Enzalutamide for Patients With Androgen Receptor Positive Salivary Cancers

1. Documentation of Disease - Histologic Documentation: Histologically proven diagnosis of salivary cancer by central pathology review. Receptor status: AR expression detected by immunohistochemistry by central review. 2. Disease status - Measurable disease as defined in the protocol. Locally advanced/unresectable (as determined by local surgeon) OR metastatic disease. 3. Prior Treatment * Any number of prior lines of therapy * No treatment with biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy, or radiation ≤ 28 days before study registration. No treatment with nitrosourea or mitomycin ≤ 42 days before study registration * No prior therapy with enzalutamide (previous chemotherapy and/or other AR-targeted approaches is allowed). 4. Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. A female of childbearing potent is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (ie, has had menses at any time in the preceding 12 consecutive months). For women of childbearing potential only, a negative pregnancy test done ≤ 5 days prior to registration is required. 5. Age ≥ 18 years 6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 7. No History of the following: * prior brain metastases * leptomeningeal disease * seizures * class 3 or 4 congestive heart failure * uncontrolled hypertension (systolic BP \> 170 mmHg or diastolic BP \> 105 mmHg) * major surgery ≤ 4 weeks of registration 8. Required Initial Laboratory Values: * Absolute Neutrophil Count (ANC) ≥ 1,500/mm3 * Platelet Count ≥ 100,000/mm3 * Creatinine ≤ 1.5 x ULN Upper Limit of Normal (ULN) OR * Calculated Creatinine Clearance ≥ 30 mL/min * Total Bilirubin ≤ 1.5 x ULN * AST/ALT ≤ 3.0 x ULN 9. Concomitant medications- Chronic concomitant treatment with strong CYP2C8 inhibitors is not allowed. Patients must discontinue the drug ≥ 14 days prior to registration. Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug ≥ 14 days prior to registration.