Nintedanib as Switch Maintenance Treatment of Pleural Malignant Mesothelioma

Inclusion Criteria:

* Histological diagnosis of unresectable Malignant Pleural Mesothelioma (MPM);
* Response or Stable disease according to modified RECIST criteria \[48\] after first line platinum-pemetrexed chemotherapy for 4-6 cycles;
* Last platinum chemotherapy dose administered within 60 days (i.e. randomization must occur within 60 days from the last dose of the last cycle of platinum-pemetrexed chemotherapy);
* Age \>18 years;
* ECOG performance status (PS) 0-2;
* Life expectancy of at least 12 weeks in the opinion of the investigator;
* Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of first dose

Exclusion Criteria:

* prior systemic anticancer therapy including cytotoxic therapy or immune-checkpoint inhibitor, for MPM, other than first line platinum-based doublet chemotherapy;
* previous extra-pleural pneumonectomy (other forms of previous surgery eg pleurectomy are acceptable);
* previous Vascular Endothelial Growth Factor (VEGF) inhibitors (eg bevacizumab, sorafenib, etc);
* treatment with other investigational drugs or treatment in another clinical interventional trial within the past 4 weeks before start of therapy or concomitantly with the trial;
* patients that, in the opinion of the investigator, have reduced performance status by 2 ECOG levels (e.g. PS 0 to 2 or PS 1 to 3) from beginning to completion of 1st line chemotherapy;
* radiotherapy (with the exception of palliative radiotherapy) during study or within 4 weeks of start of study drug;
* known brain metastasis or lepto-meningeal disease. Patients with suspicious neurological symptoms should undergo a CT scan/MRI of the brain to exclude brain metastasisNo active brain metastases (e.g. stable for \< 4 weeks;, no adequate previous treatment with radiotherapy;, symptomatic, requiring treatment with anti-convulsants; dexamethasone therapy will be allowed if administered as stable dose for at least one month before randomization); patients with suspicious neurological symptoms should undergo a CT scan/MRI of the brain to assess brain metastasis;
* leptomeningeal metastases;
* significant weight loss (\> 10 %) within the past 6 weeks prior to treatment in the present trial;
* pre-existing clinically significant ascites and/or clinically significant pleural effusion;
* active or history of bleeding complications that would prevent anti-angiogenic therapy
* centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels; typical mediastinal pleural involvement with mesothelioma remains eligible;
* clinically active cancer other than mesothelioma within 5 years prior to start of study treatment;
* radiographic evidence of cavitatory or necrotic tumors;
* unstoppable use of therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous device) or antiplatelet therapy (except for chronic low-dose therapy with acetylsalicylic acid =325mg per day);
* clinically significant cardiovascular diseases (i.e. hypertension not controlled by medical therapy, unstable angina, history of myocardial infarction within the past 6 months, congestive New York Heart Association (NYHA) II, serious cardiac arrhythmia, clinically significant pericardial effusion)