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Trial registered on ANZCTR


Registration number
ACTRN12624001458527
Ethics application status
Approved
Date submitted
31/10/2024
Date registered
16/12/2024
Date last updated
16/12/2024
Date data sharing statement initially provided
16/12/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of opaganib in addition to darolutamide in participants with metastatic hormone resistant prostate cancer, selected for the presence of a specific biomarker.
Scientific title
Randomised Phase 2 study of sphingosine kinase inhibitor (opaganib) in addition to darolutamide in people with poor prognostic metastatic castration resistant prostate cancer (mCRPC) based on a companion circulating lipid biomarker, PCPro (ANZUP2205)
Secondary ID [1] 313199 0
ANZUP Cancer Trials Group Ltd: ANZUP2205
Universal Trial Number (UTN)
Trial acronym
DARO-LIPID
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 335495 0
Condition category
Condition code
Cancer 332054 332054 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants with a poor prognostic circulating lipid profile (PCPro positive) who are randomised to Arm A will be instructed to take two tablets of darolutamide, and two capsules of opaganib orally twice daily with food. