Trial Outcomes & Findings for Trial of PI-88 With Dacarbazine in Patients With Metastatic Melanoma (NCT NCT00130442)
NCT ID: NCT00130442
Last Updated: 2022-06-23
Results Overview
The Proportion of Patients With Objective Response or Stable Disease (Non-progression Rate) after six treatment cycles
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
134 participants
Primary outcome timeframe
In week 3 of every second cycle (each cycle was 21 days) for all subjects enrolled, up to the end of cycle 6 (About 5 months after randomization)
Results posted on
2022-06-23
Participant Flow
Participant milestones
| Measure |
Arm 1- PI-88 Plus Dacarbazine
PI-88 (muparfostat) 190 mg daily by subcutaneous injection and dacarbazine 1000 mg/m2 on day 1 of each 21 day cycle
PI-88 and dacarbazine: 190 mg daily by subcutaneous injection for PI-88 and 1000 mg/m2 on day 1 of each 21 day cycle by intravenous infusion
|
Arm 2- Dacarbazine Alone
dacarbazine 1000 mg/m2 on day 1 of every 21 day cycle by intravenous infusion
dacarbazine or DTIC: intravenous infusion 1000 mg/m2 on day 1 of every 21 day cycle
|
|---|---|---|
|
Overall Study
STARTED
|
66
|
68
|
|
Overall Study
COMPLETED
|
65
|
66
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Arm 1- PI-88 Plus Dacarbazine
PI-88 (muparfostat) 190 mg daily by subcutaneous injection and dacarbazine 1000 mg/m2 on day 1 of each 21 day cycle
PI-88 and dacarbazine: 190 mg daily by subcutaneous injection for PI-88 and 1000 mg/m2 on day 1 of each 21 day cycle by intravenous infusion
|
Arm 2- Dacarbazine Alone
dacarbazine 1000 mg/m2 on day 1 of every 21 day cycle by intravenous infusion
dacarbazine or DTIC: intravenous infusion 1000 mg/m2 on day 1 of every 21 day cycle
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
|
Overall Study
did not meet criteria
|
1
|
1
|
Baseline Characteristics
Trial of PI-88 With Dacarbazine in Patients With Metastatic Melanoma
Baseline characteristics by cohort
| Measure |
Arm 1- PI-88 Plus Dacarbazine
n=65 Participants
PI-88 (muparfostat) 190 mg daily by subcutaneous injection and dacarbazine 1000 mg/m2 on day 1 of each 21 day cycle
PI-88 and dacarbazine: 190 mg daily by subcutaneous injection for PI-88 and 1000 mg/m2 on day 1 of each 21 day cycle by intravenous infusion
|
Arm 2- Dacarbazine Alone
n=66 Participants
dacarbazine 1000 mg/m2 on day 1 of every 21 day cycle by intravenous infusion
dacarbazine or DTIC: intravenous infusion 1000 mg/m2 on day 1 of every 21 day cycle
|
Total
n=131 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.4 years
STANDARD_DEVIATION 13.26 • n=5 Participants
|
57.9 years
STANDARD_DEVIATION 13.07 • n=7 Participants
|
59.1 years
STANDARD_DEVIATION 13.17 • n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
50 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
89 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
63 Participants
n=5 Participants
|
65 Participants
n=7 Participants
|
128 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Height
|
174.0 cm
STANDARD_DEVIATION 8.11 • n=5 Participants
|
171.2 cm
STANDARD_DEVIATION 9.57 • n=7 Participants
|
172.6 cm
STANDARD_DEVIATION 8.95 • n=5 Participants
|
|
Weight
|
85.11 kg
STANDARD_DEVIATION 15.46 • n=5 Participants
|
81.54 kg
STANDARD_DEVIATION 17.25 • n=7 Participants
|
83.31 kg
STANDARD_DEVIATION 16.42 • n=5 Participants
|
|
BMI
|
28.15 kg/m^2
STANDARD_DEVIATION 5.277 • n=5 Participants
|
27.64 kg/m^2
STANDARD_DEVIATION 5.100 • n=7 Participants
|
27.89 kg/m^2
STANDARD_DEVIATION 5.175 • n=5 Participants
|
|
ECOG status
0
|
44 participants
n=5 Participants
|
45 participants
n=7 Participants
|
89 participants
n=5 Participants
|
|
ECOG status
1
|
21 participants
n=5 Participants
|
21 participants
n=7 Participants
|
42 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: In week 3 of every second cycle (each cycle was 21 days) for all subjects enrolled, up to the end of cycle 6 (About 5 months after randomization)Population: ITT population consisted of all subjects randomised to treatment who received at least one dose of study medication, had a valid baseline measurement and who had returned for at least one visit post-baseline
The Proportion of Patients With Objective Response or Stable Disease (Non-progression Rate) after six treatment cycles
Outcome measures
| Measure |
Arm 1- PI-88 Plus Dacarbazine
n=65 Participants
PI-88 (muparfostat) 190 mg daily by subcutaneous injection and dacarbazine 1000 mg/m2 on day 1 of each 21 day cycle
PI-88 and dacarbazine: 190 mg daily by subcutaneous injection for PI-88 and 1000 mg/m2 on day 1 of each 21 day cycle by intravenous infusion
|
Arm 2- Dacarbazine Alone
n=65 Participants
dacarbazine 1000 mg/m2 on day 1 of every 21 day cycle by intravenous infusion
dacarbazine or DTIC: intravenous infusion 1000 mg/m2 on day 1 of every 21 day cycle
|
|---|---|---|
|
Non-progression Rate After Six Cycles
Non-progressed
|
13 Participants
|
18 Participants
|
|
Non-progression Rate After Six Cycles
Progressed
|
52 Participants
|
47 Participants
|
SECONDARY outcome
Timeframe: In week 3 of every second cycle (each cycle was 21 days) for all subjects enrolled in cycle 2 and cycle 4.Population: ITT population, consisted of all subjects randomised to treatment who received at least one dose of study medication, had a valid baseline measurement and who had returned for at least one visit post-baseline.
The Proportion of Patients With Objective Response or Stable Disease (Non-progression Rate) after 2 or 4 treatment cycles
Outcome measures
| Measure |
Arm 1- PI-88 Plus Dacarbazine
n=65 Participants
PI-88 (muparfostat) 190 mg daily by subcutaneous injection and dacarbazine 1000 mg/m2 on day 1 of each 21 day cycle
PI-88 and dacarbazine: 190 mg daily by subcutaneous injection for PI-88 and 1000 mg/m2 on day 1 of each 21 day cycle by intravenous infusion
|
Arm 2- Dacarbazine Alone
n=65 Participants
dacarbazine 1000 mg/m2 on day 1 of every 21 day cycle by intravenous infusion
dacarbazine or DTIC: intravenous infusion 1000 mg/m2 on day 1 of every 21 day cycle
|
|---|---|---|
|
Non-progression Rate
End of cycle 2_progressed
|
32 Participants
|
30 Participants
|
|
Non-progression Rate
End of cycle 4_Non-progressed
|
24 Participants
|
31 Participants
|
|
Non-progression Rate
End of cycle 2_Non-progressed
|
33 Participants
|
35 Participants
|
|
Non-progression Rate
End of cycle 4_progressed
|
41 Participants
|
33 Participants
|
SECONDARY outcome
Timeframe: At screening and in week 3 of every second cycle up to the end of cycle 6 and every third cycle after cycle 6 . Each cycle was 21 days.Assessed from date of randomization until the date of first documented progression, up to 50 months.Population: ITT population consisted of all subjects randomised to treatment who received at least one dose of study medication, had a valid baseline measurement and who had returned for at least one visit post-baseline
treatment was to continue until the subject experienced disease progression.
