Trial Outcomes & Findings for A Study of Recombinant Vaccinia Virus to Treat Unresectable Primary Hepatocellular Carcinoma (NCT NCT00554372)
NCT ID: NCT00554372
Last Updated: 2016-02-04
Results Overview
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.
COMPLETED
PHASE2
30 participants
Initial progression status and response assessment at 8 weeks from first dose
2016-02-04
Participant Flow
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.
Participant milestones
| Measure |
Low Dose
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.
|
High Dose
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 Study
STARTED
|
14
|
16
|
|
Overall Study
COMPLETED
|
14
|
16
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of Recombinant Vaccinia Virus to Treat Unresectable Primary Hepatocellular Carcinoma
Baseline characteristics by cohort
| Measure |
Low Dose
n=14 Participants
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.
|
High Dose
n=16 Participants
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
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
67.1 years
STANDARD_DEVIATION 11.5 • n=5 Participants
|
62.9 years
STANDARD_DEVIATION 12.7 • n=7 Participants
|
64.9 years
STANDARD_DEVIATION 12.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
5 participants
n=5 Participants
|
5 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
3 participants
n=5 Participants
|
4 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Region of Enrollment
Korea, Republic of
|
6 participants
n=5 Participants
|
7 participants
n=7 Participants
|
13 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Initial progression status and response assessment at 8 weeks from first dosePopulation: 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
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.
Outcome measures
| Measure |
Low Dose
n=13 Participants
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.
|
High Dose
n=15 Participants
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.
|
|---|---|---|
|
Proportion of Subjects Achieving Disease Control (Non-progressive Disease) at 8 Weeks After Initiation of Treatment
|
0.7273 Proportion of evaluable participants
Interval 0.39 to 0.94
|
0.6429 Proportion of evaluable participants
Interval 0.351 to 0.872
|
SECONDARY outcome
Timeframe: Safety and tolerability were evaluated throughout the 8 week period of study participationTreatment-related serious adverse events in patients treated at two dose levels
Outcome measures
| Measure |
Low Dose
n=14 Participants
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.
|
High Dose
n=16 Participants
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.
|
|---|---|---|
|
Safety and Tolerability of JX-594 Administered at Two Dose Levels
|
1 serious adverse event
|
0 serious adverse event
|
SECONDARY outcome
Timeframe: At week 8Number 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.
Outcome measures
| Measure |
Low Dose
n=13 Participants
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.
|
High Dose
n=15 Participants
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.
|
|---|---|---|
|
Number of Subjects Achieving Disease Control as Determined Using Intrahepatic Modified RECIST Criteria
|
6 participants
|
7 participants
|
SECONDARY outcome
Timeframe: To 760 days post treatmentOverall survival after treatment in days
Outcome measures
| Measure |
Low Dose
n=13 Participants
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.
|
High Dose
n=16 Participants
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.
|
|---|---|---|
|
Median Overall Survival
|
202 days
Interval 109.0 to 271.0
|
423 days
Interval 265.0 to
Upper bound was not achieved. The data analysis was done at a time when subjects in both dose groups were still alive.
|
Adverse Events
Low Dose
High Dose
Serious adverse events
| Measure |
Low Dose
n=14 participants at risk
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.
|
High Dose
n=16 participants at risk
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.
|
|---|---|---|
|
Hepatobiliary disorders
Bile duct Obstruction
|
0.00%
0/14 • 8 weeks
|
12.5%
2/16 • 8 weeks
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
Blood and lymphatic system disorders
Anemia
|
7.1%
1/14 • 8 weeks
|
0.00%
0/16 • 8 weeks
|
|
Cardiac disorders
Angina pectoris
|
7.1%
1/14 • 8 weeks
|
0.00%
0/16 • 8 weeks
|
|
Cardiac disorders
Myocardial Infarction
|
7.1%
1/14 • 8 weeks
|
0.00%
0/16 • 8 weeks
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
Infections and infestations
Bacteraemia
|
7.1%
1/14 • 8 weeks
|
0.00%
0/16 • 8 weeks
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
Nervous system disorders
Hepatic Encephalopathy
|
7.1%
1/14 • 8 weeks
|
0.00%
0/16 • 8 weeks
|
Other adverse events
| Measure |
Low Dose
n=14 participants at risk
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.
|
High Dose
n=16 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Lymphopenia
|
28.6%
4/14 • 8 weeks
|
18.8%
3/16 • 8 weeks
|
|
Cardiac disorders
Tachycardia
|
21.4%
3/14 • 8 weeks
|
12.5%
2/16 • 8 weeks
|
|
Gastrointestinal disorders
Nausea
|
35.7%
5/14 • 8 weeks
|
50.0%
8/16 • 8 weeks
|
|
Gastrointestinal disorders
Vomiting
|
57.1%
8/14 • 8 weeks
|
37.5%
6/16 • 8 weeks
|
|
Gastrointestinal disorders
Abdominal Pain
|
21.4%
3/14 • 8 weeks
|
31.2%
5/16 • 8 weeks
|
|
Gastrointestinal disorders
Dyspepsia
|
7.1%
1/14 • 8 weeks
|
18.8%
3/16 • 8 weeks
|
|
General disorders
Pyrexia
|
92.9%
13/14 • 8 weeks
|
100.0%
16/16 • 8 weeks
|
|
General disorders
Chills
|
78.6%
11/14 • 8 weeks
|
81.2%
13/16 • 8 weeks
|
|
General disorders
Influenza like illness
|
28.6%
4/14 • 8 weeks
|
25.0%
4/16 • 8 weeks
|
|
Injury, poisoning and procedural complications
Injection site pain
|
42.9%
6/14 • 8 weeks
|
56.2%
9/16 • 8 weeks
|
|
General disorders
Fatigue
|
28.6%
4/14 • 8 weeks
|
37.5%
6/16 • 8 weeks
|
|
General disorders
Asthenia
|
7.1%
1/14 • 8 weeks
|
12.5%
2/16 • 8 weeks
|
|
Hepatobiliary disorders
Hyperbilirubinemia
|
14.3%
2/14 • 8 weeks
|
12.5%
2/16 • 8 weeks
|
|
Investigations
Hemoglobin Decreased
|
21.4%
3/14 • 8 weeks
|
12.5%
2/16 • 8 weeks
|
|
Metabolism and nutrition disorders
Anorexia
|
14.3%
2/14 • 8 weeks
|
43.8%
7/16 • 8 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.1%
1/14 • 8 weeks
|
18.8%
3/16 • 8 weeks
|
|
Nervous system disorders
Headache
|
35.7%
5/14 • 8 weeks
|
37.5%
6/16 • 8 weeks
|
|
Psychiatric disorders
Confusional state
|
14.3%
2/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
21.4%
3/14 • 8 weeks
|
12.5%
2/16 • 8 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
14.3%
2/14 • 8 weeks
|
18.8%
3/16 • 8 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
21.4%
3/14 • 8 weeks
|
12.5%
2/16 • 8 weeks
|
|
Vascular disorders
Hypertension
|
28.6%
4/14 • 8 weeks
|
18.8%
3/16 • 8 weeks
|
|
Vascular disorders
Hypotension
|
14.3%
2/14 • 8 weeks
|
18.8%
3/16 • 8 weeks
|
|
Metabolism and nutrition disorders
Hyponatremia
|
21.4%
3/14 • 8 weeks
|
12.5%
2/16 • 8 weeks
|
|
General disorders
Edema peripheral
|
21.4%
3/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
General disorders
Chest Discomfort
|
7.1%
1/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
General disorders
Pain
|
14.3%
2/14 • 8 weeks
|
0.00%
0/16 • 8 weeks
|
|
Gastrointestinal disorders
Constipation
|
21.4%
3/14 • 8 weeks
|
31.2%
5/16 • 8 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
7.1%
1/14 • 8 weeks
|
31.2%
5/16 • 8 weeks
|
|
Gastrointestinal disorders
Abdominal Pain (lower)
|
14.3%
2/14 • 8 weeks
|
0.00%
0/16 • 8 weeks
|
|
Gastrointestinal disorders
Mouth Ulceration
|
7.1%
1/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
Gastrointestinal disorders
Stomach Discomfort
|
0.00%
0/14 • 8 weeks
|
12.5%
2/16 • 8 weeks
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
14.3%
2/14 • 8 weeks
|
0.00%
0/16 • 8 weeks
|
|
Blood and lymphatic system disorders
Anemia
|
7.1%
1/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
Renal and urinary disorders
Urinary retention
|
7.1%
1/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
28.6%
4/14 • 8 weeks
|
12.5%
2/16 • 8 weeks
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
21.4%
3/14 • 8 weeks
|
12.5%
2/16 • 8 weeks
|
|
Metabolism and nutrition disorders
Hypokalemia
|
14.3%
2/14 • 8 weeks
|
12.5%
2/16 • 8 weeks
|
|
Metabolism and nutrition disorders
Dehydration
|
14.3%
2/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
14.3%
2/14 • 8 weeks
|
0.00%
0/16 • 8 weeks
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
7.1%
1/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
Investigations
Aspartate aminotransferse increased
|
28.6%
4/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
Investigations
Lymphocyte count decreased
|
7.1%
1/14 • 8 weeks
|
12.5%
2/16 • 8 weeks
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/14 • 8 weeks
|
12.5%
2/16 • 8 weeks
|
|
Investigations
Blood Alkaline Phosphatase increased
|
7.1%
1/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
Investigations
Hemoglobin
|
7.1%
1/14 • 8 weeks
|
12.5%
2/16 • 8 weeks
|
|
Investigations
Hematocrit decreased
|
7.1%
1/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
Investigations
Platelet Count decreased
|
7.1%
1/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
Investigations
White blood cell count decreased
|
14.3%
2/14 • 8 weeks
|
0.00%
0/16 • 8 weeks
|
|
Investigations
White blood cell count increased
|
7.1%
1/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
21.4%
3/14 • 8 weeks
|
25.0%
4/16 • 8 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscoskeletal Pain
|
21.4%
3/14 • 8 weeks
|
12.5%
2/16 • 8 weeks
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
0.00%
0/14 • 8 weeks
|
12.5%
2/16 • 8 weeks
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
14.3%
2/14 • 8 weeks
|
0.00%
0/16 • 8 weeks
|
|
Musculoskeletal and connective tissue disorders
Pain in Jaw
|
7.1%
1/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
Nervous system disorders
Dizziness
|
14.3%
2/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
28.6%
4/14 • 8 weeks
|
6.2%
1/16 • 8 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
14.3%
2/14 • 8 weeks
|
0.00%
0/16 • 8 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/14 • 8 weeks
|
12.5%
2/16 • 8 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
14.3%
2/14 • 8 weeks
|
0.00%
0/16 • 8 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Productive Cough
|
14.3%
2/14 • 8 weeks
|
0.00%
0/16 • 8 weeks
|
|
Psychiatric disorders
Insomnia
|
7.1%
1/14 • 8 weeks
|
18.8%
3/16 • 8 weeks
|
|
Psychiatric disorders
Anxiety
|
14.3%
2/14 • 8 weeks
|
0.00%
0/16 • 8 weeks
|
|
Ear and labyrinth disorders
Ear Pain
|
0.00%
0/14 • 8 weeks
|
12.5%
2/16 • 8 weeks
|
Additional Information
Manager, IP, Contracts, Translational Research
SillaJen Biotherapeutics, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60