Impact of Atorvastatin on Prostate Cancer Progression During ADT

NCT04026230 | Unknown Phase 3 DMC

• 1 other identifier: 2016-004774-17
• Study Type: interventional
• Target: 400
• Locations: 4 countries
• Sites: 10

Brief Summary

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.

Conditions

Metastatic Prostate Cancer; Recurrent Prostate Cancer

Keywords

Prostate cancer; Castration resistance; Cholesterol lowering drug; Cholesterol; Atorvastatin; Survival; Mortality

Outcome Measures

Primary Outcomes (1)

• Castration resistance

  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 Outcomes (8)

• Lipid levels

  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

  From date of randomization until the date of prostate cancer death, assessed up to 60 months

• Overall survival

  From date of randomization until the date of death due to any cause, assessed up to 60 months

• Circulating cell-free DNA

  At enrollment and at occurrence of castration resistance, assessed up to 60 months

• Fasting blood glucose

  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

Study Arms (2)

Atorvastatin

EXPERIMENTAL

Capsules of atorvastatin. Daily dose of 80 mg for max. 10 years or until development of castration resistance.

Drug: Atorvastatin 80mg

Placebo

PLACEBO COMPARATOR

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

Interventions

Atorvastatin 80mg DRUG

Capsules including 80 mg of atorvastatin

Also known as: Lipitor

Atorvastatin

Placebo oral capsule DRUG

Similar capsules as in the atorvastatin arm, but without the active ingredient

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Tampere University Hospital: lead
• Turku University Hospital: collaborator
• Central Finland Hospital District: collaborator
• Tartu University Hospital: collaborator
• University of Aarhus: collaborator
• Fimlab laboratories: collaborator
• Helsinki University Central Hospital: collaborator
• Kuopio University Hospital: collaborator
• Oulu University Hospital: collaborator
• Seinajoki Central Hospital: collaborator
• The Hospital of Vestfold: collaborator
• Telemark Hospital Trust: collaborator

Study Sites (10)

Herlev and Gentofte Hospital

Herlev, Denmark

NOT YET RECRUITING

Tartu University Hospital

Tartu, Estonia

RECRUITING

Helsinki University Hospital, Department of Urology

Helsinki, Finland

RECRUITING

Central Finland central hospital

Jyväskylä, Finland

RECRUITING

Kuopio University Hospital, Department of Urology

Kuopio, Finland

NOT YET RECRUITING

Seinäjoki Central Hospital, Department of Surgery

Seinäjoki, Finland

RECRUITING

Tampere University Hospital

Tampere, Finland

RECRUITING

Turku University Hospital

Turku, Finland

RECRUITING

The Hospital of Telemark

Skien, Norway

RECRUITING

The Hospital of Vestfold

Tønsberg, Norway

RECRUITING

Related Publications (1)

• Siltari A, Riikonen J, Koskimaki J, Pakarainen T, Ettala O, Bostrom P, Seikkula H, Kotsar A, Tammela T, Helminen M, Raittinen PV, Lehtimaki T, Fode M, Ostergren P, Borre M, Rannikko A, Marttila T, Salonen A, Ronkainen H, Loffeler S, Murtola TJ. Randomised double-blind phase 3 clinical study testing impact of atorvastatin on prostate cancer progression after initiation of androgen deprivation therapy: study protocol. BMJ Open. 2022 Apr 29;12(4):e050264. doi: 10.1136/bmjopen-2021-050264.

  PMID: 35487730 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Teemu Murtola, MD, PhD

  Tampere University Hospital

  PRINCIPAL INVESTIGATOR

• Otto Ettala, MD, PhD

  Turku University Hospital

  STUDY DIRECTOR

• Heikki Seikkula

  Central Finland Central Hospital

  STUDY DIRECTOR

Central Study Contacts

Teemu Murtola, MD, PhD

CONTACT

+358-3 311 65015; teemu.murtola@uta.fi

Aino Siltari, PhD

CONTACT

aino.siltari@helsinki.fi

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, professor

Study Record Dates

• First Submitted: June 25, 2018
• First Posted: July 19, 2019
• Study Start: August 15, 2019
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: October 21, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); FI (6); DK (1); NO (2)