Clinical trial NCT01821404: Atorvastatin Before Prostatectomy and Prostate Cancer
Official title: The Impact of Atorvastatin on Prostate Cancer - a Randomized, Pre-surgical Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostatic Neoplasms
Keywords: Apoptosis
Atorvastatin
Inflammation
Pre-surgical trial
Proliferation
Prostate cancer
Lead sponsor: Tampere University Hospital
Sponsor class: OTHER
Collaborators: name: Tampere University
name: Fimlab laboratories
name: University of Eastern Finland
name: Finnish Cultural Foundation
First posted: 2013-04-01
Enrollment: 160
Sex: MALE
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Apoptosis
timeFrame: Four weeks after recruitment
measure: Ki-67 expression
timeFrame: Four weeks after recruitment
measure: Histological inflammation
timeFrame: After prostatectomy
measure: serum PSA
timeFrame: At recruitment and before prostatectomy
Secondary outcomes:
measure: serum cholesterol
timeFrame: At recruitment and again four weeks after
measure: Atorvastatin level in prostate tissue
timeFrame: Four weeks after recruitment
Other outcomes:
measure: Genotype of cholesterol-metabolizing enzymes
timeFrame: Post-hoc analysis, one year after recruitment completes
measure: Genotype of statin-metabolizing enzymes
timeFrame: Post hoc analysis, one year after recruitment completes
measure: Erection function
timeFrame: One year after prostatectomy
Locations:
city: Lahti
country: Finland
facility: Päijät-Häme Central Hospital
city: Pori
country: Finland
facility: Satakunta Central Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital, Department of Urology
Study officials:
affiliation: Tampere University
name: Teemu J Murtola, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Tampere University
name: Teuvo LJ Tammela, M.D., Ph.D.
role: STUDY_DIRECTOR
References:
citation: Raittinen PVH, Syvala H, Tammela TLJ, Hakkinen MR, Ilmonen P, Auriola S, Murtola TJ. Atorvastatin induces adrenal androgen downshift in men with prostate cancer: A post Hoc analysis of a pilot adaptive Randomised clinical trial. EBioMedicine. 2021 Jun;68:103432. doi: 10.1016/j.ebiom.2021.103432. Epub 2021 Jun 16.