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A Study of Recombinant Vaccinia Virus to Treat Unresectable Primary Hepatocellular Carcinoma

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ClinicalTrials.gov Identifier: NCT00554372
Recruitment Status : Completed
First Posted : November 6, 2007
Results First Posted : August 17, 2015
Last Update Posted : February 4, 2016
Sponsor:
Information provided by (Responsible Party):
SillaJen, Inc. ( Jennerex Biotherapeutics )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Carcinoma, Hepatocellular
Intervention Genetic: JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF)
Enrollment 30
Recruitment Details  
Pre-assignment Details Subjects were randomized 1:1 to a treatment arm (dosage group). Randomization into the dosing groups was stratified by whether the Hepatocellular carcinoma was virally associated (hepatitis B virus or hepatitis C virus) or not virally associated.
Arm/Group Title Low Dose High Dose
Hide Arm/Group Description 1e8 pfu (plaque forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart). Each treatment dose was divided among 1-5 hepatic tumors; all tumors injected at day 1 were also injected at subsequent treatments. 1e9 pfu (plaque forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart). Each treatment dose was divided among 1-5 hepatic tumors; all tumors injected at day 1 were also injected at subsequent treatments.
Period Title: Overall Study
Started 14 16
Completed 14 16
Not Completed 0 0
Arm/Group Title Low Dose High Dose Total
Hide Arm/Group Description 1e8 pfu (plaque forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart). Each treatment dose was divided among 1-5 hepatic tumors; all tumors injected at day 1 were also injected at subsequent treatments. 1e9 pfu (plaque forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart). Each treatment dose was divided among 1-5 hepatic tumors; all tumors injected at day 1 were also injected at subsequent treatments. Total of all reporting groups
Overall Number of Baseline Participants 14 16 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 14 participants 16 participants 30 participants
67.1  (11.5) 62.9  (12.7) 64.9  (12.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 16 participants 30 participants
Female
4
  28.6%
3
  18.8%
7
  23.3%
Male
10
  71.4%
13
  81.3%
23
  76.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 14 participants 16 participants 30 participants
United States 5 5 10
Canada 3 4 7
Korea, Republic of 6 7 13
1.Primary Outcome
Title Proportion of Subjects Achieving Disease Control (Non-progressive Disease) at 8 Weeks After Initiation of Treatment
Hide Description Proportion of subjects achieving disease control at 8 weeks based on a modified Response Evaluation Criteria in Solid Tumors v1.0 (mRECIST). Per mRECIST for target lesions as assessed by dynamic contrast enhanced dynamic MRI: Complete Response (CR), Disappearance of all tumor(s); Partial Response (PR), >=30% decrease in the sum of longest diameter (LD) of tumor(s) taking as reference the baseline sum; Stable Disease (SD), any cases that do not qualify for PR or progressive disease (PD); PD, any increase of >= 20% in the sum of longest diameter (LD) of tumor(s) taking as reference the baseline sum. Disease Control (DC) = CR or PR or SD. For mRECIST criteria, new tumor(s) that developed within the liver were measured (a new tumor was defined as a malignant tumor not present at baseline, was ≥ 1 cm in LD had typical hypervascular features of HCC). Their maximum diameter(s) were included in the sum of the maximum diameter; new tumors were not considered evidence for progression.
Time Frame Initial progression status and response assessment at 8 weeks from first dose
Hide Outcome Measure Data
Hide Analysis Population Description
Patients having evaluable radiographic imaging, 2 patients in each arm were excluded due to unevaluable images, 1 patient in the low dose arm was excluded due to a protocol deviation
Arm/Group Title Low Dose High Dose
Hide Arm/Group Description:
1e8 pfu (plaque forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart). Each treatment dose was divided among 1-5 hepatic tumors; all tumors injected at day 1 were also injected at subsequent treatments.
1e9 pfu (plaque forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart). Each treatment dose was divided among 1-5 hepatic tumors; all tumors injected at day 1 were also injected at subsequent treatments.
Overall Number of Participants Analyzed 13 15
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of evaluable participants
0.7273
(0.390 to 0.940)
0.6429
(0.351 to 0.872)
2.Secondary Outcome
Title Safety and Tolerability of JX-594 Administered at Two Dose Levels
Hide Description Treatment-related serious adverse events in patients treated at two dose levels
Time Frame Safety and tolerability were evaluated throughout the 8 week period of study participation
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Low Dose High Dose
Hide Arm/Group Description:

1e8 pfu (plaque forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart)

JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF): Patients will be randomized 1:1 to one of two total doses (1e8 or 1e9 pfu)and injected intratumorally in 1-5 intrahepatic tumors on Days 1, 15, and 29.

1e9 pfu (plaque-forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart)

JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF): Patients will be randomized 1:1 to one of two total doses (1e8 or 1e9 pfu)and injected intratumorally in 1-5 intrahepatic tumors on Days 1, 15, and 29.

Overall Number of Participants Analyzed 14 16
Measure Type: Number
Unit of Measure: serious adverse event
1 0
3.Secondary Outcome
Title Number of Subjects Achieving Disease Control as Determined Using Intrahepatic Modified RECIST Criteria
Hide Description

Number of subjects achieving disease control (non-progressive disease) at 8 weeks after treatment was initiated based on modified Response Evaluation Criteria in Solid Tumors for Hepatocellular Carcinoma (mRECIST for HCC). mRECIST for HCC adopted the concept of viable tumor as tumor tissue showing uptake in arterial phase of contrast enhanced radiologic imaging techniques. (see Lencioni and Llovet, Semin. Liver Dis. 2010; 30:52-60). Per mRECIST for HCC, for target lesions as assessed by contrast enhanced dynamic MRI: Complete Response (CR), Disappearance of any intratumoral arterial enhancement in all target (viable) lesions; Partial Response (PR), >=30% decrease in the sum of diameters of viable target lesions; Stable Disease (SD), any cases that do not qualify for PR or progressive disease (PD); PD, any increase of >= 20% in viable target lesions.

Disease Control (DC) = CR or PR or SD.

Time Frame At week 8
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Low Dose High Dose
Hide Arm/Group Description:
1e8 pfu (plaque forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart). Each treatment dose was divided among 1-5 hepatic tumors; all tumors injected at day 1 were also injected at subsequent treatments.
1e9 pfu (plaque forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart). Each treatment dose was divided among 1-5 hepatic tumors; all tumors injected at day 1 were also injected at subsequent treatments.
Overall Number of Participants Analyzed 13 15
Measure Type: Number
Unit of Measure: participants
6 7
4.Secondary Outcome
Title Median Overall Survival
Hide Description Overall survival after treatment in days
Time Frame To 760 days post treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Low Dose High Dose
Hide Arm/Group Description:
1e8 pfu (plaque forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart). Each treatment dose was divided among 1-5 hepatic tumors; all tumors injected at day 1 were also injected at subsequent treatments.
1e9 pfu (plaque forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart). Each treatment dose was divided among 1-5 hepatic tumors; all tumors injected at day 1 were also injected at subsequent treatments.
Overall Number of Participants Analyzed 13 16
Median (95% Confidence Interval)
Unit of Measure: days
202
(109 to 271)
423 [1] 
(265 to NA)
[1]
Upper bound was not achieved. The data analysis was done at a time when subjects in both dose groups were still alive.
Time Frame 8 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Low Dose High Dose
Hide Arm/Group Description 1e8 pfu (plaque forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart). Each treatment dose was divided among 1-5 hepatic tumors; all tumors injected at day 1 were also injected at subsequent treatments. 1e9 pfu (plaque forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart). Each treatment dose was divided among 1-5 hepatic tumors; all tumors injected at day 1 were also injected at subsequent treatments.
All-Cause Mortality
Low Dose High Dose
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Low Dose High Dose
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/14 (28.57%)      4/16 (25.00%)    
Blood and lymphatic system disorders     
Anemia  1  1/14 (7.14%)  0/16 (0.00%)  0
Cardiac disorders     
Angina pectoris  1  1/14 (7.14%)  0/16 (0.00%)  0
Myocardial Infarction  1  1/14 (7.14%)  0/16 (0.00%)  0
Gastrointestinal disorders     
Nausea  1  0/14 (0.00%)  0 1/16 (6.25%) 
Vomiting  1  0/14 (0.00%)  0 1/16 (6.25%) 
Hepatobiliary disorders     
Bile duct Obstruction  1  0/14 (0.00%)  2/16 (12.50%) 
Hyperbilirubinaemia  1  0/14 (0.00%)  0 1/16 (6.25%) 
Infections and infestations     
Bacteraemia  1  1/14 (7.14%)  0/16 (0.00%)  0
Metabolism and nutrition disorders     
Hyponatraemia  1  0/14 (0.00%)  0 1/16 (6.25%) 
Nervous system disorders     
Hepatic Encephalopathy  1  1/14 (7.14%)  0/16 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Low Dose High Dose
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/14 (100.00%)      16/16 (100.00%)    
Blood and lymphatic system disorders     
Lymphopenia  1  4/14 (28.57%)  3/16 (18.75%) 
Anemia  1  1/14 (7.14%)  1/16 (6.25%) 
Cardiac disorders     
Tachycardia  1  3/14 (21.43%)  2/16 (12.50%) 
Ear and labyrinth disorders     
Ear Pain  1  0/14 (0.00%)  2/16 (12.50%) 
Gastrointestinal disorders     
Nausea  1  5/14 (35.71%)  8/16 (50.00%) 
Vomiting  1  8/14 (57.14%)  6/16 (37.50%) 
Abdominal Pain  1  3/14 (21.43%)  5/16 (31.25%) 
Dyspepsia  1  1/14 (7.14%)  3/16 (18.75%) 
Constipation  1  3/14 (21.43%)  5/16 (31.25%) 
Diarrhea  1  1/14 (7.14%)  5/16 (31.25%) 
Abdominal Pain (lower)  1  2/14 (14.29%)  0/16 (0.00%) 
Mouth Ulceration  1  1/14 (7.14%)  1/16 (6.25%) 
Stomach Discomfort  1  0/14 (0.00%)  2/16 (12.50%) 
Abdominal Pain Upper  1  3/14 (21.43%)  4/16 (25.00%) 
General disorders     
Pyrexia  1  13/14 (92.86%)  16/16 (100.00%) 
Chills  1  11/14 (78.57%)  13/16 (81.25%) 
Influenza like illness  1  4/14 (28.57%)  4/16 (25.00%) 
Fatigue  1  4/14 (28.57%)  6/16 (37.50%) 
Asthenia  1  1/14 (7.14%)  2/16 (12.50%) 
Edema peripheral  1  3/14 (21.43%)  1/16 (6.25%) 
Chest Discomfort  1  1/14 (7.14%)  1/16 (6.25%) 
Pain  1  2/14 (14.29%)  0/16 (0.00%) 
Hepatobiliary disorders     
Hyperbilirubinemia  1  2/14 (14.29%)  2/16 (12.50%) 
Injury, poisoning and procedural complications     
Injection site pain  1  6/14 (42.86%)  9/16 (56.25%) 
Investigations     
Hemoglobin Decreased  1  3/14 (21.43%)  2/16 (12.50%) 
Aspartate aminotransferse increased  1  4/14 (28.57%)  1/16 (6.25%) 
Lymphocyte count decreased  1  1/14 (7.14%)  2/16 (12.50%) 
Alanine aminotransferase increased  1  0/14 (0.00%)  2/16 (12.50%) 
Blood Alkaline Phosphatase increased  1  1/14 (7.14%)  1/16 (6.25%) 
Hemoglobin  1  1/14 (7.14%)  2/16 (12.50%) 
Hematocrit decreased  1  1/14 (7.14%)  1/16 (6.25%) 
Platelet Count decreased  1  1/14 (7.14%)  1/16 (6.25%) 
White blood cell count decreased  1  2/14 (14.29%)  0/16 (0.00%) 
White blood cell count increased  1  1/14 (7.14%)  1/16 (6.25%) 
Metabolism and nutrition disorders     
Anorexia  1  2/14 (14.29%)  7/16 (43.75%) 
Hyponatremia  1  3/14 (21.43%)  2/16 (12.50%) 
Hyperglycemia  1  4/14 (28.57%)  2/16 (12.50%) 
Hypoalbuminemia  1  3/14 (21.43%)  2/16 (12.50%) 
Hypokalemia  1  2/14 (14.29%)  2/16 (12.50%) 
Dehydration  1  2/14 (14.29%)  1/16 (6.25%) 
Decreased Appetite  1  2/14 (14.29%)  0/16 (0.00%) 
Hyperkalemia  1  1/14 (7.14%)  1/16 (6.25%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/14 (7.14%)  3/16 (18.75%) 
Muscoskeletal Pain  1  3/14 (21.43%)  2/16 (12.50%) 
Neck Pain  1  0/14 (0.00%)  2/16 (12.50%) 
Pain in Extremity  1  2/14 (14.29%)  0/16 (0.00%) 
Pain in Jaw  1  1/14 (7.14%)  1/16 (6.25%) 
Nervous system disorders     
Headache  1  5/14 (35.71%)  6/16 (37.50%) 
Dizziness  1  2/14 (14.29%)  1/16 (6.25%) 
Psychiatric disorders     
Confusional state  1  2/14 (14.29%)  1/16 (6.25%) 
Insomnia  1  1/14 (7.14%)  3/16 (18.75%) 
Anxiety  1  2/14 (14.29%)  0/16 (0.00%) 
Renal and urinary disorders     
Urinary retention  1  1/14 (7.14%)  1/16 (6.25%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  3/14 (21.43%)  2/16 (12.50%) 
Cough  1  4/14 (28.57%)  1/16 (6.25%) 
Hypoxia  1  2/14 (14.29%)  0/16 (0.00%) 
Oropharyngeal pain  1  0/14 (0.00%)  2/16 (12.50%) 
Pneumothorax  1  2/14 (14.29%)  0/16 (0.00%) 
Productive Cough  1  2/14 (14.29%)  0/16 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash  1  2/14 (14.29%)  3/16 (18.75%) 
Pruritus  1  3/14 (21.43%)  2/16 (12.50%) 
Hyperhidrosis  1  2/14 (14.29%)  0/16 (0.00%) 
Vascular disorders     
Hypertension  1  4/14 (28.57%)  3/16 (18.75%) 
Hypotension  1  2/14 (14.29%)  3/16 (18.75%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
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: Manager, IP, Contracts, Translational Research
Organization: SillaJen Biotherapeutics, Inc.
Phone: 415 281 8886
EMail: tchiaverotti@sillajen.com
Layout table for additonal information
Responsible Party: SillaJen, Inc. ( Jennerex Biotherapeutics )
ClinicalTrials.gov Identifier: NCT00554372     History of Changes
Other Study ID Numbers: JX594-IT-HEP007
First Submitted: November 2, 2007
First Posted: November 6, 2007
Results First Submitted: May 12, 2015
Results First Posted: August 17, 2015
Last Update Posted: February 4, 2016