Our hypothesis is that the addition of bevacizumab to the standard chemotherapy treatment of MPM will improve overall survival and quality of life beyond that achieved with chemotherapy alone.

A phase II trial associating the reference chemotherapy (pemetrexed plus cisplatin) with bevacizumab is needed to ensure that no specific toxicity is induced by this association, and that this triplet have interesting activity. As pleural mesothélioma is a rare tumor, a phase III trial, using the survival data from the phase II part study, will be able to include a sufficient number of patients, in a reasonable period of time, to answer the question of efficacy of the anti-angiogenic triplet, providing the efficacy outcomes could be considered as favorable, at the end of the phase II part of the study.

• Drug: Standard Chemotherapy (Pemetrexed and Cisplatin)
• Drug: Standard Chemotherapy (Pemetrexed and Cisplatin) + Bevacizumab

• Active Comparator: Standard Chemotherapy
• Experimental: Standard Chemotherapy + bevacizumab (Avastin)

Inclusion Criteria:

• Malignant, histologically proved, non resectable pleural Mesothelioma
• In case of pleural effusion, a talc pleurodesis, although not recommended, is allowed in accordance with current local practice, at the time of diagnostic thorascopy, with inclusion CT scan performed after pleurodesis.
• ECOG Performance status 0-2
• Mesothelioma with only pleural effusion without uni- or bidimensionally measurable disease will be eligible (adapted RECIST criteria)
• At least 18 years of age, less than 76 years of age
• Radiation therapy of thoracocentis tract (3 x 7Gy) performed before beginning medical study treatment, and the interval between thoracoscopic procedure and radiation will not exceed 28 days

Exclusion Criteria:

• Prior chemotherapy
• Brain metastasis
• History of cerebral vascular accident (CVA) or transient ischemic attack

• University Hospital, Caen
• Groupe Francais de Pneumo-Cancérologie
• European Lung Cancer Working Party