Brief Summary
Elevated lipids called ceramides are associated with poorer outcomes in men with prostatea walnut-shaped gland in the male reproductive system that is responsible for producing semen - a bodily fluid that acts as a vessel for sperm transport during ejaculation cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs. Statins, a class of drug that reduces lipid levels, have been shown to be somewhat helpful in reversing this poor prognostic lipid signature, however only in a subset of men with metastatic castration-resistant prostate cancer (mCRPC) (i.e. those that are resistant to anti-androgen treatment). Therefore, other more potent or targeted lipid lowering drugs such as the anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodya protein made by the immune system to fight against harmful substances (antigens), such as bacteria or viruses (PCSK9) inhibitor evolocumab may be required. This study aims to assess whether evolocumab reduces ceramide levels in men with mCRPC commencing chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells or androgen receptor signaling inhibitors (ARSI) therapy.
Intervention/Treatment
- Drug: Evolocumab.
- Chemotherapy.
- Androgen receptor signaling inhibitor (ARSI) therapy.
- Poly ADP ribose polymerase inhibitor (PARPI) therapy.
- Lutetium-177 prostatespecific membrane antigen (PSMA) therapy.
Inclusion Criteria:
- Males with mCRPC (as per prostate cancer working group (PCWG3)) AND commencing docetaxel, cabazitaxel, abiraterone or enzalutamide, olaparib or lutetium for disease progression.
- Age > 18 yrs.
- WHO ECOG performance status 0-2.
- Histological confirmation of prostate cancer.
- Adequate hepatic function with serum total bilirubin > 1.5 x upper limit of normal (ULN) range and ALT and AST > 2.5x upper limit of normal range (or < 5.0 times ULN with documented liver metastases), serum albumin > 25 g/L, and ALP > 5x upper limit of normal range.
- Adequate renal function (with calculated creatinine clearance >50 ml/min based on the Cockcroft-Gault method, 24 hour urine or GFR scan) and serum creatinine > 1.5 x upper limit of normal range.
- Demonstrated positivity for high-risk circulating plasma lipid profile on Liquid chromatography–massa growth of cells that come together to make a lump, may or may not be cancer spectrometry (LCMS).
- Willing and able to comply with all study requirements, including treatment and biospecimen collection.
- Signed written informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment..