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Ph 2/3 Study in Subjects With MPM w/Low ASS 1 Expression to Assess ADI-PEG 20 With Pemetrexed and Cisplatin (ATOMIC)

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ClinicalTrials.gov Identifier: NCT02709512
Recruitment Status : Recruiting
First Posted : March 16, 2016
Last Update Posted : July 4, 2018
Sponsor:
Information provided by (Responsible Party):
Polaris Group

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 with low argininosuccinate synthetase 1 expression. 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.

Condition or disease Intervention/treatment Phase
Mesothelioma Drug: ADI-PEG 20 plus Pem Cis Other: Placebo plus Pem Cis Phase 2 Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 386 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Randomized, Double-Blind, Phase 2/3 Study in Subjects With Malignant Pleural Mesothelioma With Low Argininosuccinate Synthetase 1 Expression to Assess ADI-PEG 20 With Pemetrexed and Cisplatin (ATOMIC-Meso Phase 2/3 Study)
Actual Study Start Date : August 1, 2017
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma

Arm Intervention/treatment
Experimental: Drug: ADI-PEG 20 plus Pem Cis

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

Drug: ADI-PEG 20 plus Pem Cis
Investigational Drug in combination approved standard of care treatment for this indication
Other Names:
  • Pemetrexed
  • Cisplatin

Placebo Comparator: Drug: Placebo plus Pem Cis

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

Other: Placebo plus Pem Cis
Placebo in combination approved standard of care treatment for this indication
Other Names:
  • Pemetrexed
  • Cisplatin




Primary Outcome Measures :
  1. Response Rate [ Time Frame: approximately 18 months ]

Secondary Outcome Measures :
  1. Progression Free Survival [ Time Frame: approximately 18 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically proven advanced MPM of biphasic or sarcomatoid histology. Biphasic MPM is defined using the World Health Organization's international histological classification of tumors as containing an epithelial and a sarcomatoid component with each component comprising at least 10% of the tumor
  2. Naïve to prior chemotherapy or immunotherapy (i.e., this is a first-line systemic therapy study).
  3. MPM tumor sample for determination of ASS1 status. ASS1-deficiency is not required for study entry at study start, but tumor sample for ASS1 status is required. This study will employ an adaptive biomarker-driven design with an interim analysis to be conducted at the end of the phase 2 portion. The interim analysis will evaluate the treatment effect of ADI PEG 20 in combination with pemetrexed and cisplatin on overall survival (OS) in the overall population (biphasic and sarcomatoid histology patients) and pre-defined subpopulation of biomarker-positive patients (ASS1-deficient subpopulation). Thus ASS1 deficiency may be required for the phase 3 portion of the study, pending the interim analysis. ASS1-deficiency, demonstrated on tissue specimen (cytospin samples are not acceptable), will be defined in the laboratory manual. If archived tissue is not sufficient or not available, then tissue must be obtained by biopsy.
  4. Measurable disease as assessed by modified RECIST for MPM for thoracic disease (Appendix A) and RECIST 1.1 for extra-thoracic disease (Appendix B).
  5. ECOG performance status of 0 - 1 (Appendix C).
  6. Predicted life expectancy of at least 12 weeks.

Exclusion Criteria:

  1. Radiotherapy (except for palliative reasons) the previous two weeks before.
  2. Ongoing toxic manifestations of previous treatments.
  3. Symptomatic brain or spinal cord metastases (patients must be stable for > 1 month post radiotherapy or surgery).
  4. Major thoracic or abdominal surgery from which the patient has not yet recovered.
  5. Serious infection requiring treatment with intravenous antibiotics at the time of study entrance, or an infection requiring intravenous therapy within 7 days prior.
  6. Known to be serologically positive for human immunodeficiency virus (HIV). Testing to determine possible infection status is not required.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02709512


Contacts
Contact: Phuong Lee 858-452-6688 ext 188 plee@polarispharma.com

Locations
United States, Arizona
Mayo Clinic Recruiting
Phoenix, Arizona, United States, 85054
Contact: Helen Ross, MD         
United States, California
UCLA Hematology & Oncology - Santa Monica Recruiting
Los Angeles, California, United States, 90095
Contact: Olga Olvesky, MD         
University of California San Francisco Helen Diller Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
Contact: Thierry Jahan, MD         
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Scott Antonia, MD         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Hedy Kindler, MD         
United States, Maryland
University of Maryland, Marlene & Stewart Greenebaum Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Ken Miller, MD         
United States, Michigan
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
Contact: Igor Rybkin, MD PhD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Aaron Mansfield, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Marjorie Zauderer, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Anne S Tsao, M.D.         
Australia, New South Wales
Tweed Hospital (NNSW LHD) Recruiting
Tweed Heads, New South Wales, Australia, 2486
Contact: Ehtesham Abdi, Prof         
Australia, Queensland
Princess Alexandria Hospital and Health Services Recruiting
Woolloongabba, Queensland, Australia, 4102
Contact: Ken O'Byrne, Prof         
Australia, South Australia
Southern Adelaide Local Health Network, Inc. Recruiting
Bedford Park, South Australia, Australia, 5042
Contact: Christos Karapetis, Prof         
Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital Recruiting
Kaohsiung, Taiwan, 807
Contact: Inn-Wen Chong         
United Kingdom
Centre for Experimental Cancer Medicine (CECM) Recruiting
London, England, United Kingdom, EC1M 6BQ
Contact: Peter Szlosarek, M.D. PhD         
Sponsors and Collaborators
Polaris Group
Investigators
Study Director: John S Bomalaski, MD Polaris

Responsible Party: Polaris Group
ClinicalTrials.gov Identifier: NCT02709512     History of Changes
Other Study ID Numbers: POLARIS2015-003
First Posted: March 16, 2016    Key Record Dates
Last Update Posted: July 4, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Polaris Group:
Malignant Pleural Mesothelioma with Low Argininosuccinate Synthetase 1 Expression

Additional relevant MeSH terms:
Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Cisplatin
Pemetrexed
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors