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

• ClinicalTrials.gov Identifier: NCT02029690
• Recruitment Status: Active, not recruiting
• First Posted: January 8, 2014
• Last Update Posted: March 20, 2019
• Sponsor: Polaris Group
• Information provided by (Responsible Party): Polaris Group

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Pleural Mesothelioma Malignant Advanced; Peritoneal Mesothelioma Malignant Advanced; Non-squamous Non-small Cell Lung Carcinoma; Uveal Melanoma; Hepatocellular Carcinoma; Glioma; Sarcomatoid Carcinoma	Drug: ADI-PEG 20	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 85 participants
• 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)
• Actual Study Start Date: April 23, 2014
• Estimated Primary Completion Date: May 2019
• Estimated Study Completion Date: May 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: ADI-PEG 20; Arginine deiminase formulated with polyethylene glycol	Drug: ADI-PEG 20

Outcome Measures

Primary Outcome Measures :

1. 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 ]
2. Define initial estimates of efficacy, measured by modified RECIST criteria for advanced MPM [ Time Frame: 18 weeks ]

Secondary Outcome Measures :

1. Determine the MTD of ADI-PEG 20 in combination with pemetrexed and cisplatin [ Time Frame: 18 weeks ]

Eligibility Criteria

• 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, 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

Locations

United States, Minnesota

Mayo Clinic Rochester

Rochester, Minnesota, United States, 55902

United Kingdom

Centre for Experimental Cancer Medicine (CECM)

London, England, United Kingdom, EC1M 6BQ

Cambridge Hospital

Cambridge, United Kingdom, CB2 0QQ

Guys Hospital

London, United Kingdom, SE1 7EH

Sponsors and Collaborators

Polaris Group

Investigators

• Principal Investigator: Peter Szlosarek, MD, PhD; Barts Cancer Institute

More Information

• Responsible Party: Polaris Group
• ClinicalTrials.gov Identifier: NCT02029690 History of Changes
• Other Study ID Numbers: POLARIS2013-006
• First Posted: January 8, 2014
• Last Update Posted: March 20, 2019
• Last Verified: March 2019

Keywords provided by Polaris Group:

argininosuccinate synthetase; arginine; arginine deiminase

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Hepatocellular; Mesothelioma; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Adenoma; Neoplasms, Mesothelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Cisplatin; Pemetrexed; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors