Ontology highlight
ABSTRACT: Introduction and background
Head and neck squamous cell carcinoma (HNSCC) has been increasingly recognized as an immune suppressive malignancy. The efficacy of immune checkpoint inhibitors (ICI's) in the context of recurrent/metastatic (R/M) setting anticipates the possible integration of immunotherapy into the therapeutic armamentarium of locally advanced disease. Durvalumab (DUR) is a humanized monoclonal IgG1, anti-PD-L1 antibody with promising data in R/M HNSCC. The aim of our study is to test the antitumor activity of a combined regimen incorporating an immune checkpoint inhibitor into a conventional bio-radiation strategy for the cure of unfavorable locally advanced HNSCC.Methods/design
In this open label, multi-center, single-arm, phase I/II study, enrolled patients will receive Radiotherapy (RT) (69.9?Gy/2.12?Gy in 33 fractions) with concurrent Cetuximab (CTX) (400?mg/m2 1?week before RT start followed by 250?mg/m2 weekly) and DUR (fixed dose of 1500?mg every 4?weeks starting from RT-CTX week 1) followed by adjuvant DUR (to a maximum of 6?months after completion of RT-CTX). Primary endpoint of the study is 2-year progression-free survival (PFS). A safety run-in is planned after the enrollment of first 12, 24 and 36 patients. Patients affected by high-risk (?N2a or??T3, any N) larynx, hypopharynx and HPV negative oropharynx or HPV-positive oropharynx (?T2, ?N2b, ?10?pack/years) will be eligible.Discussion
Conventional intensification strategies failed to provide any benefit for the cure of locally advanced HNSCC. For the still prevalent HPV-negative population and the high risk-HPV positive disease, there is an unmet need for alternative treatment paradigms. Potentially, the inhibition of the PD-1/PD-L1 checkpoint may synergize with both CTX and RT through immunologic interplay, ultimately aiming to reverse the HNSCC-induced immune suppression. The DUCRO study will seek to demonstrate if such a strategy may be safe and active.Trial registration
NCT number: NCT03051906Eudract number: 2016-004668-20.
SUBMITTER: Bonomo P
PROVIDER: S-EPMC5862684 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
Bonomo Pierluigi P Desideri Isacco I Loi Mauro M Mangoni Monica M Sottili Mariangela M Marrazzo Livia L Talamonti Cinzia C Greto Daniela D Pallotta Stefania S Livi Lorenzo L
Clinical and translational radiation oncology 20180207
<h4>Introduction and background</h4>Head and neck squamous cell carcinoma (HNSCC) has been increasingly recognized as an immune suppressive malignancy. The efficacy of immune checkpoint inhibitors (ICI's) in the context of recurrent/metastatic (R/M) setting anticipates the possible integration of immunotherapy into the therapeutic armamentarium of locally advanced disease. Durvalumab (DUR) is a humanized monoclonal IgG1, anti-PD-L1 antibody with promising data in R/M HNSCC. The aim of our study ...[more]