Condition category
Cancer
Date applied
12/10/2009
Date assigned
12/10/2010
Last edited
20/07/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Peter Szlosarek

ORCID ID

Contact details

Centre for Molecular Oncology and Imaging
Institute of Cancer and CR-UK Clinical Centre
Queen Mary University of London
Barts and The London School of Medicine
John Vane Science Centre
Charterhouse Square
London
EC1M 6BQ
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT01279967

Protocol/serial number

# 006836

Study information

Scientific title

A randomised stratified multicentre phase II clinical trial of single agent pegylated arginine deiminase (ADI-PEG 20) in patients with malignant pleural mesothelioma

Acronym

ADAM

Study hypothesis

Mesothelioma is a profoundly apoptosis resistant malignancy with the benefit of palliative chemotherapy confined to a subgroup of patients (less than 40%). The rationale underlying arginine depletion with ADI-PEG 20 is that arginine auxotrophic tumours undergo programmed cell death or apoptosis, due to an absence of the rate-limiting enzyme for arginine biosynthesis, ASS1. We have documented that ASS1 is commonly absent in patients with malignant pleural mesothelioma (MPM) and that ADI-PEG 20 induces apoptosis of ASS1 negative MPM tumours. This study seeks to define the role of ADI-PEG 20 in patients with confirmed ASS1-negative MPM, whilst avoiding the known difficulties inherent in MPM response assessments, with a best supportive care control arm. Patients who are either not keen or unfit for front-line chemotherapy, will be randomised into this window study.

The main purpose of this study is to look at the effectiveness of ADI-PEG 20 at controlling mesothelioma in patients who do not receive chemotherapy. We will also compare the results with patients who receive best supportive care only.

Ethics approval

The South East research Ethics committee, South East Coast Strategic Health Authority on 30/12/2009 (ref: 09/H1102/107). Amendments approved on 06/07/2010 and 04/10/2010.

Study design

Randomised stratified multicentre phase II clinical trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please contact ADAM study Coordinator, Li-Hui Chen (adam@qmcr.qmul.ac.uk) to request a patient information sheet

Condition

Malignant pleural mesothelioma

Intervention

Patients with ASS1-negative mesothelioma confirmed by immunohistochemistry will be randomised as follows:
Arm A: Best supportive care (n = 21)
Arm B: ADI-PEG 20 and best supportive care (n = 42)

Assessment of tumoural ASS1 status by immunohistochemistry and a baseline PET-CT will take place. Patients randomised to Arm B will receive a weekly intramuscular injection of ADI-PEG 20 and weekly routine blood tests, PD and PK bloods. A repeat PET-CT will be performed between week 3 and 4 on the protocol for patients in Arm B. All patients (Arm A and B) will be followed up on a regular basis with a CT scan every 2 months. Monthly bloods and urine collection for translational research. A repeat tumoural biopsy on progression in a patient with an initial response to ADI-PEG 20.

Intervention type

Drug

Phase

Phase II

Drug names

Pegylated arginine deiminase (ADI-PEG 20)

Primary outcome measures

Progression-free survival, measured from the date of randomisation until the date of progression or death, whichever occurs first.

Secondary outcome measures

1. Response rate, measured by image assessment every two months
2. Median overall survival
3. Toxicity, measured continuously throughout the study

Overall trial start date

01/01/2010

Overall trial end date

21/05/2013

Reason abandoned

Eligibility

Participant inclusion criteria

1. Males and females aged 18 years and older (there is no upper age limit)
2. Histopathological evidence of ASS-negative MPM. All biopsies will be reviewed for ASS expression using immunohistochemistry (central review by Dr Michael Sheaff, Institute of Cell and Molecular Sciences, Barts and The London School of Medicine)
3. Performance status Eastern Cooperative Oncology Group (ECOG) 0 - 1
4. No prior systemic chemotherapy
5. Computed tomography (CT) evaluable disease by modified Response Evaluation Criteria in Solid Tumours (RECIST) criteria
6. Adequate haematological status (haemoglobin 10 g/dl or greater; white cell count 2 x 10^9/L or greater, neutrophil count 1.5 x 10^9/L or greater; platelets 100 x 10^9 /L or greater)
7. Adequate hepatic function (bilirubin less than 1.5 x upper limit of normal; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 3 x upper limit of normal)
8. Creatinine clearance greater than 30 ml/min
9. Willing to give written informed consent to participate

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

63

Participant exclusion criteria

1. Any of the above inclusion criteria are not met
2. Enrolment in another clinical trial
3. Patients with surgically resectable disease
4. Recurrent pleural effusion (not pleurodesed)
5. Receipt of extensive radiation (hemi-thorax) therapy within 6 weeks before enrolment. Radiation to chest port sites following thoracotomy is permitted.
6. 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
7. Symptomatic or known brain or leptomeningeal metastases
8. Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment
9. 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
10. Serious medical (e.g. uncontrolled diabetes, hepatic disease, infection) or psychiatric illness likely to interfere with participation in this clinical study
11. History of seizures
12. 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. Acceptable birth control measures whilst on the study include barrier and hormonal methods; patients that are surgically sterile are also eligible to participate in this study.
13. Females must not be breastfeeding
14. Prior exposure to ADI-PEG 20
15. Pre-planned surgery or procedures that would interfere with the study protocol
16. Allergy to pegylated products

Recruitment start date

02/03/2011

Recruitment end date

21/05/2013

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Queen Mary University of London
London
EC1M 6BQ
United Kingdom

Sponsor information

Organisation

Barts and The London NHS Trust (UK)

Sponsor details

Mr Gerry Leonard
Head of Research Resources
Joint Research and Development Office
Queen Mary Innovation Centre
5 Walden Street
London
E1 2EF
United Kingdom

Sponsor type

Government

Website

http://www.bartsandthelondon.nhs.uk/research/

Funders

Funder type

Charity

Funder name

Cancer Research UK (CRUK) (UK) - (ref:C12522/A7740)

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes