Atorvastatin Before Prostatectomy and Prostate Cancer

Prostatic Neoplasms Clinical Trial

— ESTO1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01821404
• Other study ID #: 2011-005438-20
• Status: Completed
• Phase: Phase 2
• Start date: August 2012
• Est. completion date: May 2017

Study information

• Verified date: May 2018
• Source: Tampere University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: May 2017
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Prostatic Neoplasms

Intervention

Drug:
• Atorvastatin
Capsules including 80 mg of atorvastatin
• Placebo
Similar capsules as in the atorvastatin arm, but without the active ingredient

Locations

Country	Name	City	State
Finland	Päijät-Häme Central Hospital	Lahti
Finland	Satakunta Central Hospital	Pori
Finland	Tampere University Hospital, Department of Urology	Tampere

Sponsors (5)

Lead Sponsor	Collaborator
Tampere University Hospital	Fimlab laboratories, Finnish Cultural Foundation, University of Eastern Finland, University of Tampere

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Genotype of cholesterol-metabolizing enzymes	Genotyping of cholesterol-metabolizing enzymes from blood and tissue samples	Post-hoc analysis, one year after recruitment completes
Other	Genotype of statin-metabolizing enzymes	Genotyping statin-metabolizing enzymes from blood and tissue samples	Post hoc analysis, one year after recruitment completes
Other	Erection function	Erectile function as measured with IIEF-5 questionnaire before prostatectomy and again at 3 month intervals during the first year after prostatectomy	One year after prostatectomy
Primary	Apoptosis	Number of apoptotic cells in prostate tissue. Measured after radical prostatectomy, on average after 4 weeks of recruitment	Four weeks after recruitment
Primary	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
Primary	Histological inflammation	Extent of histological inflammation in the prostate tissue as evaluated by study pathologist	After prostatectomy
Primary	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	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
Secondary	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