Mesothelioma
Conditions
Interventions
Product Name: Pegylated Arginine Deiminase
Pharmaceutical Form:
Sponsors
Barts Health NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion 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.No prior systemic chemotherapy for mesothelioma 5.CT evaluable disease by modified RECIST criteria 6.Adequate bone marrow function, or supported through treatment: a.Haemoglobin 10g/dl or greater. b.White cell count 2 x 109/L or greater, neutrophil count 1.5 x 109/L or greater c.Platelets 75 x 109 /L or greater. 7.Adequate hepatic function (AST and ALT 30ml/min 9.Able to give written informed consent to participate. NB: Translational research (tissue donation) will be dealt with by a separate informed consent form. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Exclusion Criteria 1.Particiaption 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) 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the time to disease progression between the control group receiving best supportive care and the group receiving ADI-PEG 20 and best supportive care.;Secondary Objective: The following will be assessed in control and ADI-PEG-20 groups: i)To measure the response rate (partial response (PR) and complete response (CR) ii)To measure the median overall survival rates (or at 18 month survival) iii)To assess the safety (adverse events) Tertiary and Exploratory Objectives Tertiary i)To measure peripheral blood arginine and citrulline levels, levels of ADI-PEG 20 and development of antibodies to ADI-PEG 20 ii)To measure serum mesothelin as a tumour marker for the management of patients with MPM Exploratory Objectives i)Pharmacogenomics Construction of a cDNA library to enable microarray analysis to establish clinically relevant biomarkers. Tumour and peripheral blood leukocyte genomic DNA will be obtained and banked to enable prospective pharmacogenomic studies. These may include analysis of gene copy number by microarray-based comparative genomic hybridization (CGH) analysis and single nucleotide polymorphism (SNP) microarray analyses;Primary end point(s): The rate of progression or death at 6 months after enrollment. Time to disease progression will be defined according to the modified RECIST criteria and will be measured from patient entry onto the protocol to when the disease starts to worsen | — |
Countries
United Kingdom
Outcome results
None listed