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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02709512
Registration number
NCT02709512
Ethics application status
Date submitted
5/03/2016
Date registered
16/03/2016
Date last updated
4/10/2023
Titles & IDs
Public title
Ph 2/3 Study in Subjects With MPM to Assess ADI-PEG 20 With Pemetrexed and Cisplatin
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Scientific title
Randomized, Double-Blind, Phase 2/3 Study in Subjects With Malignant Pleural Mesotheliomato Assess ADI-PEG 20 With Pemetrexed and Cisplatin (ATOMIC-Meso Phase 2/3 Study)
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Secondary ID [1]
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POLARIS2015-003
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Universal Trial Number (UTN)
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Trial acronym
ATOMIC
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Mesothelioma
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Condition category
Condition code
Cancer
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Lung - Mesothelioma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - ADI-PEG 20 plus Pem Platinum
Other interventions - Placebo plus Pem Platinum
Experimental: Drug: ADI-PEG 20 plus Pem Platinum - Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) Duration : Course of Study
In Combination With:
Pemetrexed Dose: 500 mg/m2 every 3 weeks Route of Administration: Intravenous Cisplatin Dose: 75 mg/m2 every 3 weeks Route of Administration: Intravenous Carboplatin Dose: AUC 5 mg/mL/min every 3 weeks Route of Administration: Intravenous
ADI-PEG 20 plus Pem Platinum: Investigational Drug in combination approved standard of care treatment for this indication
Placebo Comparator: Drug: Placebo plus Pem Platinum - Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) Duration : Course of Study
In Combination With:
Pemetrexed Dose: 500 mg/m2 every 3 weeks Route of Administration: Intravenous Cisplatin Dose: 75 mg/m2 every 3 weeks Carboplatin Dose: AUC 5 mg/mL/min every 3 weeks Route of Administration: Intravenous
Placebo plus Pem Platinum: Placebo in combination approved standard of care treatment for this indication
Treatment: Drugs: ADI-PEG 20 plus Pem Platinum
Investigational Drug in combination approved standard of care treatment for this indication
Other interventions: Placebo plus Pem Platinum
Placebo in combination approved standard of care treatment for this indication
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Intervention code [1]
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Treatment: Drugs
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Intervention code [2]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Response Rate
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Assessment method [1]
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Objective Response Rate is calculated as the proportion of subjects whose best tumor response from all post-baseline tumor assessments is complete response (CR) or partial response (PR). The best tumor response is the best response recorded from the start of the treatment until the end of treatment taking into account any requirement for confirmation.
To test Objective Response Rate significance, a Relative Risk Ratio (ADI-PEG 20 / Placebo) was calculated as the common relative risk of having a response (CR or PR) based on the Mantel-Haenszel estimator controlling for tumor histology (biphasic versus sarcomatoid).
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Timepoint [1]
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approximately 18 months
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Primary outcome [2]
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Overall Survival Phase 3 Interim Analysis
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Assessment method [2]
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The primary analysis of OS Phase 3 was performed at the interim analysis. This was performed once 50% of the planned OS events for phase 3 have occurred (ie, 169 of the 338 planned OS events). This interim analysis will evaluate OS in the ITT population in an unblinded manner. The OS data at the second interim analysis will be analyzed to support the following decisions:
Futility stopping: Terminate the study due to futility at the interim analysis. Sample size re-estimation: Increase the target number of OS events after the second interim analysis.. The treatment effect on OS will be evaluated using the stratified log-rank test (stratified by tumor histology).
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Timepoint [2]
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Approximately 18 months
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Primary outcome [3]
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Overall Survival
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Assessment method [3]
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Overall survival is defined as the time from randomization until death. In the event that no death was documented prior to study termination or analysis cutoff, OS was censored at the last known date the subject was known to be alive, either through completion of on-study visits or through survival follow-up contact.
The treatment effect on OS was evaluated using the stratified log-rank test (stratified by tumor histology).
The Kaplan-Meier curves were also plotted. A Cox proportional hazard model with an adjustment for tumor histology (biphasic vs sarcomatoid) was used to compute the estimated hazard ratio and two-sided 95% CI. The treatment effect on OS was evaluated using the stratified log-rank test (stratified by tumor histology). The significance level to be used in the OS analysis at the final analysis was based on a = 0.04999 (two-sided).
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Timepoint [3]
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18 months
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Secondary outcome [1]
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Progression Free Survival
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Assessment method [1]
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The key secondary endpoint for the phase 3 portion is PFS, which will be analyzed only if the analysis of OS is statistically significant at the final analysis, with alpha level of 0.05 (two-sided) using the same statistical methodologies as applied to OS.
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Timepoint [1]
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approximately 18 months
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Eligibility
Key inclusion criteria
- Histologically proven unresectable MPM of biphasic or sarcomatoid histology
- Naïve to chemotherapy or immunotherapy
- ECOG PS 0-1
- Expected survival of at least 3 months
- Age 18 years or over (there is no upper age limit)
- Measurable disease by modified RECIST criteria for MPM for local pleural disease and
RECIST 1.1 criteria for metastatic lesions
- Written (signed and dated) informed consent and must be capable of co-operating with
treatment and follow up
- Adequate hematologic, hepatic, and renal function
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- Radiotherapy (except for palliative reasons) in the previous two weeks before study
treatment
- History of unstable cardiac disease
- Ongoing toxic manifestations of previous treatments
- Symptomatic brain or spinal cord metastases (patients must be stable for > 1 month
post radiotherapy or surgery)
- Major thoracic or abdominal surgery from which the patient has not yet recovered.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2/Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/08/2017
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
15/08/2022
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Sample size
Target
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Accrual to date
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Final
249
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
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Recruitment hospital [1]
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Chris O'Brien Lifehouse - Camperdown
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Tweed Hospital (NNSW LHD) - Tweed Heads
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Princess Alexandria Hospital and Health Services - Woolloongabba
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Southern Adelaide Local Health Network, Inc. - Bedford Park
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Austin Health - Heidelberg
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Sir Charles Gairdner Hospital - Perth
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Recruitment postcode(s) [1]
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2050 - Camperdown
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Recruitment postcode(s) [2]
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2486 - Tweed Heads
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Recruitment postcode(s) [3]
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4102 - Woolloongabba
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Recruitment postcode(s) [4]
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5042 - Bedford Park
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Recruitment postcode(s) [5]
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3084 - Heidelberg
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Recruitment postcode(s) [6]
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6009 - Perth
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Recruitment outside Australia
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Arizona
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California
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AL
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Manchester
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Polaris Group
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Address
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Ethics approval
Ethics application status
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Summary
Brief summary
This is a study of ADI-PEG 20 (pegylated arginine deiminase), an arginine degrading enzyme
versus placebo in patients with malignant pleural mesothelioma. Malignant pleural
mesothelioma have been found to require arginine, an amino acid. Thus the hypothesis is that
by restricting arginine with ADI-PEG 20, the malignant pleural mesothelioma cells will starve
and die.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02709512
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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John S Bomalaski, MD
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Address
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Polaris Group
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02709512
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