SPECTRE study - A study looking at Combined SuPpression of cholEsterol bioavailability and androgen deprivation therapy to treat CastraTion Resistant prostatE cancer
Issued: Thu, 15 Dec 2016 11:44:00 GMT
SPECTRE - A study looking at Combined SuPpression of cholEsterol bioavailability and androgen deprivation therapy to treat CastraTion Resistant prostatE cancer
Background: Why are we undertaking the SPECTRE study?
The role of statins in the development of prostate cancer (PC) and its progression is hotly debated.
While there is significant controversy concerning whether statins might reduce the overall risk for PC, there is a growing body of evidence to suggest that the use of statins post-diagnosis influences the outcome of patients with lethal PC, reducing cancer mortality rate by as much as 39% in men taking statins at least for 3 years post-diagnosis while the incidence of metastases were reduced by 23%. A similar conclusion was made in an independent report. Furthermore, individuals with elevated total serum cholesterol and triglycerides are at increased risk of developing aggressive prostate cancer (PC) with a reduced disease free survival.
Atorvastatin is currently licensed for, and widely used in the treatment of hypercholesterolemia and the prevention of cardiovascular disease. There are no previous trials of atorvastatin specifically as a treatment for prostate cancer.
Review (or retrospective evaluation) of previous published research on selected patient populations showed that individuals using statins after the initial diagnosis of prostate cancer tend to have lower risks of cancer recurrence following hormone manipulation treatment. Interpretation of such retrospective studies is always difficult; many unrelated reasons can influence the outcome, resulting in spurious associations. Those individuals taking statins may also be affected by other medical conditions including obesity, diabetes and high blood pressure, for which they will have treatments. Any apparent relationship between statins and prostate cancer progression may result from unrelated factors.
Another urgent unmet need in prostate cancer management is the lack of a sensitive and accurate method to report on the cancer status. Often patients’ routine Prostate Specific Antigen (PSA) blood tests for prostate cancer may suggest excellent initial response to treatment such as hormone manipulation to achieve ADT. However, such optimism would prove short-lived with subsequent rise in the PSA levels. The SPECTRE study will apply the state-of-art technology to see if markers in blood and prostate tissue may help to ‘track’ the status of the cancer more accurately.
Hypothesis: Inhibition of cholesterol biosynthesis in patients with ongoing ADT will suppress CRPC via a reduction in androgen mediated signalling.
Design: Single arm Phase II. The study population will be 35 evaluable patients with castration resistant prostate cancer, to be recruited at the Beatson West of Scotland Cancer Centre
Primary objective: To explore the impact of atorvastatin on androgen receptor signalling in castration-resistant prostate cancer.
Secondary objective - To study the impact of atorvastatin on the status of intermediates of androgen biosynthesis pathway in castration-resistant prostate cancer.
Exploratory objective - To explore potential impact of atorvastatin on molecular biomarkers in men with castration-resistant prostate cancer.
Research blood samples will be collected from eligible patients prior to the start of atorvastatin medication, and weekly for up to 6 weeks.
Tumour biopsy samples will be collected from approximately 15 study patients. The first sample will be collected prior to the start of atorvastatin and a second will be collected after 5-7 weeks of atorvastatin medication.
Analysis of the study samples will be performed at Clinical Chemistry Department, Glasgow Biobank, NHS GGC, and the Beatson Institute, University of Glasgow:
Investigative tests: PSA, testosterone, total cholesterol, HDL/LDL, DHEA, cholesterol esters, liver function tests (ALT; GGT), glucose, triglycerides, free fatty acids, insulin.
Metabolic profiling – NMR Metabolomics samples.
Planned analysis will include:
Change in adrenal steroid DHEA (dehydroepiandrosterone) levels
Reduction in levels of circulating cell-free tumour DNA (ctDNA) and/or circulating exosomes and/or circulating tumour cells (CTC) from serial blood samples obtained before and during exposure to atorvastatin, and changes in intra-tumoural metabolic intermediates for androgen bio-synthesis.
Who can enter SPECTRE?
Male Patients over 18 years may be able to join this study if they have histologically proven adenocarcinoma of the prostate (patients may or may not have evidence of metastatic disease, and disease progression despite on-going castration therapy (either using LHRH analogue or prior surgical orchiectomy) as judged by rising serial PSA measurements
Potential patients must not have received therapy with statins or other cholesterol-lowering drug during a 2-month period prior to initiation of trial medication.
SPECTRE will launch in November 2016 and patients will be recruited for 2 years.
Who is funding and managing SPECTRE?
The study has received grant funding from Prostate Cancer UK, and is co-ordinated by the Cancer Research Clinical Trials Office, Glasgow. It is Co-sponsored by the University of Glasgow and NHS Greater Glasgow and Clyde
Chief Investigator – Professor Hing Leung
NHS Greater Glasgow and Clyde
University of Glasgow
Prostate Cancer UK (PCUK)
Cancer Research UK, Clinical Trials Unit, Glasgow (CRUK CTU)
How do I find out more about SPECTRE?
If you would like further information about the SPECTRE study, please contact the study team:
Chief Investigator: Professor Hing Leung Email: firstname.lastname@example.org
Project Manager: Laura Alexander Email: email@example.com
Clinical Trial Co-ordinator: Avril Trevethan Email: firstname.lastname@example.org