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

NCT02029690 | Terminated Phase 1

• 1 other identifier: POLARIS2013-006
• Study Type: interventional
• Target: 85
• Locations: 2 countries
• Sites: 4

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

Conditions

Pleural Mesothelioma Malignant Advanced; Peritoneal Mesothelioma Malignant Advanced; Non-squamous Non-small Cell Lung Carcinoma; Uveal Melanoma; Hepatocellular Carcinoma; Glioma; Sarcomatoid Carcinoma

Keywords

argininosuccinate synthetase; arginine; arginine deiminase

Outcome Measures

Primary Outcomes (2)

• 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.

  18 weeks

• Define initial estimates of efficacy, measured by modified RECIST criteria for advanced MPM

  18 weeks

Secondary Outcomes (1)

• Determine the MTD of ADI-PEG 20 in combination with pemetrexed and cisplatin

  18 weeks

Study Arms (1)

ADI-PEG 20

EXPERIMENTAL

Arginine deiminase formulated with polyethylene glycol

Drug: ADI-PEG 20

Interventions

ADI-PEG 20 DRUG

ADI-PEG 20

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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
• ECOG performance status of 0 - 1
• Predicted life expectancy of at least 12 weeks.

You may not qualify if:

• Radiotherapy (except for palliative reasons), targeted therapy, or immunotherapy (except for uveal melanoma) the previous four weeks before study treatment.
• Ongoing toxic manifestations of previous treatments.
• 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).
• Major thoracic or abdominal surgery from which the patient has not yet recovered.
• 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.

Sponsors & Collaborators

• Polaris Group: lead

Study Sites (4)

Mayo Clinic Rochester

Rochester, Minnesota, 55902, United States

Location

Centre for Experimental Cancer Medicine (CECM)

London, England, EC1M 6BQ, United Kingdom

Location

Cambridge Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Guys Hospital

London, SE1 7EH, United Kingdom

Location

Related Publications (3)

• Chan PY, Phillips MM, Ellis S, Johnston A, Feng X, Arora A, Hay G, Cohen VML, Sagoo MS, Bomalaski JS, Sheaff MT, Szlosarek PW. A Phase 1 study of ADI-PEG20 (pegargiminase) combined with cisplatin and pemetrexed in ASS1-negative metastatic uveal melanoma. Pigment Cell Melanoma Res. 2022 Jul;35(4):461-470. doi: 10.1111/pcmr.13042. Epub 2022 May 16.

  PMID: 35466524 DERIVED

• Szlosarek PW, Wimalasingham AG, Phillips MM, Hall PE, Chan PY, Conibear J, Lim L, Rashid S, Steele J, Wells P, Shiu CF, Kuo CL, Feng X, Johnston A, Bomalaski J, Ellis S, Grantham M, Sheaff M. Phase 1, pharmacogenomic, dose-expansion study of pegargiminase plus pemetrexed and cisplatin in patients with ASS1-deficient non-squamous non-small cell lung cancer. Cancer Med. 2021 Oct;10(19):6642-6652. doi: 10.1002/cam4.4196. Epub 2021 Aug 12.

  PMID: 34382365 DERIVED

• Hall PE, Lewis R, Syed N, Shaffer R, Evanson J, Ellis S, Williams M, Feng X, Johnston A, Thomson JA, Harris FP, Jena R, Matys T, Jefferies S, Smith K, Wu BW, Bomalaski JS, Crook T, O'Neill K, Paraskevopoulos D, Khadeir RS, Sheaff M, Pacey S, Plowman PN, Szlosarek PW. A Phase I Study of Pegylated Arginine Deiminase (Pegargiminase), Cisplatin, and Pemetrexed in Argininosuccinate Synthetase 1-Deficient Recurrent High-grade Glioma. Clin Cancer Res. 2019 May 1;25(9):2708-2716. doi: 10.1158/1078-0432.CCR-18-3729. Epub 2019 Feb 22.

  PMID: 30796035 DERIVED

MeSH Terms

Conditions

Uveal Melanoma; Carcinoma, Hepatocellular; Glioma; Carcinoma

Interventions

ADI PEG20

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Neuroepithelial

Study Officials

• Peter Szlosarek, MD, PhD

  Barts Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2013
• First Posted: January 8, 2014
• Study Start: April 23, 2014
• Primary Completion: August 15, 2018
• Study Completion: June 1, 2020
• Last Updated: September 25, 2020

Record last verified: 2019-03

Locations

US (1); GB (3)