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.