedural complications
Hepatic Rupture	3/343 (0.9%)		0/334 (0%)
Post Procedural Complication	1/343 (0.3%)		2/334 (0.6%)
Post Procedural Haemorrhage	2/343 (0.6%)		1/334 (0.3%)
Procedural Pain	1/343 (0.3%)		1/334 (0.3%)
Wound Complication	1/343 (0.3%)		1/334 (0.3%)
Biloma	0/343 (0%)		1/334 (0.3%)
Fall	0/343 (0%)		1/334 (0.3%)
Hepatic Function Abnormal	1/343 (0.3%)		0/334 (0%)
Hypotension	0/343 (0%)		1/334 (0.3%)
Puncture Site Haemorrhage	0/343 (0%)		1/334 (0.3%)
Skin laceration	1/343 (0.3%)		0/334 (0%)
Wound Haemorrhage	1/343 (0.3%)		0/334 (0%)
Investigations
Neutrophil Count Decreased	9/343 (2.6%)		0/334 (0%)
Alanine Aminotransferase Increased	1/343 (0.3%)		0/334 (0%)
Aspartate Aminotransferase Increased	1/343 (0.3%)		0/334 (0%)
Blood Bilirubin Increased	1/343 (0.3%)		0/334 (0%)
Haemoglobin Decreased	1/343 (0.3%)		0/334 (0%)
Platelet Count Decreased	1/343 (0.3%)		0/334 (0%)
White Blood Cell Count Decreased	1/343 (0.3%)		0/334 (0%)
Metabolism and nutrition disorders
Diabetes Mellitus Inadequate Control	2/343 (0.6%)		0/334 (0%)
Decreased Appetite	0/343 (0%)		1/334 (0.3%)
Hypocalcaemia	0/343 (0%)		1/334 (0.3%)
Hypoglycaemia	0/343 (0%)		1/334 (0.3%)
Hyponatraemia	1/343 (0.3%)		0/334 (0%)
Metabolic Acidosis	1/343 (0.3%)		0/334 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain	0/343 (0%)		1/334 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour Thrombosis	1/343 (0.3%)		0/334 (0%)
Nervous system disorders
Hepatic encephalopthy	1/343 (0.3%)		1/334 (0.3%)
Cerebral Ischaemia	0/343 (0%)		1/334 (0.3%)
Convulsion	1/343 (0.3%)		0/334 (0%)
Depressed Level of Consciousness	1/343 (0.3%)		0/334 (0%)
Haemorrhagic Stroke	1/343 (0.3%)		0/334 (0%)
Transient Ischaemic Attack	0/343 (0%)		1/334 (0.3%)
Psychiatric disorders
Delirium Tremens	1/343 (0.3%)		0/334 (0%)
Mood Altered	1/343 (0.3%)		0/334 (0%)
Renal and urinary disorders
Acute Prerenal Failure	1/343 (0.3%)		0/334 (0%)
Renal Failure Acute	1/343 (0.3%)		0/334 (0%)
Urethral Stenosis	1/343 (0.3%)		0/334 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	2/343 (0.6%)		1/334 (0.3%)
Aspiration	0/343 (0%)		1/334 (0.3%)
Chronic Obstructive Pulmonary Disease	0/343 (0%)		1/334 (0.3%)
Haemothorax	1/343 (0.3%)		0/334 (0%)
Respiratory Failure	1/343 (0.3%)		0/334 (0%)
Surgical and medical procedures
Biliary Drainage	0/343 (0%)		1/334 (0.3%)
Vascular disorders
Hypotension	1/343 (0.3%)		0/334 (0%)
Shock Haemorrhagic	0/343 (0%)		1/334 (0.3%)
Other (Not Including Serious) Adverse Events
	ThermoDox + RFA		Sham + RFA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	327/343 (95.3%)		301/334 (90.1%)
Blood and lymphatic system disorders
Neutropenia	87/343 (25.4%)		6/334 (1.8%)
Leukopenia	73/343 (21.3%)		5/334 (1.5%)
Thrombocytopenia	18/343 (5.2%)		2/334 (0.6%)
Gastrointestinal disorders
Abdominal Pain	50/343 (14.6%)		62/334 (18.6%)
Nausea	53/343 (15.5%)		43/334 (12.9%)
Abdominal Pain Upper	44/343 (12.8%)		44/334 (13.2%)
Vomiting	35/343 (10.2%)		28/334 (8.4%)
Constipation	21/343 (6.1%)		15/334 (4.5%)
Abdominal Distension	15/343 (4.4%)		17/334 (5.1%)
General disorders
Pyrexia	56/343 (16.3%)		98/334 (29.3%)
Fatigue	20/343 (5.8%)		14/334 (4.2%)
Injury, poisoning and procedural complications
Procedural Pain	28/343 (8.2%)		39/334 (11.7%)
Wound Complication	33/343 (9.6%)		33/334 (9.9%)
Investigations
Aspartate Aminotransferase Increased	70/343 (20.4%)		70/334 (21%)
Alanine Aminotransferase Increased	61/343 (17.8%)		62/334 (18.6%)
Blood Bilirubin Increased	29/343 (8.5%)		39/334 (11.7%)
White Blood Cell Count Decreased	48/343 (14%)		12/334 (3.6%)
Neutrophil Count Decreased	38/343 (11.1%)		9/334 (2.7%)
Platelet Count Decreased	20/343 (5.8%)		20/334 (6%)
Blood Lactate Dehydrogenase Increased	19/343 (5.5%)		17/334 (5.1%)
Neutrophil Count Increased	24/343 (7%)		8/334 (2.4%)
White Blood Cell Count Increased	24/343 (7%)		5/334 (1.5%)
Metabolism and nutrition disorders
Decreased Appetite	32/343 (9.3%)		13/334 (3.9%)
Renal and urinary disorders
Haematuria	13/343 (3.8%)		23/334 (6.9%)
Respiratory, thoracic and mediastinal disorders
Cough	26/343 (7.6%)		49/334 (14.7%)
Skin and subcutaneous tissue disorders
Alopecia	173/343 (50.4%)		2/334 (0.6%)
Vascular disorders
Hypertension	18/343 (5.2%)		17/334 (5.1%)

Limitations/Caveats

[Not Specified]

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.