E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Mesothelioma is a type of cancer that can develop in the tissues covering the lungs or the abdomen |
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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 | 20.0 |
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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This trial aims to determine whether nivolumab increases overall survival in patients with relapsed mesothelioma. |
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E.2.2 | Secondary objectives of the trial |
To determine whether nivolumab: a) increases the length of time patients are free from disease (progression-free survival) b) increases response rate to treatment c) is safe and patients are able to tolerate the treatment d) to ascertain how a patients PD-L1 status links with overall survival. e) results in acceptable patient quality of life and cost per quality adjusted life year (QALY)
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1) Histological confirmation of mesothelioma 2) Prior treatment with at least one line of platinum based chemotherapy 3) ECOG Performance Status 0-1 4) Evidence of disease progression (which is radiologically assessable through RECIST) on CT scan 5) Age 18 and above 6) Screening laboratory values within protocol specified ranges 7) Willing to use adequate contraception methods where applicable 8) Willing to provide blood and tissue samples relating to mesothelioma 9) Expected survival of at least 12 weeks
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E.4 | Principal exclusion criteria |
Patients meeting the following criteria will be excluded: 1) Untreated, symptomatic CNS metastases 2) Carcinomatous meningitis 3) Active, known or suspected auto-immune disease 4) Those requiring systemic treatment with corticosteroids or immunosuppressive medications within 14 days of planned first dose 5) Other active malignancy requiring treatment 6) Serious or uncontrolled medical disorder or active infection which would impact on the trial or affect their involvement 7) Prior treatment with anti-PD-L1, anti-PD-L2, anti-CD137 or anti-CTLA-4 antibody 8) History of testing positive for HIV or AIDS or a positive test for Hepatitis indicating acute or chronic infection 9) History of allergy or sensitivity to monoclonal antibodies 10) Women who are pregnant or breastfeeding |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is overall survival calculated from the time of randomisation to the date of death and progression free survival |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Calculated from the time of randomisation to the date of death |
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E.5.2 | Secondary end point(s) |
a) response rate b) safety/tolerability c) quality of life and cost per QALY d) sensitivity to nivolumab with presence of PD-L1 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
a) time from randomisation to progression (according to RECIST), or death from any cause (whichever event comes first).
b) Time from randomisation to best response as determined by RECIST evaluation
c) Assessed using the CTCAE criteria to review adverse events from first treatment to to 30 days after last dose
d) Sample taken at baseline for central analysis. Results collated throughout trial. |
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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 | Yes |
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) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | 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 | 25 |
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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Trial follow-up will continue for a minimum of 6 months after the last participant has progressed, or completed or discontinued treatment. The end of the trial is defined as the date of final data capture to meet the trial endpoints. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
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 | 0 |