WEE1 Inhibitor MK-1775, Docetaxel, and Cisplatin Before Surgery in Treating Patients With Borderline Resectable Stage III-IVB Squamous Cell Carcinoma of the Head and Neck

PRIMARY OBJECTIVES: I. To evaluate the safety profile and determine a maximum tolerated dose (MTD) dose of AZD1775 (WEE1 inhibitor MK-1775) in combination with weekly cisplatin and docetaxel as a neoadjuvant approach in locally advanced borderline resectable and/or surgically unresectable with high nodal burden (e.g., \>= N2b disease) and judged appropriate for non-surgical definitive therapy. II. To determine the pharmacokinetics (PK) of the combination of single doses of AZD1775 with fixed weekly dosing of docetaxel and cisplatin given on a three out of four week cycle. III. To evaluate pharmacodynamic (PD) biomarkers of AZD1775 drug effect in head and neck squamous cell carcinoma (HNSCC) cancers, and in particular p53 mutated HNSCC patients. SECONDARY OBJECTIVES; I. To evaluate the preliminary activity and efficacy of the combination in terms of objective response rate in patients with borderline resectable and unresectable HNSCC and in particular, in p53 mutated HNSCC patients. II. The rate of resectability for borderline unresectable patients will be noted post neoadjuvant therapy. III. The rate of unresectable patients who underwent definitive therapy via chemoradiation. IV. Progression-free survival will be noted as part of the preliminary efficacy determination of this study. VI. During all parts of the study, patients will be monitored carefully for the development of adverse experiences and will be monitored for clinical and/or radiographic evidence of disease progression according to usual standards of clinical practice. TERTIARY OBJECTIVES: I. To gain mechanistic understanding of the link between p53 mutation status and disruption of immunoglobulin heavy constant gamma 2 (G2M) regulation deregulation. II. To confirm kinase inhibition in tumor primary cultures as well as in patient tumor-derived xenografted (PDX) mice extracts, downstream signaling consequences (WEE1 G2 checkpoint kinase \[WEE1\]; WEE1's target, cyclin-dependent kinase 1 \[CDC2\]), and mechanisms of p53 synthetic lethality which sensitize cancer cells to genotoxic therapy. OUTLINE: This is a dose-escalation study of WEE1 inhibitor MK-1775. Patients receive WEE1 inhibitor MK-1775 orally (PO) twice daily (BID) on days 2-4, 9-11, and 16-18, and day -7 prior to course 1, day 1 for PD assessment. Patients also receive cisplatin intravenously (IV) on days 1 (or up to two days after last dose of WEE1 inhibitor MK-1775 lead-in is completed), 8 (or 7 days after first chemotherapy dose), and 15, and docetaxel IV on days 1, 8, and 15. Patients experiencing progressive disease undergo surgical resection. Patients not deemed surgically resectable proceed to chemoradiation as clinically indicated. Patients experiencing stable disease or partial response may receive 2 additional courses of treatment every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 4 years.