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Trial registered on ANZCTR


Registration number
ACTRN12622001003763
Ethics application status
Approved
Date submitted
18/06/2022
Date registered
18/07/2022
Date last updated
9/10/2023
Date data sharing statement initially provided
18/07/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Evolocumab in Metastatic Castration-Resistant Prostate Cancer
Scientific title
A multi-centre, open label phase 2 trial investigating the effect of evolocumab in addition to chemotherapy or androgen receptor signalling inhibitor therapy on the circulating lipid profile of men with metastatic castration-resistant prostate cancer
Secondary ID [1] 307385 0
Protocol Number: X22-0072
Universal Trial Number (UTN)
U1111-1279-5669
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Castrate Resistant Prostate Cancer 326697 0
Condition category
Condition code
Cancer 323943 323943 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be asked to take evolocumab 420 mg via subcutaneous injection every 4 weeks, for 12 weeks, commencing on day 1 of the first dose of chemotherapy or Androgen receptor signaling antagonists (ARSI) therapy.

Evolocumab will be prescribed via an electronic medical chart (EMR) and administered by a clinical trials nurse at scheduled trial visits to ensure adherence, as per the trial protocol. General lipid levels will also be monitored via routine biochemistry during the trial.

ARSI's will be administered via the oral route and chemotherapy will be administered via an intravenous infusion. All dosing and frequency decisions regarding ARSI and chemotherapy will be made at the discretion of the participant's treating doctor and will be unchanged by their involvement in this study.
Intervention code [1] 323820 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 331743 0
Change in circulating lipid profile assessed by measuring levels of ceramides in a blood sample with the concomitant use of evolocumab in men commencing chemotherapy (docetaxel or cabazitaxel) or ARSI therapy (abiraterone or enzalutamide) for metastatic castrate resistant prostate cancer (mCRPC).

Timepoint [1] 331743 0
Baseline and at 12 weeks post-treatment commencement
Secondary outcome [1] 410972 0
Change in PSA levels assessed using a blood sample
Timepoint [1] 410972 0
Baseline and at 12 weeks post-treatment commencement
Secondary outcome [2] 410973 0
Adverse events (worst grade according to National cancer institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

The proportion of patients experiencing treatment-related toxicities, as defined by the Common Toxicity Criteria v4.0 of the National Cancer Institute (NCI CTC v4.03) and reporting of Serious Adverse Events (SAEs). The NCI CTCAE v4.03 will be used to classify and grade the intensity of adverse events after each dose of evolocumab.
Timepoint [2] 410973 0
This outcome will be assessed at 4, 8, and 12 weeks following evolocumab treatment commencement.

Eligibility
Key inclusion criteria
1. Males with mCRPC (as per prostate cancer working group (PCWG3)) AND commencing docetaxel, cabazitaxel, abiraterone or enzalutamide for disease progression
2. Age > 18 yrs
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 (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
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. Demonstrated positivity for high-risk circulating plasma lipid profile on Liquid chromatography–mass spectrometry (LCMS)
8. Willing and able to comply with all study requirements, including treatment and biospecimen collection
9. Signed written informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known hypersensitivity to evolocumab or its excipients
2. Prior myopathy with a lipid lowering agent
3. Active hepatic disease, including chronic active hepatitis B or hepatitis C. Testing for these is not mandatory unless clinically indicated.
4. 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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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
Sample Size
Based on our previous data, around 35% of patients will have the poor prognostic lipid signature at baseline. A total sample size of 30 patients with the poor prognostic lipid signature will provide over 80% power with a type 1 error of 10% to reject the null hypothesis of conversion to the good prognostic signature of <30% if the true probability is at least 50%.

Statistical analysis
A patient’s lipidomic profile will be analysed for the poor prognostic signature as per our poor prognostic lipid signature model derived by logistic regression.


Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
14/02/2023
Actual
8/03/2023
Date of last participant enrolment
Anticipated
30/06/2024
Actual
Date of last data collection
Anticipated
1/08/2024
Actual
Sample size
Target
30
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 22584 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [2] 22585 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [3] 25718 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 37838 0
2050 - Camperdown
Recruitment postcode(s) [2] 37839 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 41542 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 311662 0
Government body
Name [1] 311662 0
National Health and Medical Research Council
Country [1] 311662 0
Australia
Primary sponsor type
Government body
Name
National Health and Medical Research Council
Address
16 Marcus Clarke St, Canberra ACT 2601
Country
Australia
Secondary sponsor category [1] 313113 0
None
Name [1] 313113 0
Address [1] 313113 0
Country [1] 313113 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311119 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 311119 0
Research Ethics and Governance Office (REGO)
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050
Ethics committee country [1] 311119 0
Australia
Date submitted for ethics approval [1] 311119 0
10/06/2022
Approval date [1] 311119 0
24/06/2022
Ethics approval number [1] 311119 0
X22-0072 & 2022/ETH00427

Summary
Brief summary
Elevated lipids called ceramides are associated with poorer outcomes in men with prostate cancer. 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 antibody (PCSK9) inhibitor evolocumab may be required. This study aims to assess whether evolocumab reduces ceramide levels in men with mCRPC commencing chemotherapy or androgen receptor signaling inhibitors (ARSI) therapy.

Who is it for?
You may be eligible for this study if you are aged 18 years or over, have been diagnosed with mCRPC, and are planned to commence chemotherapy (docetaxel or cabazitaxel) or ARSI therapy (abiraterone or enzalutamide).

Study details
All participants will receive 420mg of evolocumab administered subcutaneously (i.e. injected under the skin) every 4 weeks for 12 weeks, commencing on day 1 of the first dose of chemotherapy or ARSI therapy. After each dose of evolocumab, participants will be monitored for any side effects. Blood samples will also be taken at baseline and after 12 weeks of treatment to assess for changes in the circulating lipid profile (i.e. ceramide levels) and prostate-specific antigen (PSA) levels.

It is hoped that this study may show that evolocumab reduces ceramide levels associated with poor prognosis in men with mCRPC.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120002 0
Prof Lisa Horvath
Address 120002 0
Chris O’Brien Lifehouse
119-143 Missenden Road
Camperdown NSW 2050
PO BOX M5 Missenden Road NSW 2050
Country 120002 0
Australia
Phone 120002 0
+61 2 85140142
Fax 120002 0
Email 120002 0
[email protected]
Contact person for public queries
Name 120003 0
Lisa Horvath
Address 120003 0
Chris O’Brien Lifehouse
119-143 Missenden Road
Camperdown NSW 2050
PO BOX M5 Missenden Road NSW 2050
Country 120003 0
Australia
Phone 120003 0
+61 2 85140142
Fax 120003 0
Email 120003 0
[email protected]
Contact person for scientific queries
Name 120004 0
Lisa Horvath
Address 120004 0
Chris O’Brien Lifehouse
119-143 Missenden Road
Camperdown NSW 2050
PO BOX M5 Missenden Road NSW 2050
Country 120004 0
Australia
Phone 120004 0
+61 2 85140142
Fax 120004 0
Email 120004 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Concern regharding fault in the patient identity protection caused by the transmission of sensitive information.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.