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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 : September 19, 2019
Sponsor:
Information provided by (Responsible Party):
Polaris Group

Tracking Information
First Submitted Date  ICMJE March 5, 2016
First Posted Date  ICMJE March 16, 2016
Last Update Posted Date September 19, 2019
Actual Study Start Date  ICMJE August 1, 2017
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 10, 2016)
Response Rate [ Time Frame: approximately 18 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02709512 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2016)
Progression Free Survival [ Time Frame: approximately 18 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ph 2/3 Study in Subjects With MPM w/Low ASS 1 Expression to Assess ADI-PEG 20 With Pemetrexed and Cisplatin
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Mesothelioma
Intervention  ICMJE
  • Drug: ADI-PEG 20 plus Pem Cis
    Investigational Drug in combination approved standard of care treatment for this indication
    Other Names:
    • Pemetrexed
    • Cisplatin
  • Other: Placebo plus Pem Cis
    Placebo in combination approved standard of care treatment for this indication
    Other Names:
    • Pemetrexed
    • Cisplatin
Study Arms  ICMJE
  • 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

    Intervention: Drug: ADI-PEG 20 plus Pem Cis
  • 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

    Intervention: Other: Placebo plus Pem Cis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 1, 2016)
386
Original Estimated Enrollment  ICMJE
 (submitted: March 10, 2016)
372
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sonia Doyle 858-452-6688 ext 189 sdoyle@polarispharma.com
Contact: Sandra Dodd 858-452-6688 ext 188 sdodd@polarispharma.com
Listed Location Countries  ICMJE Australia,   Italy,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02709512
Other Study ID Numbers  ICMJE POLARIS2015-003
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Polaris Group
Study Sponsor  ICMJE Polaris Group
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: John S Bomalaski, MD Polaris Group
PRS Account Polaris Group
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP