Enzalutamide for Patients With Androgen Receptor Positive Salivary Cancers

This single arm Phase II trial will assess the best overall response associated with enzalutamide in patients with AR-positive salivary cancers. Given that this will be one of the first prospective studies ever conducted for AR-positive salivary cancers, and there are currently no standard therapies known to be effective for this disease, the investigators will adopt a best overall response (BOR) of 5% as the null hypothesis and BOR of 20 % as the alternative hypothesis. In addition to response, this study will also evaluate the progression-free survival (PFS), overall survival (OS), adverse events, and will also try to identify molecular predictors of response by examining genomic and transcriptional elements of androgen receptor biology.

The primary and secondary objectives of the study:

Primary objective

To evaluate the rate of best overall response associated with enzalutamide in patients with AR-positive salivary cancers

Secondary objectives

• To evaluate the progression-free survival (PFS) of AR-positive salivary cancer patients treated with enzalutamide
• To evaluate the overall survival (OS) of AR-positive salivary cancer patients treated with enzalutamide
• To evaluate the safety/tolerability of enzalutamide for patients with AR-positive salivary cancer

Patients are followed up to 3 years after study enrollment.

• 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.
• Disease status - Measurable disease as defined in the protocol. Locally advanced/unresectable (as determined by local surgeon) OR metastatic disease.
• 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).
• 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.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
• 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
• 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
• 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.