TY - JOUR

T1 - Randomised double-blind phase 3 clinical study testing impact of atorvastatin on prostate cancer progression after initiation of androgen deprivation therapy

T2 - study protocol

AU - Siltari, Aino

AU - Riikonen, Jarno

AU - Koskimäki, Juha

AU - Pakarainen, Tomi

AU - Ettala, Otto

AU - Boström, Peter

AU - Seikkula, Heikki

AU - Kotsar, Andres

AU - Tammela, Teuvo

AU - Helminen, Mika

AU - Raittinen, Paavo V.

AU - Lehtimäki, Terho

AU - Fode, Mikkel

AU - Østergren, Peter

AU - Borre, Michael

AU - Rannikko, Antti

AU - Marttila, Timo

AU - Salonen, Arto

AU - Ronkainen, Hanna

AU - Löffeler, Sven

AU - Murtola, Teemu J.

N1 - Publisher Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

PY - 2022

Y1 - 2022

N2 - INTRODUCTION: Blood cholesterol is likely a risk factor for prostate cancer prognosis and use of statins is associated with lowered risk of prostate cancer recurrence and progression. Furthermore, use of statins has been associated with prolonged time before development of castration resistance (CR) during androgen deprivation therapy (ADT) for prostate cancer. However, the efficacy of statins on delaying castration-resistance has not been tested in a randomised placebo-controlled setting.This study aims to test statins' efficacy compared to placebo in delaying development of CR during ADT treatment for primary metastatic or recurrent prostate cancer. Secondary aim is to explore effect of statin intervention on prostate cancer mortality and lipid metabolism during ADT. METHODS AND ANALYSIS: In this randomised placebo-controlled trial, a total of 400 men with de novo metastatic prostate cancer or recurrent disease after primary treatment and starting ADT will be recruited and randomised 1:1 to use daily 80 mg of atorvastatin or placebo. All researchers, study nurses and patients will be blinded throughout the trial. Patients are followed until disease recurrence or death. Primary outcome is time to formation of CR after initiation of ADT. Serum lipid levels (total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and trigyserides) are analysed to test whether changes in serum cholesterol parameters during ADT predict length of treatment response. Furthermore, the trial will compare quality of life, cardiovascular morbidity, changes in blood glucose and circulating cell-free DNA, and urine lipidome during trial. ETHICS AND DISSEMINATION: This study is approved by the Regional ethics committees of the Pirkanmaa Hospital District, Science centre, Tampere, Finland (R18065M) and Tarto University Hospital, Tarto, Estonia (319/T-6). All participants read and sign informed consent form before study entry. After publication of results for the primary endpoints, anonymised summary metadata and statistical code will be made openly available. The data will not include any information that could make it possible to identify a given participant. TRIAL REGISTRATION NUMBER: Clinicaltrial.gov: NCT04026230, Eudra-CT: 2016-004774-17, protocol code: ESTO2, protocol date 10 September 2020 and version 6.

AB - INTRODUCTION: Blood cholesterol is likely a risk factor for prostate cancer prognosis and use of statins is associated with lowered risk of prostate cancer recurrence and progression. Furthermore, use of statins has been associated with prolonged time before development of castration resistance (CR) during androgen deprivation therapy (ADT) for prostate cancer. However, the efficacy of statins on delaying castration-resistance has not been tested in a randomised placebo-controlled setting.This study aims to test statins' efficacy compared to placebo in delaying development of CR during ADT treatment for primary metastatic or recurrent prostate cancer. Secondary aim is to explore effect of statin intervention on prostate cancer mortality and lipid metabolism during ADT. METHODS AND ANALYSIS: In this randomised placebo-controlled trial, a total of 400 men with de novo metastatic prostate cancer or recurrent disease after primary treatment and starting ADT will be recruited and randomised 1:1 to use daily 80 mg of atorvastatin or placebo. All researchers, study nurses and patients will be blinded throughout the trial. Patients are followed until disease recurrence or death. Primary outcome is time to formation of CR after initiation of ADT. Serum lipid levels (total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and trigyserides) are analysed to test whether changes in serum cholesterol parameters during ADT predict length of treatment response. Furthermore, the trial will compare quality of life, cardiovascular morbidity, changes in blood glucose and circulating cell-free DNA, and urine lipidome during trial. ETHICS AND DISSEMINATION: This study is approved by the Regional ethics committees of the Pirkanmaa Hospital District, Science centre, Tampere, Finland (R18065M) and Tarto University Hospital, Tarto, Estonia (319/T-6). All participants read and sign informed consent form before study entry. After publication of results for the primary endpoints, anonymised summary metadata and statistical code will be made openly available. The data will not include any information that could make it possible to identify a given participant. TRIAL REGISTRATION NUMBER: Clinicaltrial.gov: NCT04026230, Eudra-CT: 2016-004774-17, protocol code: ESTO2, protocol date 10 September 2020 and version 6.

KW - clinical trials

KW - prostate disease

KW - urological tumours

U2 - 10.1136/bmjopen-2021-050264

DO - 10.1136/bmjopen-2021-050264

M3 - Journal article

C2 - 35487730

AN - SCOPUS:85129166234

VL - 12

JO - BMJ Open

JF - BMJ Open

SN - 2044-6055

IS - 4

M1 - e050264

ER -