E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
advanced malignant pleural mesothelioma |
|
E.1.1.1 | Medical condition in easily understood language |
a type of lung cancer that is called “malignant pleural mesothelioma” (MPM) |
|
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 | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10035605 |
E.1.2 | Term | Pleural mesothelioma malignant advanced |
E.1.2 | System Organ Class | 100000004864 |
|
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 objective of this trial is to assess the effect of atezolizumab in terms of PFS and OS when added to standard of care (carboplatin/pemetrexed/bevacizumab), as first-line treatment of advanced MPM. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate secondary measures of clinical efficacy including response rate, disease control rate, time to treatment failure, duration of response.
To assess the safety and tolerability of the treatment.
To evaluate symptom-specific and global quality of life. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically confirmed advanced malignant pleural mesothelioma (all histological subtypes are eligible)
- Able to understand and give written informed consent and comply with trial procedures
- Age >18 years
- Performance Status 0-1
- Not amenable for radical surgery based on local standards
- Availability of tumour tissue for translational research
- Evaluable disease or measurable disease as assessed according to the mRECIST v1.1
- Life expectancy >3 months
- Adequate haematological, renal and liver function (CrCl >45)
- Completed baseline QoL questionnaire
- Men and women of childbearing potential must agree to use adequate contraception |
|
E.4 | Principal exclusion criteria |
- Prior treatment for malignant pleural mesothelioma
- Active autoimmune disease that has required systemic treatment in past 2 years
- Previous history of significant haemoptysis (defined as at least 2.5mL emission of red blood) in the 3 months prior to inclusion.
- Recent surgery:
1. Major surgery or significant traumatic injury within 28 days prior to inclusion.
2. Minor surgical procedure within 7 days, or placement of a vascular access device within 2 days of randomisation.
- HIV or active hepatitis B or hepatitis C |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Co-Primary endpoints: Progression-free survival (PFS) according to the mRECIST v1.1 and overall-survival (OS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
-PFS: time from the date of randomisation until documented progression or death
-OS: time from the date of randomisation until death from any cause. |
|
E.5.2 | Secondary end point(s) |
Response rate (OR)
Disease control rate (DC)
Time to treatment failure (TTF)
Duration of response (DoR)
Adverse events according to CTCAE v5.0
Symptom-specific and global quality of life |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
-OR: from the start of protocol treatment across all time points until the end of protocol treatment
-DC: at 24 weeks.
-TTF: time from the date of randomisation to discontinuation of protocol treatment for any reason
-DoR: interval from the date of first documentation of objective response to the date of first documented progression or relapse.
-Adverse events:from the date of signature of informed consent until 90 days after the last dose of protocol treatment, regardless of whether it is considered related to a medication.
-Quality of life: from baseline to 12 weeks after treatment start. |
|
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) | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Italy |
Portugal |
Slovenia |
Spain |
Switzerland |
United Kingdom |
|
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
|
|
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 | 7 |
E.8.9.1 | In the Member State concerned days | |
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 | 7 |