Enzalutamide in Combination with Gemcitabine and Nab-Paclitaxel for the Treatment of Advanced Pancreatic Cancer

Inclusion Criteria

• Patients must have histologically or cytologically confirmed pancreatic adenocarcinoma that is metastatic or unresectable; in the dose expansion phase, the tumor must express AR by immunohistochemistry; if >= 1% of the tumor cells express AR, it will be considered positive for this trial
• Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Life expectancy of greater than 3 months
• Leukocytes >= 3,000/uL
• Absolute neutrophil count >= 1,500/uL
• Platelets >= 100,000/uL
• Total bilirubin =< 2 X institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 X institutional upper limit of normal (=< 5 if liver metastases present)
• Creatinine =< 1.5 X institutional upper limit of normal OR
• Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above 1.5 X institutional upper limit of normal
• International normalized ratio (INR) < 1.5 (or < 3 if on warfarin or other anticoagulants)
• Prior treatment with gemcitabine alone or 5-fluorouracil with radiation as an adjuvant therapy will be allowed; patient should not have received gemcitabine within 6 months of starting the study treatment; 5-flourouracil or radiation treatment should be received more than 4 weeks prior to receiving the study drug
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of the study treatment
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Prior treatment with any cytotoxic chemotherapy except as an adjuvant therapy; patient should not have received gemcitabine within 6 months of starting the study treatment; 5-flourouracil or radiation treatment should be received more than 4 weeks prior to receiving the study drug
• Patients may not be receiving any other investigational agents within 4 weeks of starting the study treatment and during the study period
• Untreated brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine, nab-paclitaxel or enzalutamide
• Patients who have undergone major surgery within 4 weeks prior to starting the study treatment
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; patients with a history of myocardial infarction within 6 months of starting study treatment will be excluded
• Patients with a known history of human immunodeficiency virus (HIV) infection or active hepatitis B or hepatitis C
• Any history of seizure; history of loss of consciousness or transient ischemic attack within 12 months of starting the study drug
• Any women who are pregnant or breast feeding, or women/men able to conceive and unwilling to practice an effective method of birth control
• Chronic treatment with immunosuppressant drugs
• Other malignancy requiring active treatment
• Any significant medical condition, laboratory abnormality, or psychiatric illness, that would prevent subjects from participating in the study, including the inability to swallow capsules
• Any active infection not controlled by antibiotics
• Concomitant medications that lower seizure threshold