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Trial record 74 of 93 for:    Recruiting, Not yet recruiting, Available Studies | "Cholesterol"

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

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ClinicalTrials.gov Identifier: NCT04026230
Recruitment Status : Recruiting
First Posted : July 19, 2019
Last Update Posted : September 11, 2019
Sponsor:
Collaborators:
Turku University Hospital
Central Finland Hospital District
Tartu University Hospital
University of Aarhus
Fimlab laboratories
Helsinki University Central Hospital
Kuopio University Hospital
Information provided by (Responsible Party):
Teemu Murtola, Tampere University Hospital

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.

Condition or disease Intervention/treatment Phase
Metastatic Prostate Cancer Recurrent Prostate Cancer Drug: Atorvastatin 80mg Drug: Placebo oral capsule Phase 3

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 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 five 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Impact of Atorvastatin on Prostate Cancer Progression After Initiation of Androgen Deprivation Therapy - Lipid Metabolism as a Novel Biomarker to Predict Prostate Cancer Progression
Actual Study Start Date : August 15, 2019
Estimated Primary Completion Date : December 31, 2025
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Atorvastatin
Capsules of atorvastatin. Daily dose of 80 mg for max. 5 years or until development of castration resistance.
Drug: Atorvastatin 80mg
Capsules including 80 mg of atorvastatin
Other Name: Lipitor

Placebo Comparator: Placebo
Identical capsules as in the atorvastatin arm, but including no active ingredient. Used daily for max. 5 years or until development of castration resistance
Drug: Placebo oral capsule
Similar capsules as in the atorvastatin arm, but without the active ingredient




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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)

  8. 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)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04026230


Contacts
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Contact: Teemu Murtola, MD, PhD +358-3 311 65015 teemu.murtola@uta.fi
Contact: Aino Siltari, PhD aino.siltari@helsinki.fi

Locations
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Denmark
Herlev and Gentofte Hospital Not yet recruiting
Herlev, Denmark
Contact: Mikkel Fode, MD, PhD       mikkelfode@gmail.com   
Contact: Peter Oestergren, MD, PhD       peter.busch.oestergren@regionh.dk   
Estonia
Tartu University Hospital Not yet recruiting
Tartu, Estonia
Contact: Andres Kotsar, MD, PhD       andres.kotsar@gmail.com   
Finland
Helsinki University Hospital, Department of Urology Not yet recruiting
Helsinki, Finland
Contact: Antti Rannikko, MD,PhD       antti.rannikko@hus.fi   
Central Finland central hospital Not yet recruiting
Jyväskylä, Finland
Contact: Heikki Seikkula, MD, PhD       heikki.seikkula@ksshp.fi   
Kuopio University Hospital, Department of Urology Not yet recruiting
Kuopio, Finland
Contact: Arto Salonen, MD,PhD       arto.salonen@kuh.fi   
Seinäjoki Central Hospital, Department of Surgery Recruiting
Seinäjoki, Finland
Contact: Teemu Murtola, MD,PhD       teemu.murtola@epshp.fi   
Tampere University Hospital Recruiting
Tampere, Finland
Contact: Teemu Murtola, MD, PhD       teemu.murtola@tuni.fi   
Turku University Hospital Not yet recruiting
Turku, Finland
Contact: Otto Ettala, MD, PhD       otto.ettala@utu.fi   
Sponsors and Collaborators
Tampere University Hospital
Turku University Hospital
Central Finland Hospital District
Tartu University Hospital
University of Aarhus
Fimlab laboratories
Helsinki University Central Hospital
Kuopio University Hospital
Investigators
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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

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Responsible Party: Teemu Murtola, MD, PhD, professor, Tampere University Hospital
ClinicalTrials.gov Identifier: NCT04026230     History of Changes
Other Study ID Numbers: 2016-004774-17
First Posted: July 19, 2019    Key Record Dates
Last Update Posted: September 11, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Sharing of individual-level data is not allowed by ethics board

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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
Keywords provided by Teemu Murtola, Tampere University Hospital:
Prostate cancer
Castration resistance
Cholesterol lowering drug
Cholesterol
Atorvastatin
Survival
Mortality
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Atorvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors