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

• To examine progression-free survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

• To measure the response rate [ Time Frame: 18 months ] [ Designated as safety issue: No ]
• To measure overall survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
• To measure time to progression [ Time Frame: 18 months ] [ Designated as safety issue: No ]
• To assess safety (adverse events) [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

Eligibility Criteria

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 (see Appendix D).
4. Chemo-naive patients OR Patients who have been previously treated with platinum-based combination chemotherapy with progressive disease at entry.
5. CT evaluable disease by modified RECIST criteria.
6. Adequate bone marrow function, or supported through treatment:
   1. Haemoglobin 10g/dl or greater.
   2. White cell count 2 x 109/L or greater, neutrophil count 1.5 x 109/L or greater.
   3. 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.

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