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

September 9, 2023 updated by: Polaris Group

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

249

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Chris O'Brien Lifehouse
      • Tweed Heads, New South Wales, Australia, 2486
        • Tweed Hospital (NNSW LHD)
    • Queensland
      • Woolloongabba, Queensland, Australia, 4102
        • Princess Alexandria Hospital and Health Services
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
        • Southern Adelaide Local Health Network, Inc.
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Austin Health
    • Western Australia
      • Perth, Western Australia, Australia, 6009
        • Sir Charles Gairdner Hospital
  • Italy
      • Milan, Italy, 20133
        • Fondazione IRCCS - Istituto Nazionale dei Tumori Milano
      • Parma, Italy, 43126
        • Azienda Ospedaliero Universitaria di Parma
      • Pisa, Italy, 56124
        • Azienda Ospedaliero Universitaria Pisana
    • AL
      • Alessandria, AL, Italy, 15121
        • SS. Antonio e Biagio e Cesare Arrigo Hospital
    • BG
      • Bergamo, BG, Italy, 24125
        • Humanitas Gavazzeni
    • GE
      • Genova, GE, Italy, 16149
        • Ospedale Villa Scassi
    • MB
      • Monza, MB, Italy, 20900
        • Azienda Ospedaliera San Gerardo - Monza, Chirurgia Toracica
    • MI
      • Milano, MI, Italy, 20141
        • European Institute of Oncology
    • PV
      • Pavia, PV, Italy, 27100
        • Fondazione IRCCS Policlinico San Matteo
  • Taiwan
      • Kaohsiung, Taiwan, 807
        • Kaohsiung Medical University Chung-Ho Memorial Hospital
      • Kaohsiung, Taiwan, 83301
        • Chang Gung Medical Foundation Kaohsiung
      • Taichung, Taiwan, 407
        • Taichung Veterans General Hospital
      • Taipei, Taiwan, 10002
        • National Taiwan University Hospital
      • Taipei, Taiwan, 112
        • Taipei Veterans General Hospital
      • Taoyuan, Taiwan, 33305
        • Chang Gung Memorial Foundation LinKou Branch
  • United Kingdom
      • Cardiff, United Kingdom, CF14 2TL
        • Velindre Cancer Centre
      • Edinburgh, United Kingdom, EH4 2XU
        • Edinburgh Cancer Centre
      • Glasgow, United Kingdom, G12 0YN
        • Beatson West Of Scotland Cancer Centre
      • Leeds, United Kingdom, LS9 7TF
        • St James's University Hospital
      • London, United Kingdom, EC1A 7BE
        • St Bartholomew's Hospital
      • Manchester, United Kingdom, M23 9LT
        • University Hospital of South Manchester
    • Cambridgeshire
      • Cambridge, Cambridgeshire, United Kingdom, CB20QQ
        • Addenbrooke's Hospital
    • Devon
      • Plymouth, Devon, United Kingdom, PL6 8DH
        • Plymouth Hospitals (Derriford Hospital)
    • England
      • London, England, United Kingdom, EC1M 6BQ
        • Centre for Experimental Cancer Medicine (CECM)
    • Hampshire
      • Southampton, Hampshire, United Kingdom, SO16 6YD
        • Southampton General Hospital
    • Leicestershire
      • Leicester, Leicestershire, United Kingdom, LE1 5WW
        • University Hospitals Leicester
    • North Lincolnshire
      • Scunthorpe, North Lincolnshire, United Kingdom, DN15 7BH
        • Scunthorpe General Hospital
    • Northumberland
      • Ashington, Northumberland, United Kingdom, NE63 9JJ
        • Wansbeck General Hospital
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX3 7LE
        • Oxford Cancer and Haematology Centre, The Churchill Hospital
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic
    • California
      • Los Angeles, California, United States, 90095
        • UCLA Hematology & Oncology - Santa Monica
      • San Francisco, California, United States, 94115
        • University of California San Francisco Helen Diller Comprehensive Cancer Center
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center & Research Institute
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland, Marlene & Stewart Greenebaum Comprehensive Cancer Center
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Drug: ADI-PEG 20 plus Pem Platinum
Investigational Drug in combination approved standard of care treatment for this indication
Other Names:
  • Cisplatin
  • Carboplatin
  • Pemetrexed
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
Other: Placebo plus Pem Platinum
Placebo in combination approved standard of care treatment for this indication
Other Names:
  • Cisplatin
  • Carboplatin
  • Pemetrexed

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response Rate
Time Frame: approximately 18 months

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
Overall Survival Phase 3 Interim Analysis
Time Frame: Approximately 18 months

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
Overall Survival
Time Frame: 18 months

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 α = 0.04999 (two-sided).
18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: approximately 18 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Polaris Group

Investigators

  • Study Director: John S Bomalaski, MD, Polaris Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2017

Primary Completion (Actual)

August 15, 2022

Study Completion (Actual)

August 15, 2022

Study Registration Dates

First Submitted

March 5, 2016

First Submitted That Met QC Criteria

March 10, 2016

First Posted (Estimated)

March 16, 2016

Study Record Updates

Last Update Posted (Actual)

October 4, 2023

Last Update Submitted That Met QC Criteria

September 9, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • POLARIS2015-003

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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