Intermittent Androgen Deprivation Therapy for Stage IV Castration Sensitive Prostate Cancer

Investigators proposed this pilot feasibility study to use prostate specific antigen (PSA)
response and testosterone level to guide the treatment with androgen deprivation therapy
(ADT) [Leuprolide, Goserelin, and Triptorelin are the most commonly used GnRH agonists for
ADT] and/or abiraterone plus prednisone. Adaptive therapy is a program of chemotherapy where
the type and dosage of drug changes in an attempt to kill more of the cancer.

Abiraterone acetate with prednisone is a standard of care treatment for mCRPC (metastatic
castration resistant prostate cancer). It works by interrupting the male hormone (androgen)
making process in the testes, adrenal glands, and tumors. This helps to prevent the growth of
tumors that need these hormones to grow.

Inclusion Criteria:

- Histologically or cytologically confirmed adenocarcinoma of the prostate.

- High risk mCSPC as defined by the Latitude study5 (≥ 2 of 3 risk factors: Gleason ≥ 8,
≥ 3 bone lesions, or measurable visceral metastases)

- >75% prostate specific antigen (PSA) decline after 12 weeks of run in period with
androgen deprivation therapy (ADT), abiraterone plus prednisone.

- Performance status Eastern Cooperative Oncology Group (ECOG) 0-1

- Adequate organ function Serum alanine aminotransferase (ALT) or aspirate
aminotransferase (AST) must be < 2.5 x upper limit of normal (ULN), total bilirubin
less than 1.5 X ULN, estimated creatinine clearance must be >40 mL/min, absolute
neutrophil count (ANC) > 1500/l, hemoglobin above 9 g/dl, platelet count > 100,000/l

- Stable medical condition, including the absence of acute exacerbations of chronic
illnesses, serious infections or major surgery within 28 days prior to study
enrollment

- Ability to give written informed consent

Exclusion Criteria:

- Prior ADT with GnRH analogue for non-metastatic prostate cancer within 2 years prior
to study enrollment.

- Prior treatments with TAK-700/Orteronel, abiraterone, ketoconazole, apalutamide or
enzalutamide.

- Documented central nervous system metastases or liver metastasis

- Prior surgical castration

- Requiring opioids for cancer related pain.

- Treatment with any investigational compound within 30 days prior to the first dose of
study drugs

- Diagnosis or treatment for another systemic malignancy within 2 years before the first
dose of study drugs, or previously diagnosed with another malignancy & have any
evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in
situ of any type are not excluded if they have undergone complete resection.

- Uncontrolled hypertension despite appropriate medical therapy (blood pressure of
greater than 160 mmHg systolic and 90 mmHg diastolic at 2 separate measurements no
more than 60 minutes apart during the Screening period). Note: Patients may be
rescreened after adjustments of antihypertensive medications

- Unstable symptomatic ischemic heart disease, ongoing arrhythmias of Grade > 2 (NCI
CTCAE, version 5), New York Association Class III or IV heart failure

- Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C
not contained with anti-viral therapy, life threatening illness unrelated to cancer,
or any serious medical or psychiatric illness that could, in investigator's opinion,
potentially interfere with participation in this study.

- Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI
absorption or tolerance of study drugs, including difficulty swallowing tables.

- Delayed healing of wounds, ulcers, and/or bone fractures

- Inability to comply with protocol requirements