Background: Since standard chemotherapy treatment does not lead to long-term survival, new treatment approaches are required. MPM is known for a high vessel count and high levels of vascular growth factors. Suppression of the neo-vasculature by adding the oral VEGF-TKI axitinib to standard chemotherapy may lead to improvement. This study had both clinical and translational objectives. We here report the secondary endpoints response, PFS, OS and toxicity. Methods: Treatment naïve patients with suspected or proven malignant mesothelioma and medically suitable for limited surgical intervention were eligible after informed consent. Patients were treated with pemetrexed (500mg/m²q3wk) and cisplatin (75mg/m²q3wk) and were randomised to daily axitinib (2x5mg tablets). Before treatment a thoracosopy was performed to confirm the diagnosis. After 3 cycles of chemotherapy a palliative pleurectomy was performed. During both interventions material was obtained for research purposes. Patients could receive an additional 2 cycles of chemotherapy. Results: From July 2009 until October 2012, 26 patients were randomised. Six consecutive patients who received chemotherapy plus axitinib to demonstrate the feasibility and safety of the study design, were also included. In total twenty patients received axitinib. There was one protocol violation in the control arm. Median age: 61 yrs (35 yrs – 75 yrs), 84% epithelial type, 94% WHO 0-1 and 6% WHO 2. Median follow up was 18 months. Toxicity: There was more grade 3, 4 toxicity in the axitinib group concerning neutropenia (40% vs. 9%; p=0.11). One patient in the axitinib group developed a CVA, one patient pulmonary emboli. No thromboembolic events occurred in the control arm. Partial response was observed in 35% of patients in the experimental arm vs. 27% in the control group (p=0.99). Median PFS was 8 months in the experimental arm vs. 8.3 months in the control arm. There was also no difference in overall survival 17 vs 18 months, respectively. Conclusions: Axitinib was well tolerated in combination with cisplatin and pemetrexed. There was no evidence of benefit in response rate, progression free or overall survival. Clinical trial information: NCT01211275.