Testing Two Oral Drugs Combination (Cediranib and Olaparib) Compared to a Single Drug (Olaparib) for Men With Advanced Prostate Cancer

Inclusion Criteria

• •Patients must have histologically confirmed progressive, metastatic castration resistant prostate adenocarcinoma by meeting ALL the following:
• •* Pathology of prostate gland or metastatic disease must confirm the diagnosis of prostate adenocarcinoma; mixed histology with other variants including but not limited to small cell or neuroendocrine differentiation must be discussed with the study principal investigator (PI)
• •* Metastasis must be documented by radiographic evidence
• •* Castration resistance must be documented with surgical or medical castration with serum testosterone \< 50 ng/dL (\< 2.0 nM); if the patient is being treated with luteinizing hormone-releasing hormone (LHRH) agonists (patient who has not undergone orchiectomy), this therapy must have been initiated at least 4 weeks prior to cycle 1, day 1 and must be continued throughout the study
• •* Progression must be evidenced and documented by any of the following parameters
• •* Two consecutively rising PSA values, above the baseline, at a minimum of 1-week intervals; the minimal value to enter the study is 1.0 ng/ml or greater; the reference value (#1) is the last PSA measured before increases are documented, with subsequent values obtained a minimum of 1 week apart; if the PSA at time point 3 (value #3A) is greater than that at point 2, then eligibility has been met; if the PSA is not greater than point 2 (value #3B), but value #4 is, the patient is eligible assuming that other criteria are met, if values 3A or #4 are 1 ng/mL or higher (Prostate Cancer Working Group 3)
• •* Appearance of one or more new lesions on bone scan
• •* Progressive disease by RECIST 1.1
• •Must have a tumor lesion safely accessible for biopsy per the investigator's discretion; while a soft tissue metastasis is preferred for a biopsy, a bone metastasis is allowed for biopsy as long as enough cores can be obtained; a biopsied lesion cannot be used for target lesion for response assessment
• •Must be agreeable to the mandatory research tumor biopsies (pre-treatment and on-treatment); tumor biopsies are mandatory at pre-treatment and at on-treatment; there is an optional biopsy at post-progression
• •Must have received at least one prior line of therapy for mCRPC; a taxane chemotherapy administered for metastatic castration sensitive disease will not count, unless patient develops disease progression within 12 months from the last dose chemotherapy
• •Must have a life expectancy greater than or equal to 16 weeks
• •If patient is currently on prednisone or other corticosteroids for palliation, the dose must be less than or equal to 10 mg a day or its equivalent dose and it must have been started at least 4 weeks prior to cycle 1 day 1
• •Patients must have measurable disease by RECIST v1.1, or evaluable disease with bone metastases demonstrated by Tc99 bone scan; patients with bone metastases only are allowed (NOTE: nodes \>= 1.5 cm (not \>= 2 cm) in the short axis are considered measurable, per The Prostate Cancer Working Group 3 \[PCWG3\])
• •Toxicities of prior therapy (except alopecia) should be resolved to =\< grade 1 as per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0; patients with long-standing stable grade 2 neuropathy or others (e.g., adrenal insufficiency or hypothyroidism on stable doses of replacement therapy) may be allowed after discussion with the study principal investigator (PI)
• •Age \>= 18 years. There is no dosing or adverse event data currently available on the use of cediranib or olaparib in patients \< 18 years of age, thus excluding them from enrollment
• •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky \>= 70%)
• •White blood count (WBC) \> 3 x 10\^9/L (within 28 days prior to administration of study treatment)
• •Absolute neutrophil count \>= 1,500/mcL (within 28 days prior to administration of study treatment)
• •Platelets \>= 100,000/mcL (within 28 days prior to administration of study treatment)
• •Hemoglobin \>= 10 g/dL with no pack red blood cell transfusion in the past 28 days (within 28 days prior to administration of study treatment)
• •Creatinine clearance \>= 51 mL/min, calculated using Cockcroft-Gault formula (within 28 days prior to administration of study treatment)
• •Urine protein: creatinine ratio (UPC) of =\< 1 (within 28 days prior to administration of study treatment)
• •Total bilirubin =\< 1.5 x the institutional upper limit of normal (ULN) (within 28 days prior to administration of study treatment)
• •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) \< 3 times institutional ULN unless liver metastases are present in which case they must be \< 5 x ULN (within 28 days prior to administration of study treatment)
• •Coagulation parameters (international normalized ratio \[INR\] and activated partial thromboplastin time \[aPTT\]) within 1.25 x ULN institutional limits, except where a lupus anti-coagulant has been confirmed, or except patients on anticoagulation (within 28 days prior to administration of study treatment)
• •Patients must be able to swallow oral medications and not have gastrointestinal illnesses that would preclude absorption of cediranib or olaparib
• •Adequately controlled thyroid function, with no symptoms of thyroid dysfunction; patients can be on thyroid hormone replacement medication; asymptomatic patients with elevated thyroid-stimulating hormone (TSH) with normal T4/T3 are allowed to enroll, and recommended to follow with routine thyroid function test especially if they are randomized to cediranib/olaparib arm
• •Adequately controlled blood pressure (BP) \< 140 mmHg (systolic) and \< 90 mmHg (diastolic) taken in the clinic setting by a medical professional within 2 weeks prior to starting study; patients with hypertension may be managed with up to a maximum of 3 antihypertensive medications; patients who are on 3 antihypertensive medications are highly recommended to be followed by a cardiologist or blood pressure specialist for management of BP while on protocol
• •Patients must be willing and able to check and record daily blood pressure readings when randomized to cediranib containing arm
• •Patients must have documented left ventricular ejection fraction (LVEF) by echocardiogram greater than institution's lower limit of normal (or 55% if threshold for normal not otherwise specified by institutional guidelines) obtained within 3 months prior to registration if they have any of the following risk factors for cardiac toxicities:
• •* A New York Heart Association (NYHA) classification of II controlled with treatment
• •* Prior central thoracic radiation therapy (RT), including RT to the heart
• •* History of myocardial infarction within 12 months prior to registration
• •* Prior treatment with anthracyclines
• •* Prior treatment with trastuzumab
• •* Prior history of other significant impaired cardiac function
• •Male participants and their female partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination (see below for acceptable methods), and not to donate sperm, throughout the period of taking study treatment and for 3 months after last dose of study drug(s) to prevent pregnancy in a partner; acceptable methods of contraception to be used in this study include:
• •* Condom with spermicide and one of the following:
• •* Oral contraceptive or hormonal therapy (e.g. hormone implants)
• •* Placement of an intra-uterine device
• •* Acceptable non-hormonal birth control methods include:
• •* Total sexual abstinence; abstinence must be for the total duration of the study and the drug washout period
• •* Vasectomized sexual partner plus male condom; with participant assurance that partner received post-vasectomy confirmation of azoospermia
• •* Tubal occlusion plus male condom with spermicide
• •* Intrauterine device (IUD) plus male condom+spermicide; provided coils are copper-banded
• •* Acceptable hormonal methods:
• •* Etonogestrel implants (e.g., Implanon, Norplan) + male condom with spermicide
• •* Normal and low dose combined oral pills + male condom with spermicide
• •* Norelgestromin/ethinyl estradiol (EE) transdermal system + male condom with spermicide
• •* Intravaginal device + male condom with spermicide (e.g., EE and etonogestrel)
• •* Cerazette (desogestrel) + male condom with spermicide; cerazette is currently the only highly efficacious progesterone based pill
• •Ability to understand and the willingness to sign a written informed consent document