We propose a multicenter, prospective, randomized, single-blind clinical trial, without conflict of interest, to determine the clinical benefit of statins (Pitavastatin 2 mg) in prostate cancer patients being treated with ARTA (enzalutamide, apalutamide, darolutamide and abiraterone). As primary objectives we will determine whether in the experimental group an increase in metastasis-free survival and radiological progression-free survival is achieved.
Conditions
Interventions
Trade Name: Pitavastatin: Livazo 2 mg
Product Name: Pitavastatin
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Buccal use
Sponsors
Fundación para la Investigación en Urología
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Patients with a histological diagnosis of prostate cancer, who are in one of the clinical stages listed in the inclusion criteria. listed in the inclusion criteria a) Inclusion criteria: Patients with hormone-sensitive metastatic prostate cancer (HSPCm), who have not received previous line a.1. Patients with hormone-sensitive metastatic prostate cancer (HSPC), who have not received previous superantiandrogens or chemotherapy. a.2. Patients with metastatic castration-resistant prostate cancer (mCRPC), who have not received previous a.2. Patients with metastatic castration-resistant prostate cancer (mCRPC), who have not received previous superantiandrogens or chemotherapy. The criteria defining castration-resistant prostate cancer are: - Three consecutive PSA elevations, separated by at least one week, with two 50% increments above nadir and provided that this increase results in a PSA greater than 2 ng/ml. - Testosterone levels below 50 ng/dl or 1.7 nmol/l. - Progression of bone lesions = 2 on bone scan or progression of soft tissue lesions according to the RECIST criteria. RECIST criteriaa. 3. Non-metastatic castration-resistant prostate cancer (CRPCnm) and high-risk prostate cancer patients (PSA doubling time < 6 months). Patients with PCa will be treated with one of these 4 active drugs for their disease: a.4. disease: -Abiraterone -Enzalutamide -Apalutamide -Darolutamide a.5 Drug to be studied (dependent variable): pitavastatin 2 mg. It should be taken into account that enzalutamide is a potent inducer of cytochrome CYP3A4 and may interact with statins. Differences in hepatic metabolism of statins are of great importance, as they are the main cause of the different interactions between statins and statins. the main cause of the different interactions of these drugs. Thus, atorvastatin, lovastatin and simvastatin are metabolised by isoform 3. metabolised by the 3A4 isoform of cytochrome P450 (CYP3A4), and some drugs can substantially increase the plasma levels of these statins. plasma levels of these statins and, as a consequence, increase the risk of myopathies. Similarly, there are enzyme inducers that will decrease their pharmacological effect (1-3) , such as enzalutamide. Therefore, the statin chosen for the study is pitavastatin since its concentration according to in vitro and in vivo data indicates that it is not is metabolised by the 3A4 isoform of cytochrome P450 in a clinically significant amount, making it the statin with the fewest interactions. statin with the fewest interactions. On the other hand, due to its lipophilic structure it has a wide bioavailability, and can be found in significant concentrations in prostate cells (4) . 1.Franco D, Henao Y, Monsalve M, et al. Hypolipidemic agents drug interactions: approach to establish and assess its clinical significance. its clinical significance. Structured review. Farm Hosp. 2013 Nov-Dec;37(6):539-57. 2. Ríos González E, Martínez-Piñeiro L. Enzalutamide in castration resistant prostate cancer. Arch Esp Urol. 2018 Sep;71(8):664-675. Narayanan R, Hoffmann M, Kumar G, et al. Application of a "Fit for Purpose" PBPK Model to Investigate the CYP3A4 Induction Potential of CYP3A4. CYP3A4 Induction Potential of Enzalutamide. Drug Metab Lett. 2016;10(3):172-179. 4. Ahmad H, Cheng-Lai A. Pitavastatin: a new HMG-CoA reductase inhibitor for the treatment of hypercholesterolemia. Cardiol Rev. 2010 Sep-Oct;18(5):264-7. Are the trial subjects under 18? no Numbe
Exclusion criteria
Exclusion criteria: Exclusion criteria: Patients with hyperlipidaemia at the time of diagnosis whether or not under pharmacological treatment; b.2. b.2. Patients with transaminase levels twice the normal value. b.3. Patients in whom information on the variables under study is not available. b.4. Patients who refuse to take part in the study or do not sign the informed consent form.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 2-3 years;Main Objective: Primary objective: to determine whether in the pitavastatin treatment group there is an increase in metastasis-free survival and/or radiological progression-free survival (RFS). free survival and/or radiological progression free survival (rPFS) in the pitavastatin treatment group. We evaluated metastasis-free survival in the group of patients in the group of patients with high-risk non-metastatic castration-resistant prostate cancer (mCRPC) and defined it as the time to onset of metastasis. defined as the time until the appearance of the first metastasis and thus change of clinical stage to metastatic CRPC. metastatic. PrFS is assessed in the groups of patients who are already metastatic, i.e. in the group of hormone-sensitive and hormone-resistant patients. and castration-resistant patients and is defined as the time to the appearance of a new metastasis. metastasis.;Secondary Objective: Secondary objectives: to determine whether the pitavastatin treatment group has an increase in overall survival and a decrease in the risk of cardiovascular events vs. survival and a decrease in the risk of cardiovascular events compared to the control group (placebo) and if there are also changes in the biochemical parameters of testosterone, PSA and modifications in the biochemical parameters of testosterone, PSA and a modulation of the inflammatory response through the modification of the inflammatory response by modifying the following haematological parameters: neutrophil/lymphocyte ratio (NL/RN/L), platelet ratio (NR/L), platelet/lymphocyte ratio (PL/L), systemic inflammatory index (SII).;Primary end point(s): Primary objective: to determine whether in the pitavastatin treatment group there is an increase in metastasis-free survival and/or radiological progression-free survival (RFS). free survival and/or radiological progression free survival (rPFS) in the pitavastatin treatment group. We eval | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary objectives: to determine whether the pitavastatin treatment group has an increase in overall survival and a decrease in the risk of cardiovascular events vs. survival and a decrease in the risk of cardiovascular events compared to the control group (placebo) and if there are also changes in the biochemical parameters of testosterone, PSA and modifications in the biochemical parameters of testosterone, PSA and a modulation of the inflammatory response through the modification of the inflammatory response by modifying the following haematological parameters: neutrophil/lymphocyte ratio (NL/RN/L), platelet ratio (NR/L), platelet/lymphocyte ratio (PL/L), systemic inflammatory index (SII).;Timepoint(s) of evaluation of this end point: 2-3 years | — |
Countries
Spain
Contacts
Public ContactFIU
Asociación Española de Urología
Outcome results
None listed