E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Malignant Pleural Mesothelioma (in first line, and second line treatment settings) |
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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 objective tumour response, measured as Complete Response (CR ) and Partial Response (PR) rates as determined using the modified RECIST criteria based on the baseline sum of the longest diameters of pleural thickening at three different levels. |
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E.2.2 | Secondary objectives of the trial |
i) To measure progression free survival, and median overall survival rates (2 year survival, as follow up is capped at 2 years); ii) To assess safety and toxicity in this population; iii) To assess quality of life using the lung cancer symptom score (LCSS-meso).
iv) Exploratory translational research (substudy):
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1) Histopathological evidence of MPM 2) Performance status ECOG 0-2. 3) Adequate haematological status: 3a) Haemoglobin 10g/dl or greater. 3b) White cell count 1 x 10(9)/L or greater, neutrophil count 1.5 x 10(9)/L or greater. 4) Platelets 100 x 10(9) /L or greater. 5) Adequate hepatic function (AST and ALT < 3 x upper limit of normal). 6) Willing to give written informed consent to participate. Translational research will be dealt with by a separate informed consent form. 7) Where possible, pleural effusions should be drained before treatment. For uncontrollable pleural effusions (recurrent despite regular drainage), talc or tetracycline pleurodesis may be offered as per standard practice. 8) Male subject agrees to use an acceptable method of birth control for the duration of the study and contraception must be used by women of child bearing potential.
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E.4 | Principal exclusion criteria |
1) Any of the inclusion criteria are not met 2) Enrollment in another clinical trial. 3) The patient has 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. 4) Symptomatic or known Brain or leptomeningeal metastases. 5) Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, 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. 6) Patients may not have received more than 1 prior line of anti-neoplastic treatment for MPM. 7) Prior exposure to VELCADE. 8) Pregnant or breastfeeding. 9) Neuropathy Grade 2. 10) Preplanned surgery or procedures that would interfere with the conduct of the study. 11) Receipt of extensive radiation therapy, systemic chemotherapy, or other anti-neoplastic therapy within 4 weeks before enrollment. 12) Serious medical (e.g. uncontrolled diabetes, hepatic disease, infection,) or psychiatric illness likely to interfere with participation in this clinical study. 13) Have received an experimental drug or used an experimental medical device within 4 weeks before the planned start of treatment. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study. Concurrent participation in any treatment studies is not allowed.
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E.5 End points |
E.5.1 | Primary end point(s) |
Response rate. Continued accrual during the trial will be based upon the objective response rates in the first stage of the two-stage design for patients treated in the first or second line settings. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
including translational research substudy |
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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 | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Simon's 2-Stage Optimal Design, in first and second-line setting |
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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 | No |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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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End of trial: completion of all assessments at Week 20 of the study. Patients who have at least stable disease at week 20, may continue the treatment with single agent VELCADE using the same treatment visit schedule until progressive disease. The decision to continue or not is left at the discretion of the investigator. All subjects will be followed up for 2 year survival. A subject may voluntarily withdraw, or the Investigator may withdraw subjects from the trial at any time per ICH/GCP. |
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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 | 5 |
E.8.9.1 | In the Member State concerned days | |
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 | 5 |