Atorvastatin Before Prostatectomy and Prostate Cancer

Study Overview
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Brief Summary
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This single-center, randomized, double-blind trial assesses the impact of short-term atorvastatin administration on proliferation activity, apoptotic rate and histological inflammation in prostate tissue.

Detailed Description
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In this trial 160 men who have been diagnosed with prostate cancer, and whose first-line treatment will be radical prostatectomy (surgical removal of the prostate), are randomized to receive either 80 mg atorvastatin or placebo daily for 2-5 weeks until the operation. Blood cholesterol and serum PSA are measured before starting the study drug use and before the operation. After the operation change in PSA and histological inflammation, apoptotic rate and Ki-67 staining intensity are compared between atorvastatin-treated and placebo-treated men. The correlation between changes in serum cholesterol or prostate specific antigen (PSA) and the tissue characteristics is evaluated. After recruiting 60 men we will perform an interim analysis on primary end-points without breaking the blinding to treatment allocation. If we observe a statistically significant difference in all primary end-points, the trial will be stopped early and the results published. Additionally, atorvastatin concentration in the blood and the prostate tissue is measured with mass spectrometry to determine penetrance of atorvastatin into the prostate. DNA- and RNA-samples are obtained from the prostate tissue and the blood. These will be used to study how gene expression of statin- and cholesterol-modifying enzymes affects the responses observed in prostate tissue. As a secondary end-point we will measure recovery of erectile function after the operation and compare between the two study arms. Erectile function is measured using IIEF-5 questionnaire once before the operation and again 3, 6, 9 and 12 months from the prostatectomy.

Official Title
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The Impact of Atorvastatin on Prostate Cancer - a Randomized, Pre-surgical Clinical Trial

Conditions
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Prostatic Neoplasms

Intervention / Treatment
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* Drug: Atorvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prostate cancer proven histologically in prostate biopsy Radical prostatectomy selected as the first-line treatment Willingness to participate and sign informed consent Exclusion Criteria: Previous oncological treatments for any malignancy Previous usage of statins, finasteride or dutasteride within a year prior to prostate cancer diagnosis Clinically significant liver- or kidney insufficiency (plasma alanine aminotransferase level is twice over the recommended upper limit or serum creatinine level is over 170 µmol/l) Previous adverse effects from cholesterol-lowering treatment Ongoing use of drugs having interactions with statins (St John's Wort, HIV protease inhibitors, ciclosporin, macrolide antibiotics, fusidic acid, phenytoin, carbamazepine, dronedarone or oral antifungal medication)

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Similar capsules as in the atorvastatin arm, but including no active ingredient. Used daily for 3-5 weeks before prostatectomy | Drug: Placebo<br>* Similar capsules as in the atorvastatin arm, but without the active ingredient<br>|
| Experimental: Atorvastatin<br>Atorvastatin capsules orally, 80 mg daily for 3-5 weeks before prostatectomy | Drug: Atorvastatin<br>* Capsules including 80 mg of atorvastatin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apoptosis | Number of apoptotic cells in prostate tissue. Measured after radical prostatectomy, on average after 4 weeks of recruitment | Four weeks after recruitment | 
| Ki-67 expression | Cellular proliferation activity in prostate tissue as measured by Ki-67 expression. Measured after radical prostatectomy, on average after 4 weeks of recruitment | Four weeks after recruitment | 
| Histological inflammation | Extent of histological inflammation in the prostate tissue as evaluated by study pathologist | After prostatectomy | 
| serum PSA | Change in serum PSA level as measured before starting the study drug and again just before prostatectomy | At recruitment and before prostatectomy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum cholesterol | Changes in measured fasting serum cholesterol parameters: total cholesterol, HDL and LDL. First measure is done at recruitment, another right before radical prostatectomy. | At recruitment and again four weeks after | 
| Atorvastatin level in prostate tissue | Measurement of atorvastatin level in prostate tissue with mass spectrometry. Measured after radical prostatectomy, on average four weeks after recruitment | Four weeks after recruitment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atorvastatin, Inflammation, Pre-surgical trial, Proliferation, Prostate cancer, Apoptosis