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:
To evaluate the rate of best overall response associated with enzalutamide in patients with
AR-positive salivary cancers
1. To evaluate the progression-free survival (PFS) of AR-positive salivary cancer patients
treated with enzalutamide
2. To evaluate the overall survival (OS) of AR-positive salivary cancer patients treated
3. To evaluate the safety/tolerability of enzalutamide for patients with AR-positive
Patients are followed up to 3 years after study enrollment.
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
- 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.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both