Outcome measures
| Measure |
Arm 1- PI-88 Plus Dacarbazine
n=65 Participants
PI-88 (muparfostat) 190 mg daily by subcutaneous injection and dacarbazine 1000 mg/m2 on day 1 of each 21 day cycle
PI-88 and dacarbazine: 190 mg daily by subcutaneous injection for PI-88 and 1000 mg/m2 on day 1 of each 21 day cycle by intravenous infusion
|
Arm 2- Dacarbazine Alone
n=65 Participants
dacarbazine 1000 mg/m2 on day 1 of every 21 day cycle by intravenous infusion
dacarbazine or DTIC: intravenous infusion 1000 mg/m2 on day 1 of every 21 day cycle
|
|---|---|---|
|
Time to Progression
|
66 days
Interval 43.0 to 134.0
|
82 days
Interval 43.0 to 187.0
|
SECONDARY outcome
Timeframe: At screening and in week 3 of every second cycle up to the end of cycle 6 and every third cycle after cycle 6. Each cycle was 21 days. Assessed from date of randomization until the date of first documented progression, up to 50 months.Population: ITT population consisted of all subjects randomised to treatment who received at least one dose of study medication, had a valid baseline measurement and who had returned for at least one visit post-baseline
time from commencement to radiological evidence of progression
Outcome measures
| Measure |
Arm 1- PI-88 Plus Dacarbazine
n=65 Participants
PI-88 (muparfostat) 190 mg daily by subcutaneous injection and dacarbazine 1000 mg/m2 on day 1 of each 21 day cycle
PI-88 and dacarbazine: 190 mg daily by subcutaneous injection for PI-88 and 1000 mg/m2 on day 1 of each 21 day cycle by intravenous infusion
|
Arm 2- Dacarbazine Alone
n=65 Participants
dacarbazine 1000 mg/m2 on day 1 of every 21 day cycle by intravenous infusion
dacarbazine or DTIC: intravenous infusion 1000 mg/m2 on day 1 of every 21 day cycle
|
|---|---|---|
|
Duration of Response
|
117.0 days
Standard Deviation 65.73
|
140.6 days
Standard Deviation 89.38
|
SECONDARY outcome
Timeframe: It was to assess time to death. The time frame is at least 6th month, 12th month and data was continuously collected till the end of the study, up to 50 months..Population: ITT population consisted of all subjects randomised to treatment who received at least one dose of study medication, had a valid baseline measurement and who had returned for at least one visit post-baseline
time to death and also at time-points 6 month and 12 months
Outcome measures
| Measure |
Arm 1- PI-88 Plus Dacarbazine
n=65 Participants
PI-88 (muparfostat) 190 mg daily by subcutaneous injection and dacarbazine 1000 mg/m2 on day 1 of each 21 day cycle
PI-88 and dacarbazine: 190 mg daily by subcutaneous injection for PI-88 and 1000 mg/m2 on day 1 of each 21 day cycle by intravenous infusion
|
Arm 2- Dacarbazine Alone
n=65 Participants
dacarbazine 1000 mg/m2 on day 1 of every 21 day cycle by intravenous infusion
dacarbazine or DTIC: intravenous infusion 1000 mg/m2 on day 1 of every 21 day cycle
|
|---|---|---|
|
Survival
|
304.00 days
Interval 224.0 to 366.0
|
416.00 days
Interval 304.0 to 476.0
|
Adverse Events
Arm 1- PI-88 Plus Dacarbazine
Serious events: 20 serious events
Other events: 65 other events
Deaths: 0 deaths
Arm 2- Dacarbazine Alone
Serious events: 13 serious events
Other events: 61 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Arm 1- PI-88 Plus Dacarbazine
n=65 participants at risk
PI-88 (muparfostat) 190 mg daily by subcutaneous injection and dacarbazine 1000 mg/m2 on day 1 of each 21 day cycle
PI-88 and dacarbazine: 190 mg daily by subcutaneous injection for PI-88 and 1000 mg/m2 on day 1 of each 21 day cycle by intravenous infusion
|
Arm 2- Dacarbazine Alone
n=66 participants at risk
dacarbazine 1000 mg/m2 on day 1 of every 21 day cycle by intravenous infusion
dacarbazine or DTIC: intravenous infusion 1000 mg/m2 on day 1 of every 21 day cycle
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
3.1%
2/65
|
0.00%
0/66
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/65
|
1.5%
1/66
|
|
Blood and lymphatic system disorders
Heparin-induced thrombocytopenia
|
1.5%
1/65
|
0.00%
0/66
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/65
|
1.5%
1/66
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
6.2%
4/65
|
0.00%
0/66
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/65
|
1.5%
1/66
|
|
Gastrointestinal disorders
Abdominal pain
|
1.5%
1/65
|
1.5%
1/66
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/65
|
1.5%
1/66
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
1.5%
1/65
|
1.5%
1/66
|
|
General disorders
Pain
|
1.5%
1/65
|
0.00%
0/66
|
|
General disorders
Pyrexia
|
1.5%
1/65
|
1.5%
1/66
|
|
Infections and infestations
Cellulitis
|
1.5%
1/65
|
0.00%
0/66
|
|
Infections and infestations
Lower respiratory tract infection
|
1.5%
1/65
|
1.5%
1/66
|
|
Infections and infestations
Pneumonia
|
0.00%
0/65
|
1.5%
1/66
|
|
Infections and infestations
Respiratory tract infection
|
1.5%
1/65
|
0.00%
0/66
|
|
Infections and infestations
Sepsis
|
0.00%
0/65
|
1.5%
1/66
|
|
Infections and infestations
Subcutaneous abscess
|
1.5%
1/65
|
0.00%
0/66
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/65
|
1.5%
1/66
|
|
Injury, poisoning and procedural complications
Overdose
|
1.5%
1/65
|
0.00%
0/66
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
1.5%
1/65
|
0.00%
0/66
|
|
Investigations
Antibody test positive
|
1.5%
1/65
|
0.00%
0/66
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.5%
1/65
|
0.00%
0/66
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
1.5%
1/65
|
0.00%
0/66
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion
|
1.5%
1/65
|
0.00%
0/66
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
0.00%
0/65
|
1.5%
1/66
|
|
Nervous system disorders
Cerebral haemorrhage
|
1.5%
1/65
|
0.00%
0/66
|
|
Nervous system disorders
Cerebral infarction
|
1.5%
1/65
|
0.00%
0/66
|
|
Nervous system disorders
Embolic stroke
|
1.5%
1/65
|
0.00%
0/66
|
|
Nervous system disorders
Headache
|
1.5%
1/65
|
1.5%
1/66
|
|
Nervous system disorders
Hemiparesis
|
0.00%
0/65
|
1.5%
1/66
|
|
Nervous system disorders
Loss of consciousness
|
0.00%
0/65
|
1.5%
1/66
|
|
Nervous system disorders
Syncope
|
1.5%
1/65
|
0.00%
0/66
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/65
|
1.5%
1/66
|
|
Renal and urinary disorders
Haemorrhage urinary tract
|
1.5%
1/65
|
0.00%
0/66
|
|
Renal and urinary disorders
Renal failure acute
|
1.5%
1/65
|
0.00%
0/66
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/65
|
1.5%
1/66
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
1.5%
1/65
|
0.00%
0/66
|
|
Skin and subcutaneous tissue disorders
discolouration
|
1.5%
1/65
|
0.00%
0/66
|
Other adverse events
| Measure |
Arm 1- PI-88 Plus Dacarbazine
n=65 participants at risk
PI-88 (muparfostat) 190 mg daily by subcutaneous injection and dacarbazine 1000 mg/m2 on day 1 of each 21 day cycle
PI-88 and dacarbazine: 190 mg daily by subcutaneous injection for PI-88 and 1000 mg/m2 on day 1 of each 21 day cycle by intravenous infusion
|
Arm 2- Dacarbazine Alone
n=66 participants at risk
dacarbazine 1000 mg/m2 on day 1 of every 21 day cycle by intravenous infusion
dacarbazine or DTIC: intravenous infusion 1000 mg/m2 on day 1 of every 21 day cycle
|
|---|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
30.8%
20/65
|
27.3%
18/66
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
23.1%
15/65
|
12.1%
8/66
|
|
Cardiac disorders
Palpitations
|
6.2%
4/65
|
1.5%
1/66
|
|
Eye disorders
Visual impairment
|
6.2%
4/65
|
0.00%
0/66
|
|
