BrUOG 337: Olaparib Prior to Radical Prostatectomy For Advanced Prostate Cancer Defects in DNA Repair Genes

Inclusion Criteria: * Biopsy confirmed adenocarcinoma of the prostate. * High risk for recurrence after prostatectomy including any of the following * Lymph node involvement by radiographic criteria * T3 or T4 disease by radiographic criteria * T2 disease and either PSA \> 20 or Gleason 8,9 or 10 * Defects in any of the following genes:BRCA1, BRCA 2, ATM, CHEK1, CHEK2, FANCONIS ANEMIA (FANCL), HDAC2, PALB2, BARD1, BRIP1, CDK12, PPP2R2A, RAD51B, RAD51C, RAD51D, or RAD54L as assessed by Foundation Medicine FoundationOne assay on tumor tissue or cell-free DNA from peripheral blood via the FoundationACT assay. * No distant visceral metastases. * No prior chemotherapy or radiation for prostate cancer or PARP inhibitor. Prior and current hormone therapy (\< 6 months from start date on study) for prostate cancer is allowed. Patients are allowed to remain on hormone therapy on study. * ECOG performance status 0-1. * Age\>18. * Required entry laboratory parameters * ANC≥ 1,500 cells/mm3; * Hemoglobin \> 10.0g/dL with no blood transfusion in the last 14 days * Platelet count ≥100 x 109/L, * Total bilirubin ≤ 1.5 x ULN, * AST and ALT ≤ 2.5 x ULN * Patients must have creatinine clearance estimated using the Cockcroft-Gault equation of ≥51 mL/min * Life expectancy of at least 1 year as documented by treating physician. * All Men must be willing to consent to using two highly effective contraception while on treatment and for at least 4 months (120 days) after last treatment on study * Signed study-specific consent form prior to study entry. * Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations- to be documented and submitted to BrUOG. * Formalin fixed, paraffin embedded (FFPE) tumor sample from the primary cancer must be available for central testing coordinated by Rhode Island Hospital pathology. If there is not written confirmation of the availability of an archived tumor sample prior to enrollment the patient is not eligible for the study. Submit this written certification to BrUOG * Patient agreed to not receiving any live virus and live bacterial vaccines while receiving study medication and during the 30 day follow up period. Patient should be made aware of this and it should be documented to BrUOG. * Patient agreed to not consume grapefruit juice while on study treatment. Submit documentation patient was instructed and agreed. Exclusion Criteria: * Participation in another clinical study with an investigational anticancer product during the last 2 months (from day 1 of treatment on this trial). This pertains to treatment no trials the patient may only be seen in follow-up. * Any previous treatment with PARP inhibitor for this or another cancer, including olaparib. * Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer or other solid tumors including lymphomas (without bone marrow involvement) which was curatively treated with no evidence of disease for ≥5 years. Diagnosis date and treatment confirmation required to be sent to BrUOG. Certification from treating physician that patient is disease free is required. * Resting ECG with QTc \> 470 msec on 2 time-points within a 24 hour period or known family history of long QT syndrome * Patients receiving any systemic chemotherapy or radiotherapy within 3 weeks prior to study treatment * Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks. * Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents. * Concomitant use of the substrates of CYP3A4, CYP1A2, 2B6, 2C9, 2C19 and P-gp should be cautioned while on study. CYP3A4 - hormonal contraceptive, simvastatin, cisapride, cyclosporine, ergot alkaloids, fentanyl, pimozide, sirolimus, tacrolimus and quetiapine CYP1A2 - duloxetine, melatonin CYP2B6 - bupropion, efavirenz CYP2C9 - warfarin CYP2C19 - lansoprazole, omeprazole, S-mephenytoin P-gp - simvastatin, pravastatin, digoxin, dabigatran, colchicine OATP1B1 - bosentan, glibenclamide, repaglinide, statins and valsartan OCT1, MATE1, MATE2K - metformin OCT2 - serum creatinine OAT3 -furosemide, methotrexate * Persistent toxicities deemed related to previous cancer therapy, excluding alopecia. * Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML. * Patients with brain metastases. * Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any prior major surgery. * Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent. * Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication. * Immunocompromised patients that according to treating investigator would increase their risk to protocol treatment, or Patients who are known to be serologically positive for human immunodeficiency virus (HIV). * Patients with a known hypersensitivity to olaparib or any of the excipients of the product. * Patients with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids * Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT) * Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable as long as not within 28 days from study registration). * Major medical or psychiatric illness which, in the investigator's opinion, would prevent completion of treatment and would interfere with follow-up.