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Pleural Mesothelioma Malignant AdvancedPhase 1TRAPNCT02029690

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

A Phase 1 study testing ADI-PEG 20 in people with Pleural Mesothelioma Malignant Advanced and Peritoneal Mesothelioma Malignant Advanced, run by Polaris Group at 4 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ADI-PEG 20
Could I receive a placebo?
No, everyone receives an active treatment
How many people
85 participants
Where
4 sitesin 2 countries
Study dates
23 Apr 2014to Jun 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

United Kingdom3 sites

  • Cambridge Hospital

    Cambridge, CB2 0QQ

  • Centre for Experimental Cancer Medicine (CECM)

    London, England, EC1M 6BQ

  • Guys Hospital

    London, SE1 7EH

Other trials in United Kingdom

United States1 site

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55902

Other trials in United States

About this study

Official title: Phase 1 Study in Subjects With Tumors Requiring Arginine to Assess ADI-PEG 20 With Pemetrexed and Cisplatin (ADIPemCis) (TRAP Study)

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

Read the 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.

Being tested
ADI-PEG 20
Keywords
argininosuccinate synthetase, arginine, arginine deiminase
Medical subject headings
Uveal Melanoma, Carcinoma, Hepatocellular, Glioma, Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ADI-PEG 20Drug

Study groups in NCT02029690
Study groupRoleWhat they receive
ADI-PEG 20ExperimentalArginine deiminase formulated with polyethylene glycol
Receives: Drug: ADI-PEG 20

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 18 weeks

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

    Measured: 18 weeks

Secondary outcomes (1)

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

    Measured: 18 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jan 2014 (estimated)
  2. Study start23 Apr 2014
  3. Primary completion15 Aug 2018
  4. Study completionJun 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
85 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02029690
Sponsor's protocol ID
POLARIS2013-006
Acronym
TRAP
Status last verified
Mar 2019
First submitted
16 Dec 2013
Last updated
25 Sep 2020
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 35466524

  • 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.

    PubMed 34382365

  • 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.

    PubMed 30796035

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ADI-PEG 20 in people with Pleural Mesothelioma Malignant Advanced and Peritoneal Mesothelioma Malignant Advanced, run by Polaris Group at 4 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United Kingdom, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early. Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02029690, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2020.

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