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Ph 1 Study in Subjects With Tumors Requiring Arginine to Assess ADI-PEG 20 With Pemetrexed and Cisplatin (TRAP)

This study is currently recruiting participants.
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Verified August 2016 by Polaris Group
Information provided by (Responsible Party):
Polaris Group Identifier:
First received: December 16, 2013
Last updated: April 3, 2017
Last verified: August 2016
A study of ADI-PEG 20 (pegylated arginine deiminase), an arginine degrading enzyme in patients with histologically proven advanced malignant pleural mesothelioma (MPM), advanced peritoneal mesothelioma (in dose escalation cohort only), non-squamous non-small cell lung carcinoma stage IIIB/IV (NSCLC), metastatic uveal melanoma, hepatocellular carcinoma (HCC), glioma and sarcomatoid cancers

Condition Intervention Phase
Pleural Mesothelioma Malignant Advanced Peritoneal Mesothelioma Malignant Advanced Non-squamous Non-small Cell Lung Carcinoma Stage IIIB/IV (NSCLC) Metastatic Uveal Melanoma Hepatocellular Carcinoma (HCC) Glioma Sarcomatoid Cancers Drug: ADI-PEG 20 Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Study in Subjects With Tumors Requiring Arginine to Assess ADI-PEG 20 With Pemetrexed and Cisplatin (ADIPemCis) (TRAP Study)

Resource links provided by NLM:

Further study details as provided by Polaris Group:

Primary Outcome Measures:
  • Define initial estimates of efficacy, measured by RECIST 1.1 criteria for non-squamous NSCLC, advanced peritoneal mesothelioma, metastatic uveal melanoma, HCC, glioma and sarcomatoid cancers for ADI-PEG 20 in combination with pemetrexed and cisplatin. [ Time Frame: 18 weeks ]
  • Define initial estimates of efficacy, measured by modified RECIST criteria for advanced MPM [ Time Frame: 18 weeks ]

Secondary Outcome Measures:
  • Determine the MTD of ADI-PEG 20 in combination with pemetrexed and cisplatin [ Time Frame: 18 weeks ]

Estimated Enrollment: 88
Study Start Date: April 2014
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ADI-PEG 20
Arginine deiminase formulated with polyethylene glycol
Drug: ADI-PEG 20

Detailed Description:
Weekly ADI-PEG 20 will be cohort dose escalated (18, 27 and 36 mg/m2), with pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 both given every 3 weeks. Subjects may receive a maximum of 6, 3-week cycles of ADIPemCis for a total of 18 weeks of treatment. Subjects with NSCLC may receive 4 to 6, 3-week cycles as per local institutional policy. Those subjects completing ADIPemCis treatment may continue on ADI-PEG 20 monotherapy if they have SD or better. Subjects with NSCLC may continue to receive pemetrexed as per local institutional policy along with ADI-PEG 20 and/or continue on ADI-PEG 20 monotherapy after pemetrexed is also discontinued.

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

Inclusion Criteria:

  1. Histologically proven advanced MPM, advanced peritoneal mesothelioma (for dose escalation cohort only) or non-squamous NSCLC (stage IIIB/IV) who have not been treated with prior chemotherapy or immunotherapy, except that NSCLC subjects with EGFR mutant or ALK positive must have had an EGFR tyrosine kinase inhibitor (TKI) or ALK inhibitor and progressed or been shown to be intolerant of therapy prior to enrolling in this trial, if such ALK inhibitor and EGFR targeted therapy are approved and available in the country in which patients are being enrolled OR Histologically proven metastatic uveal melanoma who have not been treated with prior chemotherapy (MTD cohort only), OR Histologically proven HCC who have failed (PD and/or side effects-been intolerant of) treatment with sorafenib. Failure is defined as having progressed radiographically on, or been intolerant to prior systemic therapy. Intolerance is defined as discontinuation due to an AE(s) on prior systemic therapy that was unacceptable to the treating physician and / or patient, with or without dose interruption and modification. Failure requires at least 14 days of treatment with sorafenib, except for a subject that has had a severe allergic reaction to sorafenib at any time, even less than 14 days of treatment with sorafenib and thus it would be imprudent to re-challenge them with that agent. Cirrhotic status of Child-Pugh grade A-B7 must be present. Child-Pugh status should be determined based on clinical findings and laboratory data during the screening period (Appendix E). Subjects on anti-coagulants are to receive 1 point for their INR status, as they are presumed to have a <1.7 baseline PT/INR.", OR Histologically proven high-grade glioma who have failed (PD and/or side effects) treatment with radiotherapy ± temozolomide, OR Sarcomatoid cancer of any line.
  2. ASS1 deficiency (defined as ≤50% ASS expression) demonstrated on tissue specimen (cytospin samples are acceptable) by immunohistochemistry (IHC). For subjects previously treated with chemotherapy, this specimen may have been obtained before that chemotherapy. A new tissue specimen obtained after most recent chemotherapy is not required. Thus ASS1 deficiency is required for entrance into the study. If tissue is not available to determine ASS1 deficiency, then tissue must be obtained by biopsy to determine ASS1 status.
  3. Measurable disease as assessed by modified RECIST for MPM and by RECIST 1.1 criteria for peritoneal mesothelioma, NSCLC, uveal melanoma, HCC, glioma and sarcomatoid carcinoma
  4. ECOG performance status of 0 - 1
  5. Predicted life expectancy of at least 12 weeks.

Exclusion Criteria:

  1. Radiotherapy (except for palliative reasons), targeted therapy, or immunotherapy (except for uveal melanoma) the previous four weeks before study treatment.
  2. Ongoing toxic manifestations of previous treatments.
  3. Symptomatic brain or spinal cord metastases (patients must be stable for > 3 months post radiotherapy or surgery) for subjects with mesothelioma, NSCLC, uveal melanoma excludes subjects with HCC or glioma).
  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 to the first dose of study treatment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02029690

Contact: John Bomalaski, MD 858-452-6688 ext 114
Contact: Sonia Doyle 858-452-6688 ext 189

United Kingdom
Centre for Experimental Cancer Medicine (CECM) Recruiting
London, England, United Kingdom, EC1M 6BQ
Contact: Peter Szlosarek, MD, PhD   
Sponsors and Collaborators
Polaris Group
Principal Investigator: Peter Szlosarek, MD, PhD Barts Cancer Institute
  More Information

Responsible Party: Polaris Group Identifier: NCT02029690     History of Changes
Other Study ID Numbers: POLARIS2013-006
Study First Received: December 16, 2013
Last Updated: April 3, 2017

Keywords provided by Polaris Group:
argininosuccinate synthetase
arginine deiminase

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Neoplasms, Mesothelial
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors processed this record on September 21, 2017