Targeting the Tumor Microenvironment in R/M SCCHN

Phase I - II trial of the combination of cyclophosphamide, RT, and Avelumab in relapsed/metastatic HNSCC (R/M-HNC). Patients pretreated with at least one line therapy containing platinum, fluorouracil, and Cetuximab. Treatment consists of metronomic cyclophosphamide 50 mg daily without drug free break, avelumab 10 mg/kg d1 and 15 q 29, and radiotherapy in one or three daily fractions up to 8 Gy maximum dose, starting at day 8. The aim of the study is to reverse tumor immune-escape by: 1. Provide a self-vaccination with radiotherapy 2. Inhibit the immunosuppressive CD4+ CD25+ FoxP3+ Treg cells with metronomic cyclophosphamide 3. Reactivate the effector T cell by the inhibition of PD-1 - PD-L1 axis with avelumab. Due to the supposed biological effects of the present trial, an ancillary translational study is needed and will be extended to all the patients' population enrolled.