Transdermal Testosterone and Enzalutamide in Treating Patents with Castration Resistant Prostate Cancer Receiving Androgen Deprivation Therapy

Inclusion Criteria

• Provision to sign and date the consent form.
• Male and age ≥ 18 years old
• Stated willingness to comply with all study procedures and be available for the duration of the study.
• Histologically or cytologically proven adenocarcinoma of the prostate.
• Ongoing antiandrogen therapy (ADT) for prostate cancer with a GnRH analogue/antagonist or bilateral orchiectomy for at least 6 months prior to day 1.
• Patients on a first generation anti-androgen (e.g. bicalutamide, flutamide, nilutamide) must have at least a 6-week washout prior to randomization and must show continued PSA progression.
• Serum testosterone level < 50 ng/dL at the screening visit.
• Progressive disease at screening as defined by one or more of the following criteria: * PSA progression: minimum of 2 rising values within an interval of > 1 week between values. And a value at screening of > 1 ng/mL * Soft tissue progression on CT or MRI based on RECIST 1.1 criteria or progression of bone disease according to PCWG3 criteria.
• Absolute neutrophil count >= 1000/uL (at screening).
• Platelet count >= 100,000/uL (at screening).
• Hemoglobin >= 8 g/dL (at screening).
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (unless documented Gilbert’s) (at screening).
• Alanine aminotransferase or aspartate aminotransferase =< 2.5 x ULN (at screening).
• Glomerular filtration rate > 30 mL/min (at screening).
• Hemoglobin =< 17.5 g/dL (at screening).
• Evidence of metastatic disease at any time point on axial imaging or bone scan, or previous biopsy. Stage IV pelvic lymph node involvement is acceptable.
• Must use a condom if having sex with a pregnant woman.
• A male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration.
• Patients may have received any number of lines of therapy for castration resistant disease.

Exclusion Criteria

• Clinically significant cardiovascular disease as evidenced by any of the following: * Myocardial infarction with 6 months of screening * Uncontrolled angina within 3 months of screening * New York Heart Association (NYHA) class 3 or 4 congestive heart failure * Clinically significant ventricular arrhythmia * Mobitz II/second degree/or 3rd degree heart block without a pacemaker in place; uncontrolled hypertension (HTN) (systolic >180 mmHg or diastolic >105 mmHg at screening.
• Previous exposure to a second-generation anti-androgen i.e enzalutamide or apalutamide.
• Received investigational agent within 2 weeks of screening.
• Therapy with antineoplastic systemic chemotherapy or biological therapy within 2 weeks of screening.
• Radiation therapy within 2 weeks of screening.
• History of a prior malignancy (excluding an adequately treated basal or squamous cell skin cancer, superficial bladder cancer, or a cancer in situ) within 5 years prior to study enrollment.
• History of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agent.
• Known or suspected brain metastasis or active leptomeningeal disease.
• History of seizure at any time in the past. Also, history of loss of consciousness or transient ischemic attack within 12 months of Day 1 visit.
• Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements.