Evaluation of Atorvastatin on Progression of Metastatic or High-Risk Recurrent Prostate Cancer During Androgen Deprivation Therapy: A Phase 3 Randomized Controlled Trial

The primary objective of this phase 3, double-blind randomized clinical trial is to evaluate whether intervention with **atorvastatin** delays the progression of **prostate cancer**, specifically the development of castration resistance, compared to placebo during androgen deprivation therapy (ADT) for advanced prostate cancer. This is clinically relevant as delaying castration resistance can potentially improve patient outcomes and extend the effectiveness of ADT in managing metastatic or high-risk recurrent prostate cancer.

The clinical trial involves a study population consisting exclusively of **male** participants diagnosed with **metastatic or high-risk recurrent prostate cancer**. The participants are undergoing androgen deprivation therapy. The age range of the participants falls within the categories of 45 to 64 years and 65 to 84 years. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. The selection criteria for the trial population include histopathologically confirmed metastatic adenocarcinoma of the prostate, with radiologically confirmed bone or soft tissue metastasis or enlarged lymph nodes beyond the pelvic region. Participants must have initiated androgen deprivation or antiandrogen therapy no longer than three months prior to recruitment. The trial excludes female subjects and does not focus on any specific lifestyle considerations such as diet or physical activity. Key inclusion criteria involve high-risk M0 stage prostate cancer recurring after curative-intent primary therapy, with specific conditions such as a Gleason score of 8-10, PSA doubling time of 6 months or less, PSA levels of 20 ng/ml or higher, or new lymph node metastases in imaging.

The clinical trial is designed to evaluate the impact of **atorvastatin** on the progression of prostate cancer in patients undergoing androgen deprivation therapy. This is a phase III, double-blind, randomized, controlled trial. The trial aims to determine whether intervention with atorvastatin delays the development of castration resistance compared to a placebo. The study is expected to run from May 2018 to December 2033, with the primary endpoint being the time to disease progression after starting androgen deprivation or antiandrogen therapy.

Participants will be randomly assigned to receive either atorvastatin or a placebo, both administered orally in the form of film-coated tablets. The maximum daily dose of atorvastatin is 80 mg, with a total treatment period of up to 120 days. The trial will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor disease progression and treatment response, and an end-of-study visit to assess final outcomes. The inclusion criteria require histopathologically confirmed metastatic adenocarcinoma of the prostate or high-risk recurrent prostate cancer, with androgen deprivation therapy initiated no longer than three months prior to recruitment.

Participant involvement is expected to last until the end of the study or until disease progression, whichever occurs first. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or any other medical condition that, in the investigator's opinion, warrants discontinuation. The trial is not classified as low intervention, and it is conducted under strict adherence to ethical guidelines and regulatory requirements.

The clinical trial involves the administration of **Atorvastatin**, a cholesterol-lowering medication, as the experimental treatment. The specific formulation used is **Atorvastatin Krka 40 mg film-coated tablets**. The active substance in this medication is atorvastatin, which is of chemical origin. The tablets are administered orally, with a maximum daily dose of 80 mg and a total maximum dose of 292 grams over the course of the study. The treatment period is set for a maximum of 120 days. The tablets have undergone over-encapsulation to ensure blinding in the study. The pharmaceutical form is a film-coated tablet, and the product is authorized in Finland under the marketing authorization number 23451.

The study also includes a **placebo** group, which receives an identical capsule to the active product but without any active ingredient. This placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators know which treatment is being administered. The placebo capsules are designed to match the appearance of the atorvastatin tablets to prevent bias in the study results. The placebo does not contain any active substances and is not associated with any specific pharmaceutical form or marketing authorization.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the time to disease progression after starting androgen deprivation therapy (ADT) or antiandrogen therapy in patients with advanced prostate cancer. The trial aims to determine whether intervention with **atorvastatin** delays prostate cancer progression, specifically the development of castration resistance, compared to a placebo. The assessment of efficacy will involve monitoring the progression of prostate cancer in participants who are receiving atorvastatin in conjunction with ADT.