Impact of Atorvastatin on Prostate Cancer Progression During ADT (ESTO2)

October 19, 2022 updated by: Teemu Murtola, Tampere University Hospital

Impact of Atorvastatin on Prostate Cancer Progression After Initiation of Androgen Deprivation Therapy - Lipid Metabolism as a Novel Biomarker to Predict Prostate Cancer Progression

This randomized double-blind placebo-controlled trial tests whether intervention with atorvastatin delays development of castration resistance compared to placebo during androgen deprivation therapy (ADT) for prostate cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Cholesterol-lowering statin drugs have been reported to lower proliferation activity in prostate cancer, delay occurrence of castration resistance and reduce the risk of prostate cancer death. Therefore, it is important to test statins' efficacy in addition to conventional prostate cancer treatment in a randomized, placebo-controlled trial.

This phase 3 randomized double-blind placebo-controlled trial will explore whether intervention with atorvastatin delays prostate cancer progression i.e. development of castration resistance compared to placebo during androgen deprivation therapy (ADT) for metastatic or recurrent prostate cancer.

Secondary objectives include exploring whether atorvastatin lowers prostate cancer-specific or overall mortality compared to placebo, and to demonstrate whether changes in serum lipid parameters predict disease recurrence and occurrence of adverse genomic changes predicting castration resistance among prostate cancer patients during ADT.

The study recruitment target is 400 participants who start ADT as management of metastatic or recurrent prostate cancer. These men will be randomized 1:1 (200 + 200) to receive blinded study drug, either 80 mg of atorvastatin daily or placebo until disease recurrence i.e. development of castration resistance or for a maximum of five years.

The study will be carried out in collaboration between urological departments of University Hospitals in Finland as a project of the national FinnProstata study group, Herlev University Hospital in Denmark, Vestfold and Telemark hospitals in Norway and the Tartu University Hospital in Estonia.

Follow-up is continued until the primary end-point, development of castration resistance. After this the participants will be given the opportunity to voluntarily carry on with the blinded intervention for maximum time of ten year to observe effects on survival after development of castration resistance. Blinding will be lifted after the follow-up is complete for all study participants.

Castration resistance is defined as prostate-specific antigen (PSA) progression (three consecutive rises of PSA measured at least 1 week apart with two > 50% increases over the nadir and PSA > 2 ng/ml) or radiological disease progression (appearance of two or more lesions in bone scan or soft tissue enlargement as per RECIST criteria) with serum testosterone at castrate level (< 1.73 nmol/l; 50 ng/dl) during ADT.

Study Type

Interventional

Enrollment (Anticipated)

400

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Denmark
  • Estonia
      • Tartu, Estonia
  • Finland
      • Helsinki, Finland
        • Recruiting
        • Helsinki University Hospital, Department of Urology
        • Contact:
      • Jyväskylä, Finland
      • Kuopio, Finland
        • Not yet recruiting
        • Kuopio University Hospital, Department of Urology
        • Contact:
      • Seinäjoki, Finland
        • Recruiting
        • Seinäjoki Central Hospital, Department of Surgery
        • Contact:
      • Tampere, Finland
      • Turku, Finland
        • Recruiting
        • Turku University Hospital
        • Contact:
  • Norway
      • Skien, Norway
      • Tønsberg, Norway

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Histopathologically confirmed metastatic (radiologically confirmed bone or soft tissue metastasis or enlarged lymph nodes at minimum 15 mm in diameter beyond the pelvic lymph nodes) or recurrent (requiring treatment after curative-intent surgery or radiotherapy) adenocarcinoma of the prostate for which androgen deprivation or antiandrogen therapy (GnRH agonist/antagonist, bicalutamide/flutamide, surgical castration or enzalutamide/abiraterone monotherapy) is initiated as definitive treatment no longer than 3 months before recruitment

    • previous prostatectomy and radiation therapy allowed
    • ADT/antiandrogen therapy for neoadjuvant hormone therapy is not included
  • Willingness to participate and signing of informed consent

Exclusion Criteria:

  • Statin use at the time of recruitment or within 6 months of it
  • Previous adverse effects during statin therapy
  • Familial hypercholesterolemia or very high total cholesterol (9.3 mmol/l or above)
  • Clinically significant renal insufficiency (serum creatinine above 170 µmol/l) or liver insufficiency (serum alanine aminotransferase more than 2x above the upper limit of normal range)
  • Use of drugs that may interact with statins (St John's Wort, HIV protease inhibitors, ciclosporin, macrolide antibiotics, fucidic acid, phenytoin, carbamazepine, dronedarone or oral antifungal medication).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Atorvastatin
Capsules of atorvastatin. Daily dose of 80 mg for max. 10 years or until development of castration resistance.
Drug: Atorvastatin 80mg
Capsules including 80 mg of atorvastatin
Other Names:
  • Lipitor
Placebo Comparator: Placebo
Identical capsules as in the atorvastatin arm, but including no active ingredient. Used daily for max. 10 years or until development of castration resistance
Drug: Placebo oral capsule
Similar capsules as in the atorvastatin arm, but without the active ingredient

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Castration resistance
Time Frame: From date of randomization until the date of first occurrence of castration resistance, assessed up to 60 months
Castration resistance is defined as PSA progression (three consecutive PSA rises measured at least 1 week apart with two > 50% increases over the nadir and PSA > 2 ng/ml) or radiological disease progression (appearance of two or more lesions in bone scan or soft tissue enlargement as per RECIST criteria) with serum testosterone at castrate level (< 1.73 nmol/l; 50 ng/dl) during ADT.
From date of randomization until the date of first occurrence of castration resistance, assessed up to 60 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Lipid levels
Time Frame: From date of randomization until the date of first occurrence of castration resistance or death, whichever came first, assessed at 6 month intervals up to 60 months
Change in serum lipid levels during the intervention. Measured at baseline and in every follow-up visit. Results are blinded from the investigators and participants before the final analysis
From date of randomization until the date of first occurrence of castration resistance or death, whichever came first, assessed at 6 month intervals up to 60 months
Prostate cancer mortality
Time Frame: From date of randomization until the date of prostate cancer death, assessed up to 60 months
Followed through Finnish national registries after reaching the primary end-point
From date of randomization until the date of prostate cancer death, assessed up to 60 months
Overall survival
Time Frame: From date of randomization until the date of death due to any cause, assessed up to 60 months
Followed through Finnish national registries after reaching the primary end-point
From date of randomization until the date of death due to any cause, assessed up to 60 months
Circulating cell-free DNA
Time Frame: At enrollment and at occurrence of castration resistance, assessed up to 60 months
Occurrence of adverse tumor traits predicting development of castration resistance in circulating cell free DNA
At enrollment and at occurrence of castration resistance, assessed up to 60 months
Fasting blood glucose
Time Frame: From date of randomization until the date of first occurrence of castration resistance or death, whichever came first, assessed at 6 month intervals up to 60 months
To see how ADT affects glucose tolerance and whether atorvastatin intervention has any effect on it
From date of randomization until the date of first occurrence of castration resistance or death, whichever came first, assessed at 6 month intervals up to 60 months
Occurrence of cardiovascular events during ADT
Time Frame: From date of randomization until the date of first occurrence of castration resistance or death, whichever came first, assessed at 6 month intervals up to 60 months
Any cardiovascular events as described by the participant or evident from the patient files during the course of follow-up. Followed via national registries after meeting the primary end-point.
From date of randomization until the date of first occurrence of castration resistance or death, whichever came first, assessed at 6 month intervals up to 60 months
General quality of life (QOL)
Time Frame: From date of randomization until the date of first occurrence of castration resistance or death, whichever came first, assessed at 12 month intervals up to 60 months
Score from validated QOL questionnaire EORTC QLQ-C30 (range 0-100, with 100 denoting highest quality of life)
From date of randomization until the date of first occurrence of castration resistance or death, whichever came first, assessed at 12 month intervals up to 60 months
Prostate cancer-specific quality of life (QOL)
Time Frame: From date of randomization until the date of first occurrence of castration resistance or death, whichever came first, assessed at 12 month intervals up to 60 months
Score from validated QOL questionnaire EORTC QLQ-PR25 (range 0-100, with 100 denoting highest quality of life)
From date of randomization until the date of first occurrence of castration resistance or death, whichever came first, assessed at 12 month intervals up to 60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tampere University Hospital

Collaborators

Turku University Hospital
Helsinki University Central Hospital
Oulu University Hospital
Kuopio University Hospital
University of Aarhus
The Hospital of Vestfold
Seinajoki Central Hospital
Central Finland Hospital District
Tartu University Hospital
Fimlab laboratories
Telemark Hospital Trust

Investigators

  • Principal Investigator: Teemu Murtola, MD, PhD, Tampere University Hospital
  • Study Director: Otto Ettala, MD, PhD, Turku University Hospital
  • Study Director: Heikki Seikkula, Central Finland Central Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 15, 2019

Primary Completion (Anticipated)

December 31, 2025

Study Completion (Anticipated)

December 31, 2025

Study Registration Dates

First Submitted

June 25, 2018

First Submitted That Met QC Criteria

July 17, 2019

First Posted (Actual)

July 19, 2019

Study Record Updates

Last Update Posted (Actual)

October 21, 2022

Last Update Submitted That Met QC Criteria

October 19, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016-004774-17

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Sharing of individual-level data is not allowed by ethics board

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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