Oral Testosterone Undecanoate Followed by Enzalutamide for the Treatment of Metastatic Castration Resistant Prostate Cancer, The AcroBAT Study

Inclusion Criteria

• Performance status ≤ 2
• Age ≥ 18 years
• Histologically-confirmed adenocarcinoma of the prostate
• Evidence of metastatic, measurable disease by CT scan. Measurable disease is defined by RECIST 1.1 as at least one measurable lesion ≥ 10mm by CT scan
• Progressing on first line therapy with either continuous androgen deprivation therapy (ADT) (either surgical castration or luteinizing hormone-releasing hormone [LHRH] agonist/antagonist) alone, or ADT in combination with bicalutamide or next generation androgen receptor inhibitors (abiraterone, enzalutamide, darolutamide)
• Documented castrate level of serum testosterone (< 50 ng/dl)
• Patients progressing on combination therapy will continue ADT but must be off anti-androgen or abiraterone for 4 weeks prior to first treatment with OT
• Patients receiving prednisone in conjunction with abiraterone acetate must be weaned off prednisone if possible prior to starting OT. Patients who cannot be weaned entirely off prednisone must be maintained on lowest stable dose that relieves symptoms
• Rising PSA on two successive measurements at least two weeks apart. Screening PSA must be ≥ 1.0 ng/mL
• Patients must continue on castrating therapy throughout OT treatment
• Prior docetaxel for castration-sensitive prostate carcinoma (CSPC) is permitted if ≤ 6 doses were given in conjunction with first-line androgen deprivation therapy and > 6 months since last dose of docetaxel
• Bilirubin < 2.5 times institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) < 2.5 times ULN
• Serum creatinine < 2.5 times ULN
• Absolute neutrophil count (ANC) ≥ 1500 cells/mm^3 (1.5 x 10^9/L)
• Platelet count ≥ 100,000 platelet/mm^3 (100 x 10^9/L)
• Hemoglobin ≥ 9 g/dL
• At least 4 weeks since prior surgery with full recovery (no persistent toxicity ≥ grade 1)
• Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

• Pain due to metastatic prostate cancer requiring opioid analgesics
• Prior treatment with any agent (such as docetaxel, cabazitaxel, anti-androgen, abiraterone, or investigational agent) for metastatic castration-resistant prostate cancer is prohibited
• Requires urinary catheterization for voiding due to obstruction secondary to prostatic enlargement thought to be due to prostate cancer or benign prostatic hyperplasia. Patients with indwelling catheter/suprapubic catheter to relieve obstruction are eligible
• Evidence of disease in sites or extent that, in the opinion of the investigator, would put the patient at risk from therapy with testosterone (e.g. femoral metastases with concern over fracture risk, epidural spinal metastases with concern over spinal cord compression, lymph node disease with concern for ureteral obstruction)
• Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study
• Active uncontrolled infection, such as HIV/AIDS or chronic hepatitis B or untreated chronic hepatitis C
• Prior history of a thromboembolic event within the past two years and not currently on systemic anticoagulation
• Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment
• Stroke (including transient ischemic attack), myocardial infarction, or other symptomatic ischemic event
• Significant cardiovascular disease (such as New York Heart Association class II or greater cardiac disease, unstable arrhythmia, or unstable angina) within 6 months prior to initiation of study treatment
• History of clinically significant ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing)
• Patients on coumadin must be switched to alternative anticoagulation. Patients receiving anticoagulation therapy with warfarin, rivaroxaban or apixaban are not eligible for study. Patients on enoxaparin or edoxaban are eligible for study. Patients on warfarin, rivaroxaban or apixaban, who can be transitioned to enoxaparin prior to starting study treatments, will be eligible
• Hematocrit > 50%, untreated severe obstructive sleep apnea, uncontrolled or poorly controlled heart failure (per Endocrine Society Clinical Practice Guidelines)