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

Study Overview
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Brief Summary
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This is a 2x2 factorial randomized, multicenter, international, open phase III trial. The primary objective is to evaluate the benefit of acetylsalicylic acid and atorvastatin on overall survival (OS) (main endpoint) for patients with castrate-resistant prostate cancer starting first line treatment for CRPC

Official Title
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A Phase III Trial of Acetylsalicylic Acid and Atorvastatin in Patients With Castrate-resistant Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Acetylsalicylic acid
* Drug: Atorvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed adenocarcinoma of the prostate and no curative local therapy considered possible Age ≥ 18 years, life expectancy of at least 6 months CRPC defined as tumor progression (PSA increase on at least 2 separate values separated by at least 1 week or progression on imaging) while on Androgen Deprivation Therapy (orchiectomy, LHRH agonist or -antagonist) with documented serum testosterone levels ≤ 1.7 nmol/L (≤ 0.50 ng/mL). Ongoing concurrent use of LHRH agonist 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 of these agents together with Androgen Deprivation Therapy (ADT) for castrate-sensitive disease is allowed. Adequate renal function within 30 days prior to registration: calculated creatinine clearance ≥ 50 mL/min, according to the formula of Cockcroft-Gault and adequate liver 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 same primary 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 localized non-melanoma skin cancer and Ta or Tis bladder cancer (patients with asymptomatic Chronic Lymphocytic Leukemia can be included) Previous metastatic malignancy within 5 years Patient currently taking daily acetylsalicylic acid or a daily statin within the last 6 months Patients with active liver disease (hepatitis B or C, cirrhosis) or unexplained persistent elevations of serum transaminases exceeding 3 times the upper limit of normal or cholestasis Patients with excessive alcohol intake or history of a relevant liver disease Known hypersensitivity or intolerance to acetylsalicylic acid or atorvastatin or hypersensitivity 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 the product information (e.g. Fusidic acid, potent inhibitors of CYP3A4 or transport proteins: ciclosporin, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole and HIV protease inhibitors including ritonavir, lopinavir, atazanavir, indinavir, darunavir, tipranavir, telaprevir, saquinavir, darunavir, fosamprenavir, boceprevir, gemfibrozil, fenofibrate, etc) Any serious underlying medical condition (by the investigator's judgement) which could impair the ability of the patient to participate in the trial Patients with hereditary galactose intolerance, Lapp-lactase deficiency or Glucose-Galactose-malabsorption Compliance with trial medical follow-up impossible due to geographic, social or psychological reasons Psychiatric disorder precluding understanding of information about trial related topics, providing informed consent, or interfering with compliance for oral drug intake

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: This is a 2x2 factorial randomized, multicenter, international, open phase III trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Arm A<br>Standard of Care (SOC) for CRPC | |
| Experimental: Arm B<br>SOC + acetylsalicylic acid 100 mg daily | Drug: Acetylsalicylic acid<br>* 100mg<br>|
| Experimental: Arm C<br>SOC + atorvastatin 80 mg daily | Drug: Atorvastatin<br>* 80 mg<br>|
| Experimental: Arm D<br>SOC + acetylsalicylic acid 100 mg daily + atorvastatin 8 | Drug: Acetylsalicylic acid<br>* 100mg<br>Drug: Atorvastatin<br>* 80 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) |  | OS will be calculated from the date of randomization to the date of death up to 15 years |