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Trial registered on ANZCTR


Registration number
ACTRN12617000965303
Ethics application status
Approved
Date submitted
22/06/2017
Date registered
5/07/2017
Date last updated
6/06/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Statins in Metastatic Castration-Resistant Prostate Cancer
Scientific title
Effect of Statins on a Prognostic Plasma Lipid Signature in Metastatic Castration-Resistant Prostate Cancer
Secondary ID [1] 292258 0
Nil known
Universal Trial Number (UTN)
U1111-1198-2546
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate cancer 303775 0
Condition category
Condition code
Cancer 303143 303143 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The aim of the study is to assess whether treatment with simvastatin during docetaxel chemotherapy for metastatic castration-resistant prostate cancer can reverse a poor prognostic plasma lipid signature.
Participants will be treated with simvastatin 40mg daily (oral tablet) for 12 weeks, at the same time as starting docetaxel chemotherapy.
Adherence to simvastatin will be assessed by investigators through regular clinic visits during treatment (every 3 weeks, at the same time as the pre-chemotherapy review).
Intervention code [1] 298424 0
Diagnosis / Prognosis
Intervention code [2] 298425 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 302516 0
Presence of a poor prognostic plasma lipid signature
- A previous study measured the global lipidomic profile in the plasma of men with metastatic castration-resistant prostate cancer starting docetaxel chemotherapy, using liquid chromatography and electrospray ionisation-tandem mass spectrometry (LC-MS/MS) (1)
- A three-lipid signature was derived which was prognostic for worse overall survival (1)
- This study will assess for the presence of this poor prognostic plasma lipid signature at baseline and after 12 weeks of simvastatin

1. Horvath L, et al. The plasma lipidome in castration-resistant prostate cancer. Poster presented at: American Society of Clinical Oncology Annual Meeting; 2017 June 2-6; Chicago, IL.
Timepoint [1] 302516 0
Baseline and after 12 weeks of intervention (simvastatin)
Secondary outcome [1] 336280 0
Incidence of adverse events using Common Terminology Criteria for Adverse Events (CTCAE) v4.03
- Particularly simvastatin related side effects such as myopathy, rhabdomyolysis and hepatic dysfunction
Timepoint [1] 336280 0
Monitored every 3 weeks throughout treatment and at a safety assessment 21-30 days following last dose of study treatment

Eligibility
Key inclusion criteria
1. Males with castration-resistant metastatic prostate cancer (as per PCWG3) AND commencing docetaxel chemotherapy for disease progression
2. Age 18 yrs or over
3. WHO ECOG performance status 0-2
4. Histological confirmation of prostate cancer
5. Adequate hepatic function with serum total bilirubin < 1.5 x upper limit of normal 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
6. 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;
7. Willing and able to comply with all study requirements, including treatment and biospecimen collection
8. Signed written informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients already receiving a lipid lowering agent(s), or have received one in the last 4 weeks
2. Known hypersensitivity to statins or its excipients
3. Prior myopathy with a lipid lowering agent
4. Active hepatic disease, including chronic active hepatitis B or hepatitis C. Testing for these is not mandatory unless clinically indicated.
5. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Single arm trial so no allocation required
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Single arm trial so no sequence generation required
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
This is a single arm, pilot study. Assuming 25% of patients have the poor prognostic lipid signature at baseline (as was found in our initial exploratory study), a total sample size of 60 participants provides over 90% power with a 1-sided type 1 error of 10% (with an allowance of 10% for inevaluable participants and missing data), to detect conversion to the good prognostic signature in 50% of patients.

A patient’s lipid signature will be analysed and classified as either good prognostic or poor prognostic as per our three-lipid signature model derived by logistic regression (as per our initial exploratory study). Rates of conversion from a poor prognostic signature to good prognostic will be analysed.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 8426 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [2] 8427 0
Concord Repatriation Hospital - Concord
Recruitment hospital [3] 8428 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [4] 8430 0
Ashford Cancer Centre: Adelaide Cancer Centre - Kurralta Park
Recruitment postcode(s) [1] 16498 0
2050 - Camperdown
Recruitment postcode(s) [2] 16499 0
2139 - Concord
Recruitment postcode(s) [3] 16500 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 16502 0
5037 - Kurralta Park

Funding & Sponsors
Funding source category [1] 296806 0
Charities/Societies/Foundations
Name [1] 296806 0
Movember Foundation
Address [1] 296806 0
PO Box 60
East Melbourne, VIC 8002
Country [1] 296806 0
Australia
Funding source category [2] 299694 0
Charities/Societies/Foundations
Name [2] 299694 0
ANZUP Below the Belt Research Fund
Address [2] 299694 0
Chris O'Brien Lifehouse
Level 6, 119-143 Missenden Road,
Camperdown NSW 2050
Country [2] 299694 0
Australia
Primary sponsor type
Hospital
Name
Chris O'Brien Lifehouse
Address
119-143 Missenden Road
Camperdown, NSW 2050
Country
Australia
Secondary sponsor category [1] 295792 0
None
Name [1] 295792 0
None
Address [1] 295792 0
None
Country [1] 295792 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298039 0
Sydney Local Health District Human Research Ethics Committee - CRGH
Ethics committee address [1] 298039 0
Concord Repatriation General Hospital (CRGH)
Concord, NSW 2139
Ethics committee country [1] 298039 0
Australia
Date submitted for ethics approval [1] 298039 0
12/04/2017
Approval date [1] 298039 0
16/06/2017
Ethics approval number [1] 298039 0
HREC/17/CRGH/97

Summary
Brief summary
This study aims to aims to test whether treatment with simvastatin during docetaxel chemotherapy for metastatic castration-resistant prostate cancer can reverse a poor prognostic plasma lipid signature.

Who is it for?
You may be eligible to join this study if you are a man aged 18 years or above diagnosed with metastatic castration-resistant prostate cancer and starting docetaxel chemotherapy shortly.

Study details
All study participants will be treated with simvastatin 40mg daily (oral tablet) for 12 weeks, at the same time as starting docetaxel chemotherapy. All participants will be followed up for 12 weeks to monitor safety and to assess the lipid profile using plasma samples.

It is hoped that this study will help answer the question of whether a 12 week course of a lipid-lowering drug called simvastatin (commonly used to treat high cholesterol, heart disease and diabetes) will lower the specific circulating lipids in blood that are associated with a worse prognosis in metastatic castration-resistant prostate cancer.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1825 1825 0 0
Attachments [2] 1826 1826 0 0

Contacts
Principal investigator
Name 75786 0
Prof Lisa Horvath
Address 75786 0
Chris O'Brien Lifehouse
119-143 Missenden Road
Camperdown NSW 2050
Country 75786 0
Australia
Phone 75786 0
+61 2 8514 0149
Fax 75786 0
Email 75786 0
lisa.horvath@lh.org.au
Contact person for public queries
Name 75787 0
Dr Blossom Mak
Address 75787 0
Chris O'Brien Lifehouse
119-143 Missenden Road
Camperdown NSW 2050
Country 75787 0
Australia
Phone 75787 0
+61 2 8514 0149
Fax 75787 0
Email 75787 0
blossom.mak@lh.org.au
Contact person for scientific queries
Name 75788 0
Prof Lisa Horvath
Address 75788 0
Chris O'Brien Lifehouse
119-143 Missenden Road
Camperdown NSW 2050
Country 75788 0
Australia
Phone 75788 0
+61 2 8514 0149
Fax 75788 0
Email 75788 0
blossom.mak@lh.org.au

No data has been provided for results reporting
Summary results
Not applicable