Clinical Trial Results:
RANDOMIZED, DOUBLE-BLIND, PHASE 2/3 STUDY IN SUBJECTS WITH MALIGNANT PLEURAL MESOTHELIOMA TO ASSESS ADI-PEG 20 WITH PEMETREXED AND CISPLATIN (ATOMIC-MESO PHASE 2/3 STUDY)
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Summary
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EudraCT number |
2015-004281-28 |
Trial protocol |
GB IT |
Global end of trial date |
18 Aug 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Dec 2025
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First version publication date |
19 Dec 2025
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Other versions |
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Summary report(s) |
Clinical Study Report - Polaris2015-003 subject-disposition demographic-data End Points Adverse Events More Information - Protocol and Protocol Amendments |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
POLARIS2015-003
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02709512 | ||
WHO universal trial number (UTN) |
U1111-1170-6516 | ||
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Sponsors
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Sponsor organisation name |
Polaris Group
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Sponsor organisation address |
9990 Mesa Rim Road, Suite 110, San Diego, CA, United States, 92121
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Public contact |
Mirla Langlois, Designe Rx Europe Limited, 1 858-452-6688, mlanglois@polarispharma.com
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Scientific contact |
Mirla Langlois, Designe Rx Europe Limited, 1 858-452-6688, mlanglois@polarispharma.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
14 Sep 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 Aug 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Aug 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Determine efficacy as determined by RR, measured by modified RECIST criteria for unresectable MPM and RECIST 1.1 criteria (phase 2 portion) and OS (phase 3 portion)
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Protection of trial subjects |
Key Protections for Participants:
Informed Consent: Participants voluntarily agreed to participate after being fully informed about the trial's risks, benefits, and procedures.
Right to Withdraw: Participants could change their minds and withdraw from a trial at any time without penalty.
Privacy and Confidentiality: Personal and health information was kept private and secure, with only authorized personnel having access to the data.
Independent Data Safety Monitoring Board had oversight and reviewed data to ensure safety of participants
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Background therapy |
Pemetrexed is a folate analog metabolic inhibitor Cisplatin is a heavy metal compound containing platinum Carboplatin is a platinum-based n ankylating agent Pemetrexed (500 mg/m2), Cisplatin (75 mg/m2), Carboplatin (AUC 5) | ||
Evidence for comparator |
This is a randomized, double-blind, multi-center, phase 2/3 trial of ADI-PEG 20 in combination with pemetrexed and cisplatin or Carboplatin in subjects with unresectable MPM of sarcomatoid or biphasic histologies. Placebo comparator was used. | ||
Actual start date of recruitment |
01 Aug 2017
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy | ||
Long term follow-up duration |
12 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Australia: 18
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Country: Number of subjects enrolled |
Italy: 30
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Country: Number of subjects enrolled |
Taiwan: 4
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Country: Number of subjects enrolled |
United Kingdom: 144
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Country: Number of subjects enrolled |
United States: 53
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Worldwide total number of subjects |
249
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EEA total number of subjects |
30
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
58
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From 65 to 84 years |
191
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruitment started in 01st August 2017 and ended 15th August 2021. The planned enrollment period was 36 months. Enrollment took place in US, UK, Australia, Italy and Taiwan. | |||||||||
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Pre-assignment
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Screening details |
Recording age, gender, race, ethnicity (i.e. demographics). Taking a medical history, noting any medications you may be taking and if you have had any side effects from them. Completing a physical exam. Performance status assessment, to see how well you are able to perform your normal daily activities. Blood sampling for routine laboratory test. | |||||||||
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Period 1
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Period 1 title |
Treatment and Follow-up Period (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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ADI-PEG 20 | |||||||||
Arm description |
Active Arm | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Pegargiminase
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Investigational medicinal product code |
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Other name |
ADI-PEG 20
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
36 mg/m2 weekly, Intramuscularly
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Arm title
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Placebo | |||||||||
Arm description |
Placebo arm | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
36 mg/m2 equivalent Placebo weekly, Intramuscularly
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Baseline characteristics reporting groups
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Reporting group title |
ADI-PEG 20
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Reporting group description |
Active Arm | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo arm | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
ADI PEM Platinum
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Active Group
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Subject analysis set title |
ADI PEM Platinum
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Placebo Group
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End points reporting groups
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Reporting group title |
ADI-PEG 20
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Reporting group description |
Active Arm | ||
Reporting group title |
Placebo
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Reporting group description |
Placebo arm | ||
Subject analysis set title |
ADI PEM Platinum
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Active Group
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Subject analysis set title |
ADI PEM Platinum
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Placebo Group
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End point title |
OS | ||||||||||||
End point description |
Overall Survival
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End point type |
Primary
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End point timeframe |
36 months
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Statistical analysis title |
Overall Survival | ||||||||||||
Comparison groups |
ADI-PEG 20 v Placebo
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Number of subjects included in analysis |
249
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Analysis specification |
Pre-specified
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Analysis type |
equivalence [1] | ||||||||||||
P-value |
= 0.0234 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Cox proportional hazard | ||||||||||||
Point estimate |
0.71
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.55 | ||||||||||||
upper limit |
0.93 | ||||||||||||
Variability estimate |
Standard deviation
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Dispersion value |
0.5
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| Notes [1] - 125 subjects in the ADI-PEG 20 group |
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End point title |
PFS | ||||||||||||
End point description |
Progression Free Survival
