E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 < 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. NB: Translational research (tissue donation) will be dealt with by a separate informed consent form.
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E.4 | Principal 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
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E.5 End points |
E.5.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |