A clinical trial is being conducted to see the benefit of a known lipid-lowering drug such as pitavastatin in patients with advanced prostate cancer who are being treated with the new anti-androgens.
- Conditions
- 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.Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2022-000082-41-ES
- Lead Sponsor
- Fundación para la Investigación en Urología
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Male
- Target Recruitment
- 150
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)
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
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method