Durvalumab, Cetuximab and Radiotherapy in Head Neck Cancer — DUCRO-HN  

Head and Neck Neoplasms Clinical Trial

Official title: Anti PD-L1 Durvalumab Combined With Cetuximab and Radiotherapy in Locally Advanced Squamous Cell Carcinoma of the Head and Neck: a Phase I/II Study

Status Not yet recruiting

Clinical Trial Summary

In over 60% of cases, squamous cell carcinoma of the head and neck (SCCHN) is discovered at a loco-regionally advanced stage that requires a combined multimodal strategy in order to pursue a curative intent. Bonner et al demonstrated that the combination of radiation (RT) with Cetuximab (CTX), a chimeric mouse IgG1 monoclonal anti-EGFR antibody, results in better median locoregional control and overall survival compared with RT alone without an increased rate of > G3 acute toxicity or detrimental effect on compliance and quality of life. However, subsequent negative trials (RTOG 0522) led to the hypothesis that in unselected patient populations the benefit of CTX may be diluted due to the molecular heterogeneity of SSCHN. Moreover, the absence of biomarkers predictive of response to anti-EGFR treatment may in part be explained by the observation that other factors play a role in favoring its anticancer effect, namely immunologic mechanisms. It has been demonstrated that SCCHN is an immunosuppressive disease characterized by prominent immuno-escape mechanisms, such as induction of a tumor-permissive cytokine profile and qualitative/quantitative lymphocyte deficiencies, occurrence of anergy in major immune effector cells and poor antigen presentation. Given these observations, it has been postulated that SCCHN may benefit from immunotherapeutic strategies, primarily aimed at PD-L1/PD1 checkpoint blockade. Segal et al (Asco 2015) reported preliminary results on the use of Durvalumab in pretreated patients with recurrent/metastatic SCCHN. Durvalumab is a humanized monoclonal IgG1 antibody that blocks PD-L1 binding to PD-1 and CD80 with high affinity and selectivity, thereby promoting activity of tumor-specific effector T cells and global anti-tumor immune response. Out of 64 treated patients, 51 patients were available for the preliminary efficacy analysis: promisingly, the overall response rate was 12% (25% in PD-L1 positive patients). To date, no clinical trial, specifically designed for SCCHN, testing PD-L1 targeted agents has been completed, nor have been initiated combination strategies of CTX, RT and PD1/PD-L1 antibodies in the curative setting. Taken all data together, a strong rationale may support the combination of Durvalumab, anti-EGFR therapy such as CTX and RT in order to revert the SCCHN-induced immune suppression and maximize treatment efficacy, ultimately through enhanced, CTX-mediated immune mechanisms and maximized RT-specific cytotoxicity.

Clinical Trial Description

n/a

Related Conditions & MeSH terms

• Head and Neck Neoplasms

• NCT number: NCT03051906
• Study type: Interventional
• Source: Azienda Ospedaliero-Universitaria Careggi
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: January 2018
• Completion date: January 2025