Background: TGCTs represent a highly curable disease, however, a small proportion of patients develop disease recurrence. Loss of the tumor suppressor gene PTEN (phosphatase and tensin homolog) marks the transition from intratubular germ cell neoplasias to invasive GCTs and correlated with disease progression. PTEN inactivation is associated with dysregulation of PI3K/Akt pathway and increased mTOR signalling. We hypothesize that dysregulation of PI3K/Akt pathway due to PTEN inactivation in GCTs suggests that these patients would have greater benefit from mTOR inhibition. This study aimed to determine of efficacy and toxicity of everolimus in refractory testicular germ cell tumors (TGCTs) Methods: From December 2011 to February 2015, 15 refractory GCTs (14 testicular, 1 primary retroperitoneal) patients were enrolled to the phase II study (clinical trial registry number NCT01466231). All patients were pretreated with at least 3 cisplatin based therapy, 3 patients (21.3%) were absolute cisplatin refractory and 8 patients (57.1%) had visceral non-pulmonary metastases at start of treatment. Everolimus was administered at a dose of 10 mg daily until progression or unacceptable toxicity. The primary endpoint was objective response rate according to RECIST. Results: Median age of patients was 35 years (range 23-52 years). No objective response was observed, 3 patients (21.4%) achieved minor response for 4.9+, 6.3 and 9.5 months including one cisplatin absolute refractory patient and additional 2 patients (14.3%) achieved prolonged disease stabilization for 8.5 and 22.2 months. In median follow-up of 4.9 months (range 1-38 months), 13 patients (92.9%) experienced disease progression and 10 patients (71.4%) died. Median progression-free survival was 1.7 months (range 1.1 - 5.3 months) and median overall survival was 6.0 months (range 2.2 – 11.8 months). Treatment was tolerated well, 2 patients experienced grade 3-4 toxicity (pneumonitis and renal failure). Conclusions: Study failed to achieve its primary endpoint and our data suggest limited efficacy of everolimus in unselected heavily pretreated refractory TGCTs, however prolonged disease stabilization could be achieved in selected patients. Clinical trial information: NCT01466231