A Clinical Trial of ADI-PEG 20TM in Patients With Malignant Pleural Mesothelioma

Phase 2

• Conditions: Malignant Pleural Mesothelioma
• Interventions: Drug: ADI-PEG 20

• Registration Number: NCT01279967
• Lead Sponsor: Barts & The London NHS Trust

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-01
• Study First Submitted: 2011-01-19
• Study First Submitted QC: 2011-01-19
• Study First Posted: 2011-01-20
• Status Verified: 2012-05
• Last Update Submitted: 2014-11-19
• Last Update Posted: 2014-11-20
• Primary Completion: 2015-01
• Study Completion: 2015-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 70

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 lab confirmation is required before randomization

3. Performance status ECOG ≤ 1. Life expectancy should be greater than 3 months

4. 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.

5. CT evaluable disease by modified RECIST criteria

6. 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.

7. Adequate hepatic function (AST and ALT < 3 x upper limit of normal; bilirubin < 1.5 x upper limit of normal)

8. Creatinine clearance >30ml/min

9. Able to give written informed consent to participate

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Exclusion Criteria

1. Participation in another clinical trial using an investigational agent
2. Patients with surgically resectable disease
3. Recurrent pleural effusion (not pleurodesed)
4. Receipt of extensive radiation (hemi-thorax) therapy within 6 weeks before enrollment. Radiation to chest port sites following thoracotomy is permitted
5. 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
6. Symptomatic or known brain or leptomeningeal metastases
7. Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment
8. 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
9. Serious medical (e.g. uncontrolled diabetes, hepatic disease, infection, uncontrolled gout) or psychiatric illness likely to interfere with participation in this clinical study
10. History of seizures
11. 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
12. Females must not be breastfeeding
13. Prior exposure to ADI-PEG 20
14. Preplanned surgery or procedures that would interfere with the study protocol
15. Allergy to pegylated products
16. Exposure to another investigational drug within 4 weeks prior to start of study treatment

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
B	ADI-PEG 20	Arm B is the treatment arm with best supportive care plus ADI-PEG20.

Primary Outcome Measures

Name	Time	Method
progression-free survival	18 months

Secondary Outcome Measures

Name	Time	Method
overall survival	18 months
time to progression	18 months
safety (adverse events)	18 months
response rate	18 months

Trial Locations

Locations (7)

The Royal Sussex County Hospital; 🇬🇧 Brighton, United Kingdom

Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital; 🇬🇧 Cambridge, United Kingdom

Hull and East Yorkshire Hospitals NHS Trust,The Princess Royal Hospital; 🇬🇧 Hull, United Kingdom

Guy's and St Thomas' Foundation Trust, Guy's Hospital; 🇬🇧 London, United Kingdom

University Hospital of South Manchester NHS Foundation Trust, Wythenshawe Hospital; 🇬🇧 Manchester, United Kingdom

Southampton University Hospitals NHS Trust, Southampton General Hospital; 🇬🇧 Southampton, United Kingdom

Barts and The London NHS, St Bartholomew's Hospital; 🇬🇧 London, United Kingdom