A Phase II Trial of Tadalafil in Patients With Squamous Cell Carcinoma of the Upper Aero Digestive Tract

Head and neck squamous cell carcinoma (HNSCC) is a lethal solid malignancy with 5 year survival estimates of approximately 50%, and is associated with a high rate of systemic immune impairment as well as evasion of a tumor specific immune response. Preclinical and clinical data have shown that phosphodiesterase 5 (PDE5) inhibitors (tadalafil) can be used to augment immune function in HNSCC patients through inhibition of the cancer-induced myeloid derived suppressor cells (MDSCs). A multi site phase II, randomized, prospective, biomarker endpoint trial to determine optimum timing and design of PDE5 antitumor immunotherapy (tadalafil) in conjunction with conventional therapy for HNSCC. 40 patients with biopsy proven HNSCC will be randomized to receive tadalafil (n=25) or placebo (n=15) for at least 10-14 days before starting conventional therapy and continuing until 90 days after completion of conventional therapy. Tumor-specific T cell responses will be assessed using HNSCC cell lines, in blood collected before initiation of tadalafil/placebo and at 60 and 90 days after completion of conventional therapy. Number and function of MDSC and Treg cells will be assessed before and at 60 and 90 days after completion of conventional therapy. Prevnar 13® vaccine will be administered 10-14 days after commencing tadalafil/placebo (before conventional therapy begins) and again at 60 days after completion of conventional therapy. Vaccine-specific responses assessed at 60 and 90 days post-conventional therapy will be used to measure the ability of tadalafil to augment immune response to vaccine.