E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Histologically confirmed malignant pleural mesothelioma |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 17.1 |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective of this trial is to determine whether treatment with vinorelbine in patients with malignant mesothelioma improves overall survival. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this trial are to determine if vinorelbine is a safe, feasible and tolerable as a second line therapy in patients with malignant mesothelioma. Other anti-tumour activities as measured by response, tumour volume reduction and progression free survival will be also be determined. Finally, the study will also be used to collect blood and tissue samples from this population to facilitate future translational research including investigation of BRCA1 expression as a putative predictor of vinorelbine sensitivity. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The translational sub-study is part of the main VIM trial protocol. Of the 200 enrolled into VIM, tissue samples will be collected on all patients at baseline, with an optional re-biopsy at disease progression for patients randomised to the treatment arm. Research blood samples will be collected from all patients pre-randomisation and at disease progression for patients randmomised to the treatment arm. |
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E.3 | Principal inclusion criteria |
1.Confirmed histological diagnosis of malignant pleural mesothelioma. The same block or 10 unstained slides should be available for translational research 2.Prior treatment with first-line standard platinum doublet based chemotherapy only 3.Evidence of disease progression according to CT scan 4.Life expectancy ≥ 3 months 5.ECOG performance status 0-2 6.Men or women aged 18 years or over 7.Willing to consent to provide blood and tissue for translational research 8.Disease which is measurable using modified RECIST. 9.Adequate organ function, including the following: Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, WBC >3 x 109/L, haemoglobin ≥ 100g/L, platelets ≥ 100 x 109/L; adequate liver function: Bilirubin <1.5 x ULN AST/ALT 1.5- 2.5 x ULN. 10.Patients with reproductive potential (male or female), who are sexually active during the duration of the trial or the drug washout period, should be prepared to use two effective forms of contraception throughout their participation in the trial and for at least three months after the last dose of vinorelbine. 11.Patients must provide informed consent before any study specific procedures.
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E.4 | Principal exclusion criteria |
1.Patients with a diagnosis of a second malignancy except prostate or cervical cancer in remission or patients with a diagnosis of basal cell carcinoma of the skin. 2.Have received treatment with an agent that has no marketing authorisation, within 30 days of study entry. 3.Are pregnant or breastfeeding. If a participant becomes pregnant during the trial, and is randomised to the treatment arm, vinorelbine must be discontinued and the participant followed up until birth or termination of pregnancy. Breastfeeding must be avoided as it is unknown whether vinorelbine is excreted in human milk. 4.Uncontrolled CNS disease. 5.Known contraindication or hypersensitivity to vinorelbine or other vinca alkaloids or to any of the constituents 6.Any disease significantly affecting absorption 7.Previous significant surgical resection of stomach or small bowel 8.Yellow fever vaccine within 30 days of consent 9.Previous vinca alkaloid chemotherapy 10.Palliative radiotherapy within the RECIST area in the 4 weeks prior to baseline CT chest up until randomisation. 11.Patients that are unable to swallow
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival, which is the time from randomisation to death. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1)Progression free survival (PFS) using modified RECIST 2)Safety, tolerability (side effects) and feasibility of use (number of participants requiring does delays or reductions and/or treatment withdrawal) 3)Objective response rate as assessed by modified RECIST |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
PFS and objective response rate will be assessed at the end of the 2 years that the trial is open to recruitment
Safety; SAEs are collected in real time. After 10 patients have completed trial treatment, SAEs and toxicities will be presented to the IDMC for a recommendation as to whether or not to continue recruitment. Toxicities will be collected 90 days after treatment.
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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 | 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) | 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 | No |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
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 | No |
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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The end date is the date of last data capture. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 1 |