Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

PI-88 in Hepatocellular Carcinoma After Hepatectomy

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: NCT00247728
Recruitment Status : Completed
First Posted : November 2, 2005
Results First Posted : November 12, 2020
Last Update Posted : November 12, 2020
Sponsor:
Collaborator:
Progen Pharmaceuticals
Information provided by (Responsible Party):
Medigen Biotechnology Corporation

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Carcinoma, Hepatocellular
Intervention Drug: PI-88
Enrollment 172
Recruitment Details 215 patients were screened between June 2004 and December 2006. Patients were randomized in balanced blocks per center.
Pre-assignment Details  
Arm/Group Title Group A - Untreated Control Group B - 160 mg PI-88/Day Group C - 250 mg PI-88/Day
Hide Arm/Group Description untreated control with standard of care 160 mg PI-88 via subcutaneous injection for four consecutive days per week, every week 250 mg PI-88 via subcutaneous injection for four consecutive days per week, every week
Period Title: Overall Study
Started 58 57 57
Completed 55 51 43
Not Completed 3 6 14
Arm/Group Title Group A - Untreated Control Group B - 160 mg PI-88/Day Group C - 250 mg PI-88/Day Total
Hide Arm/Group Description untreated control with standard of care, ITT population 160 mg PI-88 via subcutaneous injection for four consecutive days per week, every week, ITT population 250 mg PI-88 via subcutaneous injection for four consecutive days per week, every week, ITT population Total of all reporting groups
Overall Number of Baseline Participants 58 56 54 168
Hide Baseline Analysis Population Description
ITT population, defined as all randomized subjects who had received at least one dose of study medication (if in a treatment arm) and who had undergone at least one study visit following randomization, including an abdominal CT scan.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 58 participants 56 participants 54 participants 168 participants
54.96  (12.54) 51.47  (12.57) 52.41  (12.03) 52.39  (12.38)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 56 participants 54 participants 168 participants
Female
15
  25.9%
10
  17.9%
10
  18.5%
35
  20.8%
Male
43
  74.1%
46
  82.1%
44
  81.5%
133
  79.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Taiwan Number Analyzed 58 participants 56 participants 54 participants 168 participants
58 56 54 168
1.Primary Outcome
Title Tumour Non-recurrence Rate
Hide Description The tumor non-recurrence rate at the end of the 48-week study period
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population, defined as all randomized subjects who had received at least one dose of study medication (if in a treatment arm) and who had undergone at least one study visit following randomization, including an abdominal CT scan.
Arm/Group Title Group A - Untreated Control Group B - 160 mg PI-88/Day Group C - 250 mg PI-88/Day
Hide Arm/Group Description:
untreated control with standard of care
160 mg PI-88 via subcutaneous injection for four consecutive days per week, every week
250 mg PI-88 via subcutaneous injection for four consecutive days per week, every week
Overall Number of Participants Analyzed 58 56 54
Measure Type: Number
Unit of Measure: Participants
32 40 35
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group A - Untreated Control, Group B - 160 mg PI-88/Day
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence (legacy)
Comments Sample size is based on the paper 'Two-stage selection and testing design for comparative clinical trials', Thall, PF, Simon, R and Ellenberg, SS. Biometrika (1988),75,(2),303-310.
Statistical Test of Hypothesis P-Value 0.072
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group A - Untreated Control, Group C - 250 mg PI-88/Day
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence (legacy)
Comments Sample size is based on the paper 'Two-stage selection and testing design for comparative clinical trials', Thall, PF, Simon, R and Ellenberg, SS. Biometrika (1988),75,(2),303-310.
Statistical Test of Hypothesis P-Value 0.298
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
2.Secondary Outcome
Title Time to Recurrence
Hide Description Time to recurrence during the 48-week study period
Time Frame until confirmed tumour recurrence, or for a maximum of 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population, defined as all randomized subjects who had received at least one dose of study medication (if in a treatment arm) and who had undergone at least one study visit following randomization, including an abdominal CT scan.
Arm/Group Title Group A - Untreated Control Group B - 160 mg PI-88/Day Group C - 250 mg PI-88/Day
Hide Arm/Group Description:
Untreated control with standard of care
160 mg PI-88 via subcutaneous injection for four consecutive days per week, every week
160 mg PI-88 via subcutaneous injection for four consecutive days per week, every week
Overall Number of Participants Analyzed 58 56 54
Median (95% Confidence Interval)
Unit of Measure: Weeks
NA [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
[1]

The median TTR was unable to be compared among the three study groups because, in all groups, less than 50% of subjects had documented evidence of tumor recurrence by the end of the study.

of tumor recurrence.

[2]
The median TTR was unable to be compared among the three study groups because, in all groups, less than 50% of subjects had documented evidence of tumor recurrence by the end of the study.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group A - Untreated Control, Group B - 160 mg PI-88/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.087
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.59
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group A - Untreated Control, Group C - 250 mg PI-88/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.653
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.87
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Survival Rate
Hide Description Survival rate at the end of the 48-week study period
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population, defined as all randomized subjects who had received at least one dose of study medication (if in a treatment arm) and who had undergone at least one study visit following randomization, including an abdominal CT scan.
Arm/Group Title Group A - Untreated Control Group B - 160 mg PI-88/Day Group C - 250 mg PI-88/Day
Hide Arm/Group Description:
untreated control with standard of care
160 mg PI-88 via subcutaneous injection for four consecutive days per week, every week
250 mg PI-88 via subcutaneous injection for four consecutive days per week, every week
Overall Number of Participants Analyzed 58 56 54
Measure Type: Number
Unit of Measure: Participants
54 51 51
Time Frame During the course of the study (maximum 48 weeks)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Group A - Untreated Control Group B - 160 mg PI-88/Day Group C - 250 mg PI-88/Day
Hide Arm/Group Description untreated control with standard of care in safety population defined as all randomized subjects, who had at least one assessment following randomization. 160 mg PI-88 via subcutaneous injection for four consecutive days per week, every week, safety population (defined as all randomized subjects, who had at least one assessment following randomization) 250 mg PI-88 via subcutaneous injection for four consecutive days per week, every week, safety population defined as all randomized subjects, who had at least one assessment following randomization
All-Cause Mortality
Group A - Untreated Control Group B - 160 mg PI-88/Day Group C - 250 mg PI-88/Day
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
Group A - Untreated Control Group B - 160 mg PI-88/Day Group C - 250 mg PI-88/Day
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/58 (1.72%)      7/57 (12.28%)      8/57 (14.04%)    
Cardiac disorders       
Myocardial infarction  1 [1]  0/58 (0.00%)  0 1/57 (1.75%)  1 0/57 (0.00%)  0
