Ph 2/3 Study in Subjects With MPM to Assess ADI-PEG 20 With Pemetrexed and Cisplatin

Mesothelioma Clinical Trial

— ATOMIC  

Official 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02709512
• Other study ID #: POLARIS2015-003
• Status: Completed
• Phase: Phase 2/Phase 3
• 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
• 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.

Related Conditions & MeSH terms

• Mesothelioma
• Mesothelioma, Malignant

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