Abiraterone is approved in the United States by the U.S. Food and Drug Administration (FDA) to treat metastatic prostate cancer at 1000 mg daily.

The purpose of this study is to find out if an on and off schedule of taking abiraterone would prolong the participant's cancer's response to this drug and maintain their functionality to perform their daily activities.

In this pilot study, 10 black participants and 15 non-black participants will be enrolled after achieving 50% or more decline of their prostatic specific antigen (PSA) while on abiraterone for asymptomatic or minimally symptomatic metastatic castration resistant prostate cancer (mCRPC). Abiraterone will be stopped and will not be re-initiated until there is 50% or more increase of the PSA. Each time abiraterone is stopped, it will be defined as the start of a new adaptive therapy cycle. Participants who cannot achieve a 50% decline of their PSA after restarting abiraterone will continue abiraterone until they develop radiographic disease progression. If the decline in performance status does not occur at the time of radiographic disease progression, participants will be followed until they develop radiographic disease progression.

The study will be terminated early if less than 3 of the first 10 enrolled participants can complete 2 cycles of the adaptive abiraterone.

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate (the availability archival prostate tumor sample is preferred not required)
• Asymptomatic or minimally symptomatic (not requiring opioids for cancer related pain) metastatic castration resistant prostate cancer (CRPC) patients on abiraterone as standard of care and achieved at least 50% decline of their pre-treatment prostatic specific antigen (PSA)
• Performance status Eastern Cooperative Oncology Group (ECOG) 0-2
• Adequate organ function
• Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections or major surgery within 28 days prior to study enrollment
• Prior surgical castration or concurrent use of gonadotropin-releasing hormone (GnRH) analogue (i.e. medical castration) with testosterone at screening <50 ng/dL.
• Ability to give written informed consent

Exclusion Criteria:

• Except GnRH analogue therapy, any other therapies for prostate cancer (excluding bisphosphonate and denosumab) must be discontinued 3 weeks before the first dose of study drugs.
• Prior treatments with Cyp 17 inhibitors like TAK-700/Orteronel, ketoconazole, radium 223 or docetaxel (up to 6 cycles of docetaxel given in the non CRPC setting is allowed). Prior treatment with Sipuleucel-T is allowed.
• Documented central nervous system (CNS) metastases or liver metastasis
• 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. Potential participants 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: May be rescreened after adjustments of antihypertensive medications
• Unstable symptomatic ischemic heart disease, ongoing arrhythmias of Grade > 2 [National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03], New York Heart Association (NYHA) 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