NCT01279967

Brief Summary

To examine whether the arginine depleting drug, ADI-PEG 20, might be effective as a targeted therapy in patients with ASS-negative malignant pleural mesothelioma.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
70

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jan 2011

Typical duration for phase_2

Geographic Reach
1 country

7 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2011

Completed
18 days until next milestone

First Submitted

Initial submission to the registry

January 19, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 20, 2011

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2015

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2015

Completed
Last Updated

November 20, 2014

Status Verified

May 1, 2012

Enrollment Period

4 years

First QC Date

January 19, 2011

Last Update Submit

November 19, 2014

Conditions

Malignant Pleural Mesothelioma

Keywords

Pleural MesotheliomaADI-PEG 20

Outcome Measures

Primary Outcomes (1)

  • progression-free survival

    18 months

Secondary Outcomes (4)

  • response rate

    18 months

  • overall survival

    18 months

  • time to progression

    18 months

  • safety (adverse events)

    18 months

Study Arms (2)

A

NO INTERVENTION

Arm A is control arm with best supportive care.

B

EXPERIMENTAL

Arm B is the treatment arm with best supportive care plus ADI-PEG20.

Drug: ADI-PEG 20

Interventions

ADI-PEG 20DRUG

36.8mg/m2 based on BSA, weekly treatment for 6 months

B

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Males and Females aged 18 years and older. (There is no upper age limit)
  • Histopathological evidence of ASS-negative MPM. All biopsies will be reviewed for ASS expression using immunohistochemistry. Central lab confirmation is required before randomization
  • Performance status ECOG ≤ 1. Life expectancy should be greater than 3 months
  • Chemo-naive patients OR, Patients who have been previously treated with platinum-based combination chemotherapy with progressive disease at entry. In the event of a baseline diagnostic ASS-positive test, a repeat biopsy confirming loss of ASS expression will be required post platinum-based combination chemotherapy, with at least a 4 week interval from the last treatment episode.
  • CT evaluable disease by modified RECIST criteria
  • Adequate bone marrow function, or supported through treatment:
  • Haemoglobin 10g/dl or greater.
  • White cell count 2 x 109/L or greater, neutrophil count 1.5 x 109/L or greater
  • Platelets 75 x 109 /L or greater.
  • Adequate hepatic function (AST and ALT \< 3 x upper limit of normal; bilirubin \< 1.5 x upper limit of normal)
  • Creatinine clearance \>30ml/min
  • Able to give written informed consent to participate

You may not qualify if:

  • Participation in another clinical trial using an investigational agent
  • Patients with surgically resectable disease
  • Recurrent pleural effusion (not pleurodesed)
  • Receipt of extensive radiation (hemi-thorax) therapy within 6 weeks before enrollment. Radiation to chest port sites following thoracotomy is permitted
  • A history of prior malignant tumour, unless the patient has been without evidence of disease for at least three years, or the tumour was a non-melanoma skin tumour or in-situ cervix carcinoma
  • Symptomatic or known brain or leptomeningeal metastases
  • Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment
  • New York Heart Association (NYHA) Class III or IV heart failure (Attachment 10, NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
  • Serious medical (e.g. uncontrolled diabetes, hepatic disease, infection, uncontrolled gout) or psychiatric illness likely to interfere with participation in this clinical study
  • History of seizures
  • Patients of child-bearing age must not become pregnant. Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy. All patients enrolled on the study must agree to use acceptable birth control measures whilst on the study; using both barrier and hormonal methods. Patients that are surgically sterile are also eligible to participate in this study
  • Females must not be breastfeeding
  • Prior exposure to ADI-PEG 20
  • Preplanned surgery or procedures that would interfere with the study protocol
  • Allergy to pegylated products
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

The Royal Sussex County Hospital

Brighton, BN2 5BE, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Hull and East Yorkshire Hospitals NHS Trust,The Princess Royal Hospital

Hull, HU8 9HE, United Kingdom

Location

Barts and The London NHS, St Bartholomew's Hospital

London, EC1 A 7BE, United Kingdom

Location

Guy's and St Thomas' Foundation Trust, Guy's Hospital

London, SE1 9RT, United Kingdom

Location

University Hospital of South Manchester NHS Foundation Trust, Wythenshawe Hospital

Manchester, M23 9LT, United Kingdom

Location

Southampton University Hospitals NHS Trust, Southampton General Hospital

Southampton, SO16 6 YD, United Kingdom

Location

Related Publications (2)

  • Szlosarek PW, Luong P, Phillips MM, Baccarini M, Stephen E, Szyszko T, Sheaff MT, Avril N. Metabolic response to pegylated arginine deiminase in mesothelioma with promoter methylation of argininosuccinate synthetase. J Clin Oncol. 2013 Mar 1;31(7):e111-3. doi: 10.1200/JCO.2012.42.1784. Epub 2013 Jan 14. No abstract available.

    PMID: 23319692BACKGROUND

  • Szlosarek PW, Steele JP, Nolan L, Gilligan D, Taylor P, Spicer J, Lind M, Mitra S, Shamash J, Phillips MM, Luong P, Payne S, Hillman P, Ellis S, Szyszko T, Dancey G, Butcher L, Beck S, Avril NE, Thomson J, Johnston A, Tomsa M, Lawrence C, Schmid P, Crook T, Wu BW, Bomalaski JS, Lemoine N, Sheaff MT, Rudd RM, Fennell D, Hackshaw A. Arginine Deprivation With Pegylated Arginine Deiminase in Patients With Argininosuccinate Synthetase 1-Deficient Malignant Pleural Mesothelioma: A Randomized Clinical Trial. JAMA Oncol. 2017 Jan 1;3(1):58-66. doi: 10.1001/jamaoncol.2016.3049.

    PMID: 27584578DERIVED

Related Links

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

ADI PEG20

Condition Hierarchy (Ancestors)

MesotheliomaAdenomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsNeoplasms, MesothelialLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SitePleural NeoplasmsLung DiseasesRespiratory Tract Diseases

Study Officials

  • Peter Szlosarek

    Barts and the London NHS

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 19, 2011

First Posted

January 20, 2011

Study Start

January 1, 2011

Primary Completion

January 1, 2015

Study Completion

March 1, 2015

Last Updated

November 20, 2014

Record last verified: 2012-05

Locations

GB(7)