Testosterone Therapy in Castration Resistant Prostate Cancer

Prior treatment

• 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

Other illness

• Requires urinary catheterization for voiding due to obstruction secondary to prostatic enlargement that is well documented to be due to prostate cancer or benign prostatic hyperplasia
• Evidence of disease in sites or extent that, in the opinion of the investigator, would put the patient at risk from therapy with testosterone due to a potential tumor flare (e.g. high-risk bone lesions which may result in fracture or spinal cord compression
• 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
  • 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 HTN (systolic \>180mmHg or diastolic \>105mmHg at 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

• Provision to sign and date the consent form
• Male and age \> or = 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 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 \<50ng/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 \>1ng/mL
  • Soft tissue progression on CT or MRI based on RECIST 1.1 criteria or progression of bone disease according to PCWG3 criteria
• Patients worst pain in the last 24 hours must rank less than 4 on a 0-10 scale and patients cannot be on daily narcotic medications to treat cancer-related pain. This assessment must occur within the screening window and be documented in the patient's medical record.
• Acceptable Clinical laboratory values at Screening Visit which include:
  • Absolute neutrophil count ≥ 1000/uL; platelet count ≥ 100,000/uL, hemoglobin ≥ 8g/dL
  • Total bilirubin ≤ 1.5xULN (unless documented Gilbert's); alanine aminotransferase or aspartate aminotransferase ≤ 2.5xULN
  • Creatinine ≤ 2mg/dL
  • Hemoglobin ≤ 17.5 g/dL
• 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