A Prospective Study Investigating the Efficacy and Toxicity of Definitive ChemoRadadiation and ImmunOtherapy (CRIO) in Locally and/or Regionally Advanced Cutaneous Squamous Cell Carcinoma.

Abstract Background: Patients with unresectable advanced cutaneous squamous cell carcinoma (cSCC) are generally treated with palliative intent. Immune checkpoint blockade has significant activity in the palliative setting in patients with recurrent or metastatic cSCC. This single arm phase 2 prospective study aims to investigate the combination of curative intent chemoradiation and durvalumab (anti-PD-L1 checkpoint inhibitor) for this patient cohort. Our hypothesis is that >70% of patients with locally-advanced primary disease or regional metastases can be safely treated for cure using ChemoRadiation and ImmunOtherapy (CRIO) compared to the null hypothesis of ≤50%. Methods: Patients with unresectable locally and or regionally advanced pathologically confirmed cSCC deemed suitable for CRIO by consensus of the Head and Neck Multidisciplinary meeting will be eligible. We aim to accrue a total of 15 patients. The co-primary endpoints of CRIO will be the safety of treatment and the complete response rate. Secondary endpoints will include overall survival, progression free survival, and locoregional control. Translational research endpoints including biomarkers will also be explored utilising multiplex immunohistochemistry on tumour biopsy samples obtained prior to commencing treatment and during treatment (week 2). In addition, the utility of CXCR-4 PET scan will be explored.Discussion: CRIO is a novel trial evaluating the combination of curative intent chemoradiotherapy with concurrent durvalumab for patients with inoperable locally advanced cSCC.Trial registration Trial registered with the Australian New Zealand Clinical Trial Registry (ACTRN12618001573246)