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

Tampere University Hospital

Status and phase: Enrolling; Phase 3

Conditions: Metastatic Prostate Cancer; Recurrent Prostate Cancer

Treatments: Drug: Atorvastatin 80mg; Drug: Placebo oral capsule

Study type: Interventional

Funder types: Other

Identifiers

NCT04026230

2016-004774-17

Details and patient eligibility

About

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.

Full 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.

Enrollment: 400 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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400 participants in 2 patient groups, including a placebo group

Atorvastatin

Experimental group

Description:

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

Treatment:

Drug: Atorvastatin 80mg

Placebo

Placebo Comparator group

Description:

Identical capsules as in the atorvastatin arm, but including no active ingredient. Used daily for max. 10 years or until development of castration resistance

Treatment:

Drug: Placebo oral capsule