E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Malignant pleural mesothelioma |
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E.1.1.1 | Medical condition in easily understood language |
Cancer of the lung lining, usually as a consequence of previous asbestos exposure. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027406 |
E.1.2 | Term | Mesothelioma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10035603 |
E.1.2 | Term | Pleural mesothelioma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059518 |
E.1.2 | Term | Pleural mesothelioma malignant |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
As this is a feasibility study there are no primary or secondary objectives to the trial. The overarching question is whether it would be feasible to run a full trial to determine if the addition of Zoledronic acid to 1st line chemotherapy would confer a further benefit to patients with mesothelioma, with regards to survival. The feasibility of this trial will be assessed along the following criteria: 1. Feasibility of randomising 50 patients in 12 months 2. Acceptability of recruitment procedures, consent and randomisation, and data collection methods. 3. Acceptability of ZA in MPM patients, and the optimal timing and location for ZA administration. 4. Qualitative assessment in a subgroup of 10 patients (from the randomised and non-randomised groups) to evaluate patients' experience in the randomisation and/or recruitment process 5. Quantification of drop-out and data completeness rates 6. Estimates of outcome event rates eg. survival times, measures of mean response and outco |
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E.2.2 | Secondary objectives of the trial |
If this trial proves that it is feasible to run an appropriately statistically powered trial, the outcomes we would be looking for are as below:
• Proportion of patients with progression free survival at 6 months • Time to progression • Overall survival from randomisation • Progression free survival from randomisation • Rate of progression of MPM, as measured by modified RECIST criteria on CT, after 3 cycles of chemotherapy (Pemetrexed/Cisplatin) • Rate of progression in MPM, as measured by modified RECIST criteria on CT, after 6 cycles of chemotherapy. • Tumour metabolic activity as determined by Total glycolytic volume (TGV) on PET-CT scans, after 3 cycles of chemotherapy • Value of TGV or standard uptake value (SUV) in the assessment of disease response/progression • Serum mesothelin as a useful biomarker for monitoring disease and detecting treatment response • Quality of life determined by dyspnoea Visual analogue scale (VAS) scores and EQ5D
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Histo-cytologically confirmed diagnosis of MPM -WHO performance status 0-1 -Eligible for first line chemotherapy treatment -Measurable disease on CT as per modified RECIST criteria (tumour thickness >5mm) -Ability to give informed consent
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E.4 | Principal exclusion criteria |
Not fit for chemotherapy due to performance status or other comorbidities Previous chemotherapy for MPM IV bisphosphonates in the 3 months preceding randomisation Significant renal disease (eGFR < 30ml/min in the last 4 weeks) Hypocalcaemia (current hypocalcaemia on treatment, evidence of hypocalcaemia on most recent blood tests – should be within the last 6 weeks) Known allergy to bisphosphonates or excipients of its preparation Severe untreated dental caries Concomitant participation in another drug trial for mesothelioma Allergy to 18-Fluodeoxyglucose used for the PET scan Women of child bearing potential (defined as fertile, or following menarche and until becoming post-menopausal unless permanently sterile)
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E.5 End points |
E.5.1 | Primary end point(s) |
As this is a feasibility trial,the feasibility assessments will be along the points below:
1. Feasibility of randomising 50 patients over a 12 month period 2. Acceptability of recruitment procedures, consent and randomisation, and data collection methods. 3. Acceptability of ZA in MPM patients, and the optimal timing and location for ZA administration. 4. Qualitative assessment in a subgroup of 10 patients to evaluate patients' experience in the randomisation and recruitment process 5. Quantification of drop-out and data completeness rates 6. Estimates of outcome event rates eg. survival times, measures of mean response and outcome variance (continuous variables such as quality of life) and confidence intervals around estimates of proportions, categorical variables such as recruitment rates)to use for calculating full trial size and number of sites.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Following completion of 6 months of follow-up for all recruited patients |
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E.5.2 | Secondary end point(s) |
-Acceptability of recruitment procedures, consent and randomisation, and data collection methods. -Acceptability of ZA in MPM patients, and the optimal timing and location for ZA administration. -Qualitative assessment in a subgroup of 10 patients to evaluate patients experience in the randomisation and recruitment process -Quantification of drop-out and data completeness rates -Estimates of outcome event rates eg. survival times, measures of mean response and outcome variance (continuous variables such as quality of life) and confidence intervals around estimates of proportions, categorical variables such as recruitment rates)to use for calculation of full trial size and number of recruitment centres |
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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 | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Open label third arm for those not having concurrent chemotherapy |
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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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 0 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 1 |