E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Histologically proven diagnosis of malignant pleural mesothelioma. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059518 |
E.1.2 | Term | Pleural mesothelioma malignant |
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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 |
PRIMARY: To assess the antitumor activity in terms of time to progression (TTP) of bevacizumab in combination with pemetrexed and carboplatin. |
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E.2.2 | Secondary objectives of the trial |
SECONDARY: To evaluate the objective response rate (RR) of the combination. To evaluate the toxicity and the safety profile of the combination. To evaluate the duration of response (RD) and time to treatment failure (TTF). To evaluate overall survival (OS). |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
INCLUSION CRITERIA 1. Histologically proven diagnosis of malignant pleural mesothelioma. 2. Inoperable disease according to local surgeon, not previously treated with chemotherapy; patients relapsed/progressed after previous surgery will be also evaluable for inclusion. 3. Age  18. 4. ECOG Performance Status 0-1 & life expectancy of at least 12 weeks. 5. Measurable and/or evaluable lesions according to RECIST criteria. 6. Laboratory requirements:  Neutrophils 1.5 x 109/L and Platelets 100 x 109/L  Total bilirubin 1.5 time the upper-normal limits (UNL) of the Institutional normal values, AST (SGOT) and ALT (SGPT) 2.5 x UNL, or 5 x UNL in case of liver metastases, alkaline phosphatase 2.5 x UNL,  5 x UNL in case of liver metastases, 10 x UNL in case of bone metastases.  Creatinine clearance >50 mL/min, calculated according to the Cockroft and Gault formula.  Urine dipstick of proteinuria <2+. Patients discovered to have 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate 1 g of protein/24 hr. 7. Written informed consent. 8. Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating center. |
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E.4 | Principal exclusion criteria |
1. Any prior chemotherapy for malignant pleural mesothelioma including intracavitary administration. 2. Symptomatic and/or unstable pre-existing brain metastases. 3. Serious non-healing wound or ulcer. 4. Evidence of bleeding diathesis or coagulopathy. 5. Uncontrolled hypertension. 6. Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents (6 months), myocardial infarction ( 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication. 7. Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes. 8. Chronic, daily treatment with high-dose aspirin (>325 mg/day) or other medications known to predispose to gastrointestinal ulceration. 9. Treatment with any investigational drug within 30 days prior to enrolment. 10. Patients with known allergy to Chinese hamster ovary cell proteins, or any of the components of the study medications. 11. Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ 12. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study. 13. Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
Endpoints The primary endpoint of the study will be the median progression-free survival (PFS) of bevacizumab in combination with premetrexed and carboplatin. For secondary endpoints, the response rate will be assessed with RECIST criteria; the duration of response will be evaluated from the date of achieved response to the date of progression or death, whichever comes first. Events will be considered progression or death. For censored patients, the duration will last until the latest observation date. PFS and overall survival (OS) will be evaluated from the date of patient study enrolment to the date of event (progression and death for PFS or death only for OS) or to the latest observation date for censored patients. Kaplan Mejer curves will be used for describing all these survival data. Maximum grade of toxicity experienced during treatment will be assessed with NCIC criteria and using frequencies and percentages for each type of toxicity considered. |
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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 | No |
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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 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 | 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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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 | |
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 | 0 |