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Trial record 1 of 3 for:    Hepatocellular Carcinoma Study of RFA and ThermoDox
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Phase 3 Study of ThermoDox With Radiofrequency Ablation (RFA) in Treatment of Hepatocellular Carcinoma (HCC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00617981
Recruitment Status : Completed
First Posted : February 18, 2008
Results First Posted : March 24, 2017
Last Update Posted : April 25, 2017
Sponsor:
Information provided by (Responsible Party):
Celsion

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Hepatocellular Carcinoma
Interventions Drug: ThermoDox
Drug: 5% Dextrose Solution
Enrollment 701
Recruitment Details  
Pre-assignment Details  
Arm/Group Title ThermoDox + RFA Sham + RFA
Hide 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
Arm/Group Title ThermoDox + RFA Sham + RFA Total
Hide 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 Number of Baseline Participants 354 347 701
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 354 participants 347 participants 701 participants
<40 7 10 17
40-<45 13 14 27
45-<50 18 25 43
50-<55 42 44 86
55-<60 57 50 107
60-<65 65 64 129
65-<70 44 45 89
70-<75 51 42 93
75-<80 33 34 67
80-<85 19 13 32
85+ 2 4 6
Missing 3 2 5
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 354 participants 347 participants 701 participants
Female
87
  24.6%
84
  24.2%
171
  24.4%
Male
267
  75.4%
263
  75.8%
530
  75.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 354 participants 347 participants 701 participants
Caucasian 42 26 68
Japanese 8 11 19
Korean 83 91 174
Taiwanese 66 62 128
Chinese 115 125 240
Other 40 32 72
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 354 participants 347 participants 701 participants
United States 10 5 15
Philippines 18 21 39
Taiwan 68 63 131
Hong Kong 6 9 15
Canada 5 10 15
Thailand 16 8 24
Malaysia 7 6 13
Japan 8 10 18
Italy 32 17 49
China 104 104 208
Korea, Republic of 82 92 174
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
Hide Description [Not Specified]
Time Frame 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ThermoDox + RFA Sham + RFA
Hide 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

Overall Number of Participants Analyzed 354 347
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Time to Progression (months)
13.97
(11.47 to 19.26)
13.87
(11.14 to 16.69)
2.Secondary Outcome
Title Overall Survival as Measured by Time From Randomization to Death or the End of the Study.
Hide Description [Not Specified]
Time Frame 3 years
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Time to Definite Worsening as Per Patient-Reported Outcomes
Hide Description [Not Specified]
Time Frame 3 years
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Time to Local Recurrence.
Hide Description [Not Specified]
Time Frame 3 years
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Safety
Hide Description [Not Specified]
Time Frame 3 years
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title ThermoDox + RFA Sham + RFA
Hide 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 (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
ThermoDox + RFA Sham + RFA
Affected / at Risk (%) Affected / at Risk (%)
Total   118/343 (34.40%)   37/334 (11.08%) 
Blood and lymphatic system disorders     
Neutropenia  56/343 (16.33%)  0/334 (0.00%) 
Leukopenia  19/343 (5.54%)  0/334 (0.00%) 
Febrile Neutropenia  9/343 (2.62%)  0/334 (0.00%) 
Pancytopenia  3/343 (0.87%)  0/334 (0.00%) 
Anaemia  1/343 (0.29%)  1/334 (0.30%) 
Bone Marrow Failure  1/343 (0.29%)  0/334 (0.00%) 
Cardiac disorders     
Myocardial Infarction  2/343 (0.58%)  0/334 (0.00%) 
Cardiac Failure  0/343 (0.00%)  1/334 (0.30%) 
Cardio-respiratory arrest  0/343 (0.00%)  1/334 (0.30%) 
Myocardial Rupture  0/343 (0.00%)  1/334 (0.30%) 
Pericardial Effusion  0/343 (0.00%)  1/334 (0.30%) 
Gastrointestinal disorders     
Abdominal Pain Upper  2/343 (0.58%)  2/334 (0.60%) 
Upper Gastrointestinal Haemorrhage  1/343 (0.29%)  3/334 (0.90%) 
Oesophageal Varices Haemorrhage  1/343 (0.29%)  2/334 (0.60%) 
Ascites  2/343 (0.58%)  0/334 (0.00%) 
Diarrhoea  2/343 (0.58%)  0/334 (0.00%) 
Ileus  0/343 (0.00%)  2/334 (0.60%) 
Abdominal Pain  1/343 (0.29%)  0/334 (0.00%) 
Duodenal Ulcer  1/343 (0.29%)  0/334 (0.00%) 
Gastric Ulcer Haemorrhage  1/343 (0.29%)  0/334 (0.00%) 
Gastric Varices Haemorrhage  1/343 (0.29%)  0/334 (0.00%) 
Gastritis  0/343 (0.00%)  1/334 (0.30%) 
Gastrointestinal Haemorrhage  1/343 (0.29%)  0/334 (0.00%) 
Gastrooesophageal Reflux Disease  1/343 (0.29%)  0/334 (0.00%) 
Large Intestine Perforation  1/343 (0.29%)  0/334 (0.00%) 
Localised Intraabdominal Fluid Collection  0/343 (0.00%)  1/334 (0.30%) 
Mesenteric Vein Thrombosis  1/343 (0.29%)  0/334 (0.00%) 
Nausea  1/343 (0.29%)  0/334 (0.00%) 
Peritoneal Haemorrhage  1/343 (0.29%)  0/334 (0.00%) 
Portal Hypertensive Gastropathy  0/343 (0.00%)  1/334 (0.30%) 
Stress Ulcer  0/343 (0.00%)  1/334 (0.30%) 
General disorders     
Pyrexia  1/343 (0.29%)  2/334 (0.60%) 
Multi-organ Failure  0/343 (0.00%)  2/334 (0.60%) 
Asthenia  0/343 (0.00%)  1/334 (0.30%) 
Hyperpyrexia  1/343 (0.29%)  0/334 (0.00%) 
Oedema Peripheral  1/343 (0.29%)  0/334 (0.00%) 
Hepatobiliary disorders     
Hepatic Function Abnormal  2/343 (0.58%)  1/334 (0.30%) 
Jaundice Cholestatic  0/343 (0.00%)  2/334 (0.60%) 
Bile Duct Stone  0/343 (0.00%)  1/334 (0.30%) 
Hepatic Failure  0/343 (0.00%)  1/334 (0.30%) 
Hyperbilirubinaemia  1/343 (0.29%)  0/334 (0.00%) 
Jaundice  1/343 (0.29%)  0/334 (0.00%) 
Liver Disorder  1/343 (0.29%)  0/334 (0.00%) 
Liver Injury  0/343 (0.00%)  1/334 (0.30%) 
Infections and infestations     
Pneumonia  1/343 (0.29%)  2/334 (0.60%) 
Cellulitis  2/343 (0.58%)  0/334 (0.00%) 
Liver Abscess  2/343 (0.58%)  0/334 (0.00%) 
Neutropenic Sepsis  2/343 (0.58%)  0/334 (0.00%) 
Peritonitis Bacterial  2/343 (0.58%)  0/334 (0.00%) 
Sepsis  1/343 (0.29%)  1/334 (0.30%) 
Septic Shock  1/343 (0.29%)  1/334 (0.30%) 
Abdominal Infection  0/343 (0.00%)  1/334 (0.30%) 
Anal Abscess  1/343 (0.29%)  0/334 (0.00%) 
Bacteraemia  0/343 (0.00%)  1/334 (0.30%) 
Furuncle  1/343 (0.29%)  0/334 (0.00%) 
Gastritis Viral  1/343 (0.29%)  0/334 (0.00%) 
Infected Cyst  0/343 (0.00%)  1/334 (0.30%) 
Infection  1/343 (0.29%)  0/334 (0.00%) 
Salmonella Sepsis  1/343 (0.29%)  0/334 (0.00%) 
Wound Infection Staphylococcal  0/343 (0.00%)  1/334 (0.30%) 
Injury, poisoning and procedural complications     
Hepatic Rupture  3/343 (0.87%)  0/334 (0.00%) 
Post Procedural Complication  1/343 (0.29%)  2/334 (0.60%) 
Post Procedural Haemorrhage  2/343 (0.58%)  1/334 (0.30%) 
Procedural Pain  1/343 (0.29%)  1/334 (0.30%) 
Wound Complication  1/343 (0.29%)  1/334 (0.30%) 
Biloma  0/343 (0.00%)  1/334 (0.30%) 
Fall  0/343 (0.00%)  1/334 (0.30%) 
Hepatic Function Abnormal  1/343 (0.29%)  0/334 (0.00%) 
Hypotension  0/343 (0.00%)  1/334 (0.30%) 
Puncture Site Haemorrhage  0/343 (0.00%)  1/334 (0.30%) 
Skin laceration  1/343 (0.29%)  0/334 (0.00%) 
Wound Haemorrhage  1/343 (0.29%)  0/334 (0.00%) 
Investigations     
Neutrophil Count Decreased  9/343 (2.62%)  0/334 (0.00%) 
Alanine Aminotransferase Increased  1/343 (0.29%)  0/334 (0.00%) 
Aspartate Aminotransferase Increased  1/343 (0.29%)  0/334 (0.00%) 
Blood Bilirubin Increased  1/343 (0.29%)  0/334 (0.00%) 
Haemoglobin Decreased  1/343 (0.29%)  0/334 (0.00%) 
Platelet Count Decreased  1/343 (0.29%)  0/334 (0.00%) 
White Blood Cell Count Decreased  1/343 (0.29%)  0/334 (0.00%) 
Metabolism and nutrition disorders     
Diabetes Mellitus Inadequate Control  2/343 (0.58%)  0/334 (0.00%) 
Decreased Appetite  0/343 (0.00%)  1/334 (0.30%) 
Hypocalcaemia  0/343 (0.00%)  1/334 (0.30%) 
Hypoglycaemia  0/343 (0.00%)  1/334 (0.30%) 
Hyponatraemia  1/343 (0.29%)  0/334 (0.00%) 
Metabolic Acidosis  1/343 (0.29%)  0/334 (0.00%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal Pain  0/343 (0.00%)  1/334 (0.30%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumour Thrombosis  1/343 (0.29%)  0/334 (0.00%) 
Nervous system disorders     
Hepatic encephalopthy  1/343 (0.29%)  1/334 (0.30%) 
Cerebral Ischaemia  0/343 (0.00%)  1/334 (0.30%) 
Convulsion  1/343 (0.29%)  0/334 (0.00%) 
Depressed Level of Consciousness  1/343 (0.29%)  0/334 (0.00%) 
Haemorrhagic Stroke  1/343 (0.29%)  0/334 (0.00%) 
Transient Ischaemic Attack  0/343 (0.00%)  1/334 (0.30%) 
Psychiatric disorders     
Delirium Tremens  1/343 (0.29%)  0/334 (0.00%) 
Mood Altered  1/343 (0.29%)  0/334 (0.00%) 
Renal and urinary disorders     
Acute Prerenal Failure  1/343 (0.29%)  0/334 (0.00%) 
Renal Failure Acute  1/343 (0.29%)  0/334 (0.00%) 
Urethral Stenosis  1/343 (0.29%)  0/334 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pleural Effusion  2/343 (0.58%)  1/334 (0.30%) 
Aspiration  0/343 (0.00%)  1/334 (0.30%) 
Chronic Obstructive Pulmonary Disease  0/343 (0.00%)  1/334 (0.30%) 
Haemothorax  1/343 (0.29%)  0/334 (0.00%) 
Respiratory Failure  1/343 (0.29%)  0/334 (0.00%) 
Surgical and medical procedures     
Biliary Drainage  0/343 (0.00%)  1/334 (0.30%) 
Vascular disorders     
Hypotension  1/343 (0.29%)  0/334 (0.00%) 
Shock Haemorrhagic  0/343 (0.00%)  1/334 (0.30%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
ThermoDox + RFA Sham + RFA
Affected / at Risk (%) Affected / at Risk (%)
Total   327/343 (95.34%)   301/334 (90.12%) 
Blood and lymphatic system disorders     
Neutropenia  87/343 (25.36%)  6/334 (1.80%) 
Leukopenia  73/343 (21.28%)  5/334 (1.50%) 
Thrombocytopenia  18/343 (5.25%)  2/334 (0.60%) 
Gastrointestinal disorders     
Abdominal Pain  50/343 (14.58%)  62/334 (18.56%) 
Nausea  53/343 (15.45%)  43/334 (12.87%) 
Abdominal Pain Upper  44/343 (12.83%)  44/334 (13.17%) 
Vomiting  35/343 (10.20%)  28/334 (8.38%) 
Constipation  21/343 (6.12%)  15/334 (4.49%) 
Abdominal Distension  15/343 (4.37%)  17/334 (5.09%) 
General disorders     
Pyrexia  56/343 (16.33%)  98/334 (29.34%) 
Fatigue  20/343 (5.83%)  14/334 (4.19%) 
Injury, poisoning and procedural complications     
Procedural Pain  28/343 (8.16%)  39/334 (11.68%) 
Wound Complication  33/343 (9.62%)  33/334 (9.88%) 
Investigations     
Aspartate Aminotransferase Increased  70/343 (20.41%)  70/334 (20.96%) 
Alanine Aminotransferase Increased  61/343 (17.78%)  62/334 (18.56%) 
Blood Bilirubin Increased  29/343 (8.45%)  39/334 (11.68%) 
White Blood Cell Count Decreased  48/343 (13.99%)  12/334 (3.59%) 
Neutrophil Count Decreased  38/343 (11.08%)  9/334 (2.69%) 
Platelet Count Decreased  20/343 (5.83%)  20/334 (5.99%) 
Blood Lactate Dehydrogenase Increased  19/343 (5.54%)  17/334 (5.09%) 
Neutrophil Count Increased  24/343 (7.00%)  8/334 (2.40%) 
White Blood Cell Count Increased  24/343 (7.00%)  5/334 (1.50%) 
Metabolism and nutrition disorders     
Decreased Appetite  32/343 (9.33%)  13/334 (3.89%) 
Renal and urinary disorders     
Haematuria  13/343 (3.79%)  23/334 (6.89%) 
Respiratory, thoracic and mediastinal disorders     
Cough  26/343 (7.58%)  49/334 (14.67%) 
Skin and subcutaneous tissue disorders     
Alopecia  173/343 (50.44%)  2/334 (0.60%) 
Vascular disorders     
Hypertension  18/343 (5.25%)  17/334 (5.09%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Nicholas Borys, M.D. Senior Vice President and Chief Medical Officer
Organization: Celsion Corporation
Phone: 609-896-9100
EMail: nborys@celsion.com
Layout table for additonal information
Responsible Party: Celsion
ClinicalTrials.gov Identifier: NCT00617981    
Other Study ID Numbers: 104-06-301
First Submitted: February 6, 2008
First Posted: February 18, 2008
Results First Submitted: February 3, 2017
Results First Posted: March 24, 2017
Last Update Posted: April 25, 2017