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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02709512
Other study ID # POLARIS2015-003
Secondary ID
Status Completed
Phase Phase 2/Phase 3
First received
Last updated
Start date August 1, 2017
Est. completion date August 15, 2022

Study information

Verified date August 2023
Source Polaris Group
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 249
Est. completion date August 15, 2022
Est. primary completion date August 15, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
ADI-PEG 20 plus Pem Platinum
Investigational Drug in combination approved standard of care treatment for this indication
Other:
Placebo plus Pem Platinum
Placebo in combination approved standard of care treatment for this indication

Locations

Country Name City State
Australia Southern Adelaide Local Health Network, Inc. Bedford Park South Australia
Australia Chris O'Brien Lifehouse Camperdown New South Wales
Australia Austin Health Heidelberg Victoria
Australia Sir Charles Gairdner Hospital Perth Western Australia
Australia Tweed Hospital (NNSW LHD) Tweed Heads New South Wales
Australia Princess Alexandria Hospital and Health Services Woolloongabba Queensland
Italy SS. Antonio e Biagio e Cesare Arrigo Hospital Alessandria AL
Italy Humanitas Gavazzeni Bergamo BG
Italy Ospedale Villa Scassi Genova GE
Italy Fondazione IRCCS - Istituto Nazionale dei Tumori Milano Milan
Italy European Institute of Oncology Milano MI
Italy Azienda Ospedaliera San Gerardo - Monza, Chirurgia Toracica Monza MB
Italy Azienda Ospedaliero Universitaria di Parma Parma
Italy Fondazione IRCCS Policlinico San Matteo Pavia PV
Italy Azienda Ospedaliero Universitaria Pisana Pisa
Taiwan Chang Gung Medical Foundation Kaohsiung Kaohsiung
Taiwan Kaohsiung Medical University Chung-Ho Memorial Hospital Kaohsiung
Taiwan Taichung Veterans General Hospital Taichung
Taiwan National Taiwan University Hospital Taipei
Taiwan Taipei Veterans General Hospital Taipei
Taiwan Chang Gung Memorial Foundation LinKou Branch Taoyuan
United Kingdom Wansbeck General Hospital Ashington Northumberland
United Kingdom Addenbrooke's Hospital Cambridge Cambridgeshire
United Kingdom Velindre Cancer Centre Cardiff
United Kingdom Edinburgh Cancer Centre Edinburgh
United Kingdom Beatson West of Scotland Cancer Centre Glasgow
United Kingdom St James's University Hospital Leeds
United Kingdom University Hospitals Leicester Leicester Leicestershire
United Kingdom Centre for Experimental Cancer Medicine (CECM) London England
United Kingdom St Bartholomew's Hospital London
United Kingdom University Hospital of South Manchester Manchester
United Kingdom Oxford Cancer and Haematology Centre, The Churchill Hospital Oxford Oxfordshire
United Kingdom Plymouth Hospitals (Derriford Hospital) Plymouth Devon
United Kingdom Scunthorpe General Hospital Scunthorpe North Lincolnshire
United Kingdom Southampton General Hospital Southampton Hampshire
United States University of Maryland, Marlene & Stewart Greenebaum Comprehensive Cancer Center Baltimore Maryland
United States University of Chicago Chicago Illinois
United States Henry Ford Hospital Detroit Michigan
United States MD Anderson Cancer Center Houston Texas
United States UCLA Hematology & Oncology - Santa Monica Los Angeles California
United States Memorial Sloan Kettering Cancer Center New York New York
United States Mayo Clinic Phoenix Arizona
United States Mayo Clinic Rochester Minnesota
United States University of California San Francisco Helen Diller Comprehensive Cancer Center San Francisco California
United States H. Lee Moffitt Cancer Center & Research Institute Tampa Florida

Sponsors (1)

Lead Sponsor Collaborator
Polaris Group

Countries where clinical trial is conducted

United States,  Australia,  Italy,  Taiwan,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Response Rate 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).
approximately 18 months
Primary Overall Survival Phase 3 Interim Analysis 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).
Approximately 18 months
Primary Overall Survival 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).
18 months
Secondary Progression Free Survival 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. approximately 18 months
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