Enzalutamide for Patients With Androgen Receptor Positive Salivary Cancers

Study Overview
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Brief Summary
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This study will test any good and bad effects of the study drug called enzalutamide. Enzalutamide could shrink the cancer but it could also cause side effects. Researchers hope to learn if the study drug will shrink the cancer by at least 30% compared to its present size, in at least 1 out of 5 patients. Enzalutamide is not FDA approved to treat salivary gland cancer, but it has already been FDA-approved to treat other cancers.

Detailed Description
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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.

Official Title
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A Phase II Study of Enzalutamide (NSC# 766085) for Patients With Androgen Receptor Positive Salivary Cancers

Conditions
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Salivary Cancer

Intervention / Treatment
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* Drug: enzalutamide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Enzalutamide<br>Patients receive 160 mg enzalutamide orally once daily (1 cycle=28 days). Patients will remain on therapy until progression of disease or development of unacceptable toxicities or patient or physician withdrawal. Patients will undergo radiographic imaging every 2 months while on study treatment in order to determine response. | Drug: enzalutamide<br>* oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response Rate | The best overall response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients. | Up to 32 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | Up to 32 months post study enrollment | 
| Number of Patients Experiencing at Least One Grade 3+ Adverse Event Using CTCAE Version 4.0 | The number of patients experiencing at least one grade 3+ adverse event using CTCAE version 4.0 is summarized below. | 30 days post-treatment, up to 32 months |