Prostatic NeoplasmsPhase 2ESTO1NCT01821404
Atorvastatin Before Prostatectomy and Prostate Cancer
A Phase 2 study testing Atorvastatin in people with Prostatic Neoplasms, run by Tampere University Hospital at 3 sites in Finland.
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. Read more about this study
- Who is it for?
- Ages 40 to 80 years, men only
- Conditions the study is for
- Prostatic Neoplasms
- What is being tested?
- Atorvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 3 sitesFinland
- Study dates
- Aug 2012to May 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Prostate cancer proven histologically in prostate biopsy
- Radical prostatectomy selected as the first-line treatment
- Willingness to participate and sign informed consent
Who cannot join
- 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)
Trial locations and contacts
3 sites in 1 country.
Finland3 sites
Päijät-Häme Central Hospital
Lahti
Satakunta Central Hospital
Pori
Tampere University Hospital, Department of Urology
Tampere, 33521
About this study
Official title: The Impact of Atorvastatin on Prostate Cancer - a Randomized, Pre-surgical Clinical Trial
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.
Read the 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.
- Conditions
- Prostatic Neoplasms
- Being tested
- Atorvastatin, Placebo
- Keywords
- Apoptosis, Atorvastatin, Inflammation, Pre-surgical trial, Proliferation, Prostate cancer
- Medical subject headings
- Prostatic Neoplasms, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtorvastatinDrug
Capsules including 80 mg of atorvastatin
PlaceboDrug
Similar capsules as in the atorvastatin arm, but without the active ingredient
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Similar capsules as in the atorvastatin arm, but including no active ingredient. Used daily for 3-5 weeks before prostatectomy Receives: Drug: Placebo |
| Atorvastatin | Experimental | Atorvastatin capsules orally, 80 mg daily for 3-5 weeks before prostatectomy Receives: Drug: Atorvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Apoptosis
Number of apoptotic cells in prostate tissue. Measured after radical prostatectomy, on average after 4 weeks of recruitment
Measured: 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
Measured: Four weeks after recruitment
Histological inflammation
Extent of histological inflammation in the prostate tissue as evaluated by study pathologist
Measured: After prostatectomy
serum PSA
Change in serum PSA level as measured before starting the study drug and again just before prostatectomy
Measured: At recruitment and before prostatectomy
Secondary outcomes (2)
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.
Measured: 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
Measured: Four weeks after recruitment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2013 (estimated)
- Study startAug 2012
- Primary completionMay 2017
- Study completionMay 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prostatic NeoplasmsStudies of the same condition, open and under way.
- More trials run by Tampere University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tampere University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Tampere University, Fimlab laboratories, University of Eastern Finland, Finnish Cultural Foundation
- Responsible party
- Principal investigator, Teemu Murtola, Tampere University Hospital
- Investigators
- Teemu J Murtola, M.D., Ph.D., Principal investigator, Tampere UniversityTeuvo LJ Tammela, M.D., Ph.D., Study director, Tampere University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01821404
- Sponsor's protocol ID
- 2011-005438-20
- Acronym
- ESTO1
- Status last verified
- May 2018
- First submitted
- 22 Mar 2013
- Last updated
- 7 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 34144486
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Atorvastatin on Prostate Cancer - a Randomized, Pre-surgical Clinical Trial
- ClinicalTrials.gov ID
- NCT01821404
- Acronym / sponsor ID
- ESTO1 / 2011-005438-20
- Conditions
- Prostatic Neoplasms
- Keywords
- Apoptosis, Atorvastatin, Inflammation, Pre-surgical trial, Proliferation, Prostate cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- Tampere University HospitalUniversity, hospital or other
- Collaborators
- Tampere University, Fimlab laboratories, University of Eastern Finland, Finnish Cultural Foundation
- Study start
- Aug 2012
- Primary completion
- May 2017 (actual)
- Study completion
- May 2017 (actual)
- First posted
- 1 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboSimilar capsules as in the atorvastatin arm, but including no active ingredient. Used daily for 3-5 weeks before prostatectomy |
| Atorvastatin | Experimental | Drug: AtorvastatinAtorvastatin capsules orally, 80 mg daily for 3-5 weeks before prostatectomy |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Prostate cancer proven histologically in prostate biopsy
- Radical prostatectomy selected as the first-line treatment
- Willingness to participate and sign informed consent
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtorvastatinCapsules including 80 mg of atorvastatin | Drug | Atorvastatin |
| PlaceboSimilar capsules as in the atorvastatin arm, but without the active ingredient | Drug | Placebo |
Primary outcome
Apoptosis
Time frame: Four weeks after recruitment
Number of apoptotic cells in prostate tissue. Measured after radical prostatectomy, on average after 4 weeks of recruitment
Ki-67 expression
Time frame: Four weeks after recruitment
Cellular proliferation activity in prostate tissue as measured by Ki-67 expression. Measured after radical prostatectomy, on average after 4 weeks of recruitment
Histological inflammation
Time frame: After prostatectomy
Extent of histological inflammation in the prostate tissue as evaluated by study pathologist
serum PSA
Time frame: At recruitment and before prostatectomy
Change in serum PSA level as measured before starting the study drug and again just before prostatectomy
2 secondary outcomes
serum cholesterol
Time frame: At recruitment and again four weeks after
Atorvastatin level in prostate tissue
Time frame: Four weeks after recruitment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2018.
- Derived from this study: PubMed 34144486Raittinen 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.
Related trials for Prostatic Neoplasms
RecruitingPhase 2
The COSMYC Trial (COmbined Suppression of MYC)
Metastatic Castration-resistant Prostate Cancer
Not yet recruitingPhase 3
A Study of JNJ-101556143 With Best Supportive Care in Participants With Metastatic Prostate Cancer
Prostatic Neoplasms
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingObservational study
PULSE Registry: for Patients Receiving Lutetium (177Lu) Vipivotide Tetraxetan
Metastatic Prostate Cancer
RecruitingPhase 2
Relugolix and Enzalutamide in Combination With Radiation Therapy for the Treatment of Very High Risk Prostate Cancer, OPTIMAL Trial
Prostate Adenocarcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Teemu J Murtola, M.D., Ph.D. principal investigator
Tampere University
Teuvo LJ Tammela, M.D., Ph.D. study director
Tampere University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atorvastatin in people with Prostatic Neoplasms, run by Tampere University Hospital at 3 sites in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Apoptosis (time frame: Four weeks after recruitment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01821404, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2018.