Malignant Pleural Mesothelioma
Conditions
Keywords
Pleural Mesothelioma, ADI-PEG 20
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.
Interventions
DRUGADI-PEG 20
36.8mg/m2 based on BSA, weekly treatment for 6 months
Sponsors
Cancer Research UK
UK: Barts Center for Experimental Cancer Medicine (CECM) for Trial Coordination
Barts & The London NHS Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| progression-free survival | 18 months |
Secondary
| Measure | Time frame |
|---|---|
| response rate | 18 months |
| overall survival | 18 months |
| time to progression | 18 months |
| safety (adverse events) | 18 months |
Countries
United Kingdom
Outcome results
None listed