Clinical Trials /

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

NCT02709512

Description:

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.

Related Conditions:
  • Pleural Biphasic Mesothelioma
  • Pleural Mesothelioma, Sarcomatoid Type
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: POLARIS2015-003
  • NCT ID: NCT02709512

Conditions

  • Mesothelioma

Interventions

DrugSynonymsArms
ADI-PEG 20 plus Pem CisPemetrexed, CisplatinDrug: ADI-PEG 20 plus Pem Cis

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Drug: ADI-PEG 20 plus Pem CisExperimentalDose: 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
  • ADI-PEG 20 plus Pem Cis
Drug: Placebo plus Pem CisPlacebo ComparatorDose: 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

    Eligibility 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.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Response Rate
    Time Frame:approximately 18 months
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Progression Free Survival
    Time Frame:approximately 18 months
    Safety Issue:
    Description:

    Details

    Phase:Phase 2/Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Polaris Group

    Trial Keywords

    • Malignant Pleural Mesothelioma with Low Argininosuccinate Synthetase 1 Expression

    Last Updated

    January 25, 2017