Trial of Acetylsalicylic Acid and Atorvastatin in Patients With Castrate-resistant Prostate Cancer

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate and no curative localtherapy considered possible

• Age ≥ 18 years, life expectancy of at least 6 months

• CRPC defined as tumor progression (PSA increase on at least 2 separate valuesseparated by at least 1 week or progression on imaging) while on AndrogenDeprivation Therapy (orchiectomy, LHRH agonist or -antagonist) with documented serumtestosterone levels ≤ 1.7 nmol/L (≤ 0.50 ng/mL). Ongoing concurrent use of LHRHagonist or antagonist is required if the patient has not been surgically castrated

• Presence (M1) or absence (M0) of metastases on imaging

• Performance status 0, 1 or 2

• No previous use of life- prolonging treatments for CRPC (including abiraterone,enzalutamide, radium-223, docetaxel, cabazitaxel, and sipuleucel-T). The use ofthese agents together with Androgen Deprivation Therapy (ADT) for castrate-sensitivedisease is allowed.

• Adequate renal function within 30 days prior to registration: calculated creatinineclearance ≥ 50 mL/min, according to the formula of Cockcroft-Gault and adequateliver function with levels of AST and ALT ≤ 3xULN and no signs for cholestasis.

• Participation in other clinical trials is allowed except for trials with the sameprimary endpoint, i.e. OS

• Patient authorized to participate to a clinical trial by specific country regulation (eg patient affiliated to a social security system or beneficiary of the same)

• Information delivered to patient and informed consent form signed by the patient.

Exclusion Criteria:

• Previous localised malignancy within 2 years with the exception of localizednon-melanoma skin cancer and Ta or Tis bladder cancer (patients with asymptomaticChronic Lymphocytic Leukemia can be included)

• Previous metastatic malignancy within 5 years

• Patient currently taking daily acetylsalicylic acid or a daily statin within thelast 6 months

• Patients with active liver disease (hepatitis B or C, cirrhosis) or unexplainedpersistent elevations of serum transaminases exceeding 3 times the upper limit ofnormal or cholestasis

• Patients with excessive alcohol intake or history of a relevant liver disease

• Known hypersensitivity or intolerance to acetylsalicylic acid or atorvastatin orhypersensitivity to any of its components

• Contra-indication to acetylsalicylic acid or atorvastatin according to label,including known high-risk for haemorrhage,

• History of or active myopathy or significantly elevated (> 5 times ULN) CK levels

• History of recent stroke or transient ischemic attack (TIA).

• Any concomitant drugs contraindicated for use with the trial drugs according to theproduct information (e.g. Fusidic acid, potent inhibitors of CYP3A4 or transportproteins: ciclosporin, telithromycin, clarithromycin, delavirdine, stiripentol,ketoconazole, voriconazole, itraconazole, posaconazole and HIV protease inhibitorsincluding ritonavir, lopinavir, atazanavir, indinavir, darunavir, tipranavir,telaprevir, saquinavir, darunavir, fosamprenavir, boceprevir, gemfibrozil,fenofibrate, etc)

• Any serious underlying medical condition (by the investigator's judgement) whichcould impair the ability of the patient to participate in the trial

• Patients with hereditary galactose intolerance, Lapp-lactase deficiency orGlucose-Galactose-malabsorption

• Compliance with trial medical follow-up impossible due to geographic, social orpsychological reasons

• Psychiatric disorder precluding understanding of information about trial relatedtopics, providing informed consent, or interfering with compliance for oral drugintake