FRRB Project 3421802 - Neoadjuvant pembrolizumab plus chemotherapy in locally advanced sinonasal carcinoma
The Coordinator of the project is Istituti Clinici Scientifici Maugeri SpA SB. The Lead Principal Investigator of the project is Dr. Laura Deborah Locati.
| Pathology: | Advanced sinonasal epithelial tumors |
| Tematica Area: | Rare Tumors |
| Project Start Date: | TBD |
| Project End Date: | / |
| Funding: | € 482.176,00 (co-funded) |
| Project Partners: | - Istituti Clinici Scientifici Maugeri SpA SB - Fondazione IRCCS Nazionale dei Tumori - Centro Nazionale di Adroterapia Oncologica - ASST Spediali Civili di Brescia |
PROJECT SUMMARY
Advanced sinonasal epithelial tumors (SNCs) are rare head and neck cancers (HNC), account for 3-5% of HNC and 0.2-0.8% of all malignant tumors. Prognosis is dismal, with a 5-year reported PFS less than 15%. In 2020, two Italian trials have been completed in SNCs, resectable (NCT02099175) and unresectable cases (NCT02099188). All patients (pts) were managed by a multidisciplinary treatment strategy, including the employ of heavy ions radiotherapy. Response to induction chemotherapy (IC) has emerged as the most important prognostic factor for pts outcome in both trials, especially for undifferentiated sinonasal carcinoma (SNUC). These latter are enriched by CD8+ effector memory cells and characterized by the activation of immune response pathway, supporting the use of immunotherapy. In addition, a study in silico in 22 SNUC pts showed that 77.3% had benefited from protons over photons. We would maximize the activity of immunotherapy along with protons, proposing a phase II trial with neoadjuvant pembrolizumab plus chemotherapy in locally advanced SNUC pts followed by surgery [for those resectable responding less than 50% to neoadjuvant new regimen (NNR)], concomitant cisplatin-protons and adjuvant pembrolizumab. Primary hypothesis will be to test non-inferiority of the NNR compared to IC in previous trials. A sample of 28 pts achieves 80% power to detect a non-inferiority proportion (P0) of 0.50 using a one-sided binomial test for non-inferiority.