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

NCT ID: NCT02709512

Last Updated: 2023-10-04

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

249 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-08-01

Study Completion Date

2022-08-15

Brief Summary

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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.

Detailed Description

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Conditions

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Mesothelioma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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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

Group Type EXPERIMENTAL

ADI-PEG 20 plus Pem Platinum

Intervention Type DRUG

Investigational Drug in combination approved standard of care treatment for this indication

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

Group Type PLACEBO_COMPARATOR

Placebo plus Pem Platinum

Intervention Type OTHER

Placebo in combination approved standard of care treatment for this indication

Interventions

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ADI-PEG 20 plus Pem Platinum

Investigational Drug in combination approved standard of care treatment for this indication

Intervention Type DRUG

Placebo plus Pem Platinum

Placebo in combination approved standard of care treatment for this indication

Intervention Type OTHER

Other Intervention Names

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Pemetrexed Cisplatin Carboplatin Pemetrexed Cisplatin Carboplatin

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Polaris Group

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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John S Bomalaski, MD

Role: STUDY_DIRECTOR

Polaris Group

Locations

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Mayo Clinic

Phoenix, Arizona, United States

Site Status

UCLA Hematology & Oncology - Santa Monica

Los Angeles, California, United States

Site Status

University of California San Francisco Helen Diller Comprehensive Cancer Center

San Francisco, California, United States

Site Status

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

University of Maryland, Marlene & Stewart Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

Site Status

Tweed Hospital (NNSW LHD)

Tweed Heads, New South Wales, Australia

Site Status

Princess Alexandria Hospital and Health Services

Woolloongabba, Queensland, Australia

Site Status

Southern Adelaide Local Health Network, Inc.

Bedford Park, South Australia, Australia

Site Status

Austin Health

Heidelberg, Victoria, Australia

Site Status

Sir Charles Gairdner Hospital

Perth, Western Australia, Australia

Site Status

SS. Antonio e Biagio e Cesare Arrigo Hospital

Alessandria, AL, Italy

Site Status

Humanitas Gavazzeni

Bergamo, BG, Italy

Site Status

Ospedale Villa Scassi

Genova, GE, Italy

Site Status

Azienda Ospedaliera San Gerardo - Monza, Chirurgia Toracica

Monza, MB, Italy

Site Status

European Institute of Oncology

Milan, MI, Italy

Site Status

Fondazione IRCCS Policlinico San Matteo

Pavia, PV, Italy

Site Status

Fondazione IRCCS - Istituto Nazionale dei Tumori Milano

Milan, , Italy

Site Status

Azienda Ospedaliero Universitaria di Parma

Parma, , Italy

Site Status

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Site Status

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

Chang Gung Medical Foundation Kaohsiung

Kaohsiung City, , Taiwan

Site Status

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Chang Gung Memorial Foundation LinKou Branch

Taoyuan District, , Taiwan

Site Status

Addenbrooke's Hospital

Cambridge, Cambridgeshire, United Kingdom

Site Status

Plymouth Hospitals (Derriford Hospital)

Plymouth, Devon, United Kingdom

Site Status

Centre for Experimental Cancer Medicine (CECM)

London, England, United Kingdom

Site Status

Southampton General Hospital

Southampton, Hampshire, United Kingdom

Site Status

University Hospitals Leicester

Leicester, Leicestershire, United Kingdom

Site Status

Scunthorpe General Hospital

Scunthorpe, North Lincolnshire, United Kingdom

Site Status

Wansbeck General Hospital

Ashington, Northumberland, United Kingdom

Site Status

Oxford Cancer and Haematology Centre, The Churchill Hospital

Oxford, Oxfordshire, United Kingdom

Site Status

Velindre Cancer Centre

Cardiff, , United Kingdom

Site Status

Edinburgh Cancer Centre

Edinburgh, , United Kingdom

Site Status

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status

St James's University Hospital

Leeds, , United Kingdom

Site Status

St Bartholomew's Hospital

London, , United Kingdom

Site Status

University Hospital of South Manchester

Manchester, , United Kingdom

Site Status

Countries

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United States Australia Italy Taiwan United Kingdom

References

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Szlosarek PW, Creelan BC, Sarkodie T, Nolan L, Taylor P, Olevsky O, Grosso F, Cortinovis D, Chitnis M, Roy A, Gilligan D, Kindler H, Papadatos-Pastos D, Ceresoli GL, Mansfield AS, Tsao A, O'Byrne KJ, Nowak AK, Steele J, Sheaff M, Shiu CF, Kuo CL, Johnston A, Bomalaski J, Zauderer MG, Fennell DA; ATOMIC-Meso Study Group. Pegargiminase Plus First-Line Chemotherapy in Patients With Nonepithelioid Pleural Mesothelioma: The ATOMIC-Meso Randomized Clinical Trial. JAMA Oncol. 2024 Apr 1;10(4):475-483. doi: 10.1001/jamaoncol.2023.6789.

Reference Type DERIVED
PMID: 38358753 (View on PubMed)

Szlosarek PW, Phillips MM, Pavlyk I, Steele J, Shamash J, Spicer J, Kumar S, Pacey S, Feng X, Johnston A, Bomalaski J, Moir G, Lau K, Ellis S, Sheaff M. Expansion Phase 1 Study of Pegargiminase Plus Pemetrexed and Cisplatin in Patients With Argininosuccinate Synthetase 1-Deficient Mesothelioma: Safety, Efficacy, and Resistance Mechanisms. JTO Clin Res Rep. 2020 Sep 3;1(4):100093. doi: 10.1016/j.jtocrr.2020.100093. eCollection 2020 Nov.

Reference Type DERIVED
PMID: 34589965 (View on PubMed)

Uprety D. CheckMate 743: A Glimmer of Hope for Malignant Pleural Mesothelioma. Clin Lung Cancer. 2021 Mar;22(2):71-73. doi: 10.1016/j.cllc.2020.11.009. Epub 2020 Dec 2. No abstract available.

Reference Type DERIVED
PMID: 33358660 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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POLARIS2015-003

Identifier Type: -

Identifier Source: org_study_id

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