Gastrointestinal disorders
Abdominal pain
|
7.7%
5/65
|
13.6%
9/66
|
|
Gastrointestinal disorders
Constipation
|
38.5%
25/65
|
24.2%
16/66
|
|
Gastrointestinal disorders
Diarrhoea
|
21.5%
14/65
|
24.2%
16/66
|
|
Gastrointestinal disorders
Dry mouth
|
6.2%
4/65
|
1.5%
1/66
|
|
Gastrointestinal disorders
Dyspepsia
|
10.8%
7/65
|
10.6%
7/66
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
7.7%
5/65
|
6.1%
4/66
|
|
Gastrointestinal disorders
Nausea
|
53.8%
35/65
|
59.1%
39/66
|
|
Gastrointestinal disorders
Vomiting
|
21.5%
14/65
|
19.7%
13/66
|
|
General disorders
Chest pain
|
10.8%
7/65
|
12.1%
8/66
|
|
General disorders
Chills
|
4.6%
3/65
|
10.6%
7/66
|
|
General disorders
Fatigue
|
60.0%
39/65
|
59.1%
39/66
|
|
General disorders
Infusion site pain
|
6.2%
4/65
|
12.1%
8/66
|
|
General disorders
Injection site haematoma
|
46.2%
30/65
|
1.5%
1/66
|
|
General disorders
Inject site pain
|
21.5%
14/65
|
3.0%
2/66
|
|
General disorders
Injection site reaction
|
18.5%
12/65
|
0.00%
0/66
|
|
General disorders
Oedema peripheral
|
9.2%
6/65
|
3.0%
2/66
|
|
General disorders
Pain
|
6.2%
4/65
|
7.6%
5/66
|
|
General disorders
Pyrexia
|
4.6%
3/65
|
12.1%
8/66
|
|
Infections and infestations
Lower respiratory track infection
|
3.1%
2/65
|
7.6%
5/66
|
|
Infections and infestations
Nasopharyngitis
|
4.6%
3/65
|
10.6%
7/66
|
|
Infections and infestations
Upper respiratory tract infection
|
6.2%
4/65
|
9.1%
6/66
|
|
Injury, poisoning and procedural complications
Contusion
|
20.0%
13/65
|
7.6%
5/66
|
|
Investigations
Alanine aminotransferase increased
|
9.2%
6/65
|
0.00%
0/66
|
|
Investigations
Platelet count decreased
|
6.2%
4/65
|
0.00%
0/66
|
|
Investigations
Weight decreased
|
6.2%
4/65
|
4.5%
3/66
|
|
Metabolism and nutrition disorders
Decreased appetite
|
21.5%
14/65
|
22.7%
15/66
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
12.3%
8/65
|
10.6%
7/66
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.3%
8/65
|
15.2%
10/66
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
1.5%
1/65
|
7.6%
5/66
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
12.3%
8/65
|
3.0%
2/66
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
4.6%
3/65
|
16.7%
11/66
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
10.8%
7/65
|
1.5%
1/66
|
|
Nervous system disorders
Burning sensation
|
7.7%
5/65
|
0.00%
0/66
|
|
Nervous system disorders
Dizziness
|
21.5%
14/65
|
19.7%
13/66
|
|
Nervous system disorders
Dysgeusia
|
6.2%
4/65
|
6.1%
4/66
|
|
Nervous system disorders
Headache
|
16.9%
11/65
|
24.2%
16/66
|
|
Nervous system disorders
Lethargy
|
10.8%
7/65
|
4.5%
3/66
|
|
Psychiatric disorders
Anxiety
|
6.2%
4/65
|
3.0%
2/66
|
|
Psychiatric disorders
Depression
|
3.1%
2/65
|
10.6%
7/66
|
|
Psychiatric disorders
Insomnia
|
24.6%
16/65
|
21.2%
14/66
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
21.5%
14/65
|
15.2%
10/66
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
16.9%
11/65
|
12.1%
8/66
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
9.2%
6/65
|
4.5%
3/66
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
1.5%
1/65
|
6.1%
4/66
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
10.8%
7/65
|
3.0%
2/66
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
7.7%
5/65
|
6.1%
4/66
|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
4.6%
3/65
|
13.6%
9/66
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.8%
7/65
|
4.5%
3/66
|
|
Skin and subcutaneous tissue disorders
Rash
|
10.8%
7/65
|
9.1%
6/66
|
|
Vascular disorders
Flushing
|
9.2%
6/65
|
4.5%
3/66
|
Additional Information
Director of Regulatory Affairs and Clinical Development
Progen Pharmaceuticals Ltd
Phone: +61 (0)7 38423333
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place