Cholesterol Lowering Induced Prolonged Castration Inhibition Effect (Castration-Resistance Delay) May Navigate the Prostate Cancer Spread or Progress after Androgen Deprivation Therapy: Randomized double-blind phase 3 clinical study protocol for North Ind

Abstract

Cholesterol lowering in blood by use of statins is a standard approach while blood cholesterol also poses a risk of recurrent prostate cancer prognosis among post-prostatectomy survivors with cardiac disease. Recently cardioprotective statins were associated with reducing risk of prostate cancer recurrence in post-treated progressive prostate cancer. In fact, statins performs two functions: 1. Statins prolong the time period to initiate the castration resistance during androgen deprivation therapy for prostate cancer; 2. Statins biosense or navigate the prostate cancer spread as predictor of the patient outcome.  The proposed study protocol will test the statin action on delaying castration-resistance in a randomized placebo-controlled manner.

Aim: The study protocol aims two objectives: 1. to compare different statins’ efficacy vs placebo to test the castration-resistance delay before development of castration resistance during androgen deprivation therapy for primary metastatic or recurrent prostate cancer; 2. to navigate the statin intervention effects to improve better patient outcome as less prostate cancer mortality and cholesterol lowering metabolism during ADT.

Materials and Methods: A randomized placebo-controlled trial of 500 male subjects with de novo metastatic or recurrent prostate cancer after routine and androgen deprivation therapy.  Dosage: A daily 80 mg atorvastatin or placebo dose will be administered in randomized 1:1 subjects in atorvastatin or placebo control groups while keeping blind all nurses, researchers and patients throughout the study period. All these patients will be followed up until cancer Here biosensing indicator is beginning of castration resistance after androgen deprivation therapy as primary outcome.  The serum lipid profile (total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides) serves as cholesterol-lowering predictor of treatment response during androgen deprivation therapy. Additional comparable benefit of statins may be on improved LONGLIVE lifestyle (less cardiovascular morbidity, normal blood sugar, circulating cell-free DNA, urine lipidome) 

Patient Ethics:  The study will be approved by institution ethics committee of Government Medical College, Saharanpur UP, India and Massachusetts General Hospital, Boston MA (Applied for). All subjects will read and sign informed consent form before study entry.  After publication of results for the primary endpoints, anonymous summary metadata and statistical code will be made available to all without any information of participating patients. 

Clinical Study Registration Number: ICMR/IITR-GMC Academy 2024/PC-003