Everolimus in patients with multiply relapsed or cisplatin refractory germ cell tumors: results of a phase II, single-arm, open-label multicenter trial (RADIT) of the German Testicular Cancer Study Group

Background Treatment options for patients (pts) with multiply relapsed or refractory metastatic germ cell cancer (GCC) are limited. The mTOR inhibitor everolimus has been approved for the treatment of different solid tumors and was assessed in refractory GCC within this phase II RADIT trial of the German Testicular Cancer Study Group. Methods GCC pts progressing during cisplatin-based salvage chemotherapy, or relapsing after high-dose chemotherapy, or failing at least two lines of cisplatin-based chemotherapy were eligible. Prior combination chemotherapy with gemcitabine, oxaliplatin and paclitaxel, or a doublet combination of these drugs was mandatory. Primary endpoint was the progression-free survival rate at 12weeks. Twenty-five evaluable pts were needed, assuming a 20% two-sided type 1 error and 95% power to reject the null hypothesis of 5% of patients being progression-free after 12weeks. At least one pt among the first 13 pts being progression-free after 6weeks was mandatory to complete recruitment. Secondary endpoints were objective response rate, disease control rate (SD+PR+CR), median progression-free survival (PFS), median overall survival (OS), and safety. The trial was registered at http://clinicaltrials.gov as NCT01242631. Results Twenty-five pts from six German centers were treated with everolimus 10 mg orally once daily until disease progression or unacceptable toxicity between December 2010 and January 2014. 12-week PFS rate was 0%, no objective responses were achieved, and only one pt had stable disease after 6weeks on treatment as a prerequisite of completing patient accrual accounting for a 6-week disease control rate of 5.4%. Median PFS and OS were estimated at 7.4 weeks and 8.3 weeks, respectively. Toxicity was acceptable, with one treatment discontinuation due to adverse events, and no new safety signals detected. Conclusions Targeting the mTOR pathway with single-agent everolimus failed to produce clinically relevant responses in pts with heavily pretreated and/or cisplatin-refractory GCC.