CaNCaP03

1. Have given written informed consent to participate
2. Men aged 18 years or over
3. Patients suitable for radical prostatectomy
4. ECOG performance status of 0 or 1
5. Access to archived diagnostic tissue or consent to undergo repeat biopsy, if necessary

6. Diagnosis of High risk or Intermediate risk prostate cancer, defined as:

   1. High-risk disease: one or more of stage T2c - 3a, or PSA level >20ng/mL, or Gleason score ≥ 8
   2. Intermediate risk disease: two or more of Stage T2 (any), PSA > 10, Gleason of ≥ 7

7. Adequate bone marrow reserve and organ function (measured within 28 days prior to planned first olaparib administration) as demonstrated by the following values:

   1. Absolute neutrophil count ≥ 1.8 x 109/L
   2. Haemoglobin ≥ 117g/L
   3. Platelet count ≥ 135 x 109/L
   4. WBC ≥ 3.6 x 109/L
   5. Peripheral blood smear with no features of MDS/AML
   6. Adequate hepatic function:
      1. Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 1.5 times the upper limit of normal (ULN) AND
      2. Total bilirubin ≤ 1.5 times the ULN unless in the presence of Gilbert's syndrome with an elevated indirect fraction
   7. Adequate renal function:
      1. Serum creatinine ≤ 1.5 times the ULN concurrent with creatinine clearance ≥ 50mL/min (calculated by Cockcroft and Gault equation)

   8. Willing to use two highly effective forms of contraception (see section 11.8) throughout their participation in the trial and for three months after their last dose of olaparib. Patients must refrain from donating sperm from the start of dosing up until sixteen weeks after discontinuing trial treatment

   9. Normal chest radiograph (CXR) and oxygen saturations
   10. Patients who are currently/have recently been involved in non-drug-based research are eligible to participate

*If the patient does not consent to participate in the optional genetic research (ctDNA studies on blood) or to optional additional biopsies there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the trial.

The presence of any of the following will preclude patient inclusion:

1. Contraindication to olaparib or degarelix
2. History of hypersensitivity to active or inactive excipients of olaparib
3. Patients with known hypersensitivity to the degarelix active substance or mannitol must not receive degarelix.
4. Current refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of olaparib

5. As judged by the Investigator, any patient considered a poor medical risk due to a serious uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection including but not limited to:

   1. Uncontrolled ventricular arrhythmia
   2. Recent myocardial infarction (within three months)
   3. Unstable spinal cord compression
   4. Superior vena cava syndrome
   5. Extensive bilateral lung disease on High Resolution Computed Tomography (HRCT)
   6. History of pneumonitis
   7. Active infection including hepatitis B, hepatitis C and Human Immunodeficiency Virus. Screening for chronic conditions is not required.
6. Major surgery within 4 weeks prior to entry into the trial (excluding placement of vascular access). Patients must have recovered from side effects of any major surgery. Minor surgery (not including the diagnostic prostate biopsy) within 2 weeks prior to entry into the trial.
7. Patients who have received (within last 3 months of trial entry) an investigational drug within a clinical trial will not be eligible to participate.
8. Concomitant use of known potent CYP3A4 inhibitors and inducers. See section 10.4.1.1 for list and consider wash out periods.
9. Blood transfusions within 1 month prior to the trial start
10. ECG with mean resting QTc of ≥ 470ms (Fridericia; as per local reading) on two or more time points within a 24 hour period or family history of long QT syndrome
11. Concomitant medications known to prolong the QT interval (see Appendix 1) or with factors that increase the risk of QTc prolongation or risk of arrhythmic events (such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age), History of Torsades de pointes.
12. Judgement by the Investigator that the patient is unsuitable to participate in the trial and the patient is unlikely to comply with trial procedures, restrictions and requirements
13. Patients with MDS or AML, or other previous malignancy except patients that have undergone treatment with curative intent for prior malignancy with no evidence of active prior malignancy are eligible.
14. With the exception of alopecia, any unresolved toxicities from prior chemotherapy should be no greater than CTCAE (version 4.03) Grade 1 at the time of starting olaparib treatment.
15. Patients with a desire to have children following the trial will not be recruited