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End point type |
Secondary
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End point timeframe |
36 months
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Statistical analysis title |
Progression Free Survival | ||||||||||||
Comparison groups |
ADI-PEG 20 v Placebo
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Number of subjects included in analysis |
249
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Analysis specification |
Pre-specified
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Analysis type |
equivalence [2] | ||||||||||||
P-value |
= 0.0193 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Cox proportional hazard | ||||||||||||
Point estimate |
0.5
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.46 | ||||||||||||
upper limit |
0.9 | ||||||||||||
Variability estimate |
Standard deviation
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Dispersion value |
0.65
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| Notes [2] - 125 subjects in the ADI-PEG 20 group |
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Adverse events information
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Timeframe for reporting adverse events |
After the first dose and until 30 days after the last dose.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.1
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Reporting groups
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Reporting group title |
ADIPemPlatinum
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PlaceboPemPlatinum
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Notes [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [16] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [17] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [18] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [19] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [20] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [21] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [22] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [23] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [24] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [25] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [26] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [27] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [28] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [29] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [30] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [31] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [32] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [33] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [34] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [35] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [36] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [37] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [38] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [39] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [40] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [41] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [42] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [43] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [44] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [45] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [46] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [47] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [48] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [49] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [50] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [51] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [52] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [53] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [54] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [55] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [56] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [57] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [58] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [59] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [60] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [61] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [62] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [63] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [64] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [65] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [66] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [67] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [68] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [69] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [70] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [71] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [72] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [73] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [74] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [75] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [76] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [77] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) |
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Notes [78] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [79] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [80] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [81] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [82] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [83] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [84] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [85] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [86] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [87] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [88] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [89] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [90] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [91] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) [92] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects exposed to this adverse event is equal to the total number of subjects exposed to this adverse event. This discrepancy is due to the number of subjects for each reporting group (ADI and Placebo) |
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Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
12 Nov 2019 |
1. Removed “with Low Argininosuccinate Synthetase 1 Esxpression” from the protocol title.
Rationale: ASS1 testing will no longer be required or conducted as ASS1 expression level is no longer considered important when ADI-PEG 20 is combined with chemotherapy.
2. Removed requirement for tumor samples for ASS1 testing as an eligibility criterion and other studyspecific
sections and references related to tumor sample collection and ASS1 testing.
Rationale: ASS1 deficiency is no longer considered important when ADI-PEG 20 is combined with
chemotherapy.
3. Removed response rate (RR), duration of response (DOR) and disease control rate (DCR) as secondary
efficacy endpoints for the phase 3 portion
Rationale: RR will only be analyzed once at the first interim analysis at the end of phase 2 portion to support
accelerated approval and will not be analyzed again at the end of phase 3. Progression free survival (PFS) is
the key secondary efficacy endpoint for the phase 3.
4. Removed requirement for confirmation of measurable disease by blinded independent central review
(BICR)
Rationale: Sites are fully capable of determining measurable disease (to-date, only 2% were found ineligible
and 1% as borderline cases by BICR). This would reduce logistic issues at sites (potential delay in subject
enrollment) and vendor management cost.
5. Removed requirement for confirmational scans 4 weeks after the scheduled scans showing tumor response
(PR and CR)
Rationale: The conformational scan is unnecessary for a randomized, double-blind, controlled study with
BICR and with 6-week intervals for tumor scans scheduled for all subjects on study. This would also reduce
complexity of scheduling for the sites.
6. Removed requirement for BICR to determine PFS in phase 3 portion
Rationale: Simplification for logistics management and reduction of vendor management cost.
|
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
|||
| http://www.ncbi.nlm.nih.gov/pubmed/38358753 http://www.ncbi.nlm.nih.gov/pubmed/34589965 http://www.ncbi.nlm.nih.gov/pubmed/33358660 |
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