Tachyarrhythmia  1 [2]  0/58 (0.00%)  0 0/57 (0.00%)  0 1/57 (1.75%)  1
Gastrointestinal disorders       
Ascites  1 [1]  0/58 (0.00%)  0 0/57 (0.00%)  0 1/57 (1.75%)  1
Gastric ulcer hemorrhage  1 [1]  0/58 (0.00%)  0 0/57 (0.00%)  0 1/57 (1.75%)  1
Gastrointestinal hemorrhage  1 [3]  1/58 (1.72%)  1 1/57 (1.75%)  1 0/57 (0.00%)  0
Pancreatitis acute  1 [2]  0/58 (0.00%)  0 0/57 (0.00%)  0 1/57 (1.75%)  1
General disorders       
Edema peripheral  1 [1]  0/58 (0.00%)  0 1/57 (1.75%)  1 0/57 (0.00%)  0
Gingival bleeding  1 [4]  0/58 (0.00%)  0 0/57 (0.00%)  0 1/57 (1.75%)  1
Ileus  1 [5]  0/58 (0.00%)  0 1/57 (1.75%)  1 1/57 (1.75%)  1
Hepatobiliary disorders       
Liver disorder  1 [2]  0/58 (0.00%)  0 1/57 (1.75%)  1 0/57 (0.00%)  0
Infections and infestations       
Carbuncle  1 [2]  0/58 (0.00%)  0 0/57 (0.00%)  0 1/57 (1.75%)  1
Injury, poisoning and procedural complications       
Foot fracture  1 [1]  0/58 (0.00%)  0 1/57 (1.75%)  1 0/57 (0.00%)  0
Pelvic fracture  1 [1]  1/58 (1.72%)  1 0/57 (0.00%)  0 0/57 (0.00%)  0
Radius fracture  1 [1]  0/58 (0.00%)  0 1/57 (1.75%)  1 0/57 (0.00%)  0
Metabolism and nutrition disorders       
Hyperkalemia  1 [2]  0/58 (0.00%)  0 0/57 (0.00%)  0 1/57 (1.75%)  1
Hypocalcemia  1 [2]  0/58 (0.00%)  0 0/57 (0.00%)  0 1/57 (1.75%)  1
Hypoglycemia  1 [1]  0/58 (0.00%)  0 1/57 (1.75%)  1 0/57 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Hepatic neoplasm  1 [4]  0/58 (0.00%)  0 1/57 (1.75%)  1 0/57 (0.00%)  0
Nervous system disorders       
Cerebral infarction  1 [2]  0/58 (0.00%)  0 0/57 (0.00%)  0 1/57 (1.75%)  2
Dizziness  1 [1]  0/58 (0.00%)  0 1/57 (1.75%)  1 0/57 (0.00%)  0
Hemorrhage intracranial  1 [4]  0/58 (0.00%)  0 0/57 (0.00%)  0 1/57 (1.75%)  1
Hepatic encephalopathy  1 [2]  0/58 (0.00%)  0 1/57 (1.75%)  1 0/57 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Pneumonia  1 [1]  0/58 (0.00%)  0 1/57 (1.75%)  1 0/57 (0.00%)  0
Respiratory Failure  1 [1]  0/58 (0.00%)  0 1/57 (1.75%)  1 0/57 (0.00%)  0
Vascular disorders       
Hemorrhage  1 [4]  0/58 (0.00%)  0 0/57 (0.00%)  0 1/57 (1.75%)  1
Hypovalemic shock  1 [2]  0/58 (0.00%)  0 0/57 (0.00%)  0 1/57 (1.75%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v9.0
[1]
Unrelated to treatment
[2]
Unlikely related to treatment
[3]
Unrelated to treatment (group A); unlikely related to treatment (group B)
[4]
Possibly related
[5]
Unrelated to treatment (group B); unlikely related to treatment (group C)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Group A - Untreated Control Group B - 160 mg PI-88/Day Group C - 250 mg PI-88/Day
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   44/58 (75.86%)      55/57 (96.49%)      54/57 (94.74%)    
Blood and lymphatic system disorders       
Neutropenia  1  0/58 (0.00%)  0 6/57 (10.53%)  20 4/57 (7.02%)  24
Splenomegaly  1  3/58 (5.17%)  3 7/57 (12.28%)  7 3/57 (5.26%)  3
Thrombocytopenia  1  1/58 (1.72%)  1 6/57 (10.53%)  14 7/57 (12.28%)  18
Gastrointestinal disorders       
Abdominal discomfort  1  1/58 (1.72%)  1 8/57 (14.04%)  8 1/57 (1.75%)  1
Abdominal distension  1  5/58 (8.62%)  5 6/57 (10.53%)  6 5/57 (8.77%)  5
Abdominal pain  1  4/58 (6.90%)  5 6/57 (10.53%)  6 5/57 (8.77%)  6
Abdominal pain upper  1  1/58 (1.72%)  1 5/57 (8.77%)  7 8/57 (14.04%)  8
Ascites  1  1/58 (1.72%)  1 6/57 (10.53%)  9 4/57 (7.02%)  8
Diarrhoea  1  1/58 (1.72%)  1 7/57 (12.28%)  9 3/57 (5.26%)  3
Nausea  1  1/58 (1.72%)  1 0/57 (0.00%)  0 5/57 (8.77%)  5
Periodontits  1  0/58 (0.00%)  0 3/57 (5.26%)  3 0/57 (0.00%)  0
General disorders       
Fatigue  1  1/58 (1.72%)  1 3/57 (5.26%)  3 3/57 (5.26%)  6
Injection site haemorrhage  1  0/58 (0.00%)  0 7/57 (12.28%)  8 9/57 (15.79%)  9
Injection site pain  1  0/58 (0.00%)  0 6/57 (10.53%)  6 4/57 (7.02%)  4
Injection site reaction  1  0/58 (0.00%)  0 4/57 (7.02%)  6 4/57 (7.02%)  4
Malaise  1  3/58 (5.17%)  3 4/57 (7.02%)  5 5/57 (8.77%)  6
Oedema peripheral  1  1/58 (1.72%)  1 4/57 (7.02%)  4 4/57 (7.02%)  7
Infections and infestations       
Nasopharyngitis  1  1/58 (1.72%)  2 1/57 (1.75%)  3 3/57 (5.26%)  3
Upper respiratory tract infection  1  14/58 (24.14%)  15 8/57 (14.04%)  8 10/57 (17.54%)  12
Injury, poisoning and procedural complications       
Wound complication  1  2/58 (3.45%)  3 5/57 (8.77%)  5 2/57 (3.51%)  2
Investigations       
ALT increased  1  4/58 (6.90%)  6 14/57 (24.56%)  21 19/57 (33.33%)  33
APPT prolonged  1  0/58 (0.00%)  0 20/57 (35.09%)  20 18/57 (31.58%)  22
AST increased  1  3/58 (5.17%)  3 10/57 (17.54%)  18 13/57 (22.81%)  24
Hepatic enzyme increased  1  0/58 (0.00%)  0 0/57 (0.00%)  0 3/57 (5.26%)  4
PT prolongation  1  0/58 (0.00%)  0 0/57 (0.00%)  0 3/57 (5.26%)  3
Metabolism and nutrition disorders       
Hyperalbuminaemia  1  1/58 (1.72%)  1 3/57 (5.26%)  5 1/57 (1.75%)  1
Musculoskeletal and connective tissue disorders       
Arthralgia  1  3/58 (5.17%)  3 3/57 (5.26%)  3 1/57 (1.75%)  2
Back pain  1  2/58 (3.45%)  2 2/57 (3.51%)  2 5/57 (8.77%)  6
Muscle spasms  1  0/58 (0.00%)  0 2/57 (3.51%)  2 3/57 (5.26%)  4
Musculoskeletal pain  1  0/58 (0.00%)  0 4/57 (7.02%)  4 1/57 (1.75%)  1
Nervous system disorders       
Dizziness  1  5/58 (8.62%)  6 1/57 (1.75%)  2 6/57 (10.53%)  6
Headache  1  2/58 (3.45%)  3 3/57 (5.26%)  3 4/57 (7.02%)  4
Psychiatric disorders       
Insomnia  1  10/58 (17.24%)  10 11/57 (19.30%)  13 11/57 (19.30%)  16
Sleep disorders  1  1/58 (1.72%)  1 1/57 (1.75%)  1 3/57 (5.26%)  3
Renal and urinary disorders       
Nephrolithiasis  1  2/58 (3.45%)  2 3/57 (5.26%)  3 0/57 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Cough  1  7/58 (12.07%)  7 5/57 (8.77%)  8 5/57 (8.77%)  6
Dyspnoea  1  2/58 (3.45%)  2 3/57 (5.26%)  3 1/57 (1.75%)  1
Pharyngolaryngeal pain  1  0/58 (0.00%)  0 3/57 (5.26%)  4 1/57 (1.75%)  1
Pleural effusion  1  0/58 (0.00%)  0 5/57 (8.77%)  5 1/57 (1.75%)  1
Skin and subcutaneous tissue disorders       
Alopecia  1  0/58 (0.00%)  0 6/57 (10.53%)  7 13/57 (22.81%)  13
Puritus  1  1/58 (1.72%)  1 2/57 (3.51%)  2 7/57 (12.28%)  7
Rash  1  1/58 (1.72%)  1 1/57 (1.75%)  1 3/57 (5.26%)  3
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v9.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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: Director of Regulatory Affairs and Clinical Development
Organization: Progen Pharmaceuticals Ltd
Phone: +61 (0)7 38423333
EMail: darrynb@progen-pharma.com
Layout table for additonal information
Responsible Party: Medigen Biotechnology Corporation
ClinicalTrials.gov Identifier: NCT00247728    
Other Study ID Numbers: MG 002
PR88204 ( Other Identifier: Alternate protocol identifier set by company )
First Submitted: November 1, 2005
First Posted: November 2, 2005
Results First Submitted: July 27, 2011
Results First Posted: November 12, 2020
Last Update Posted: November 12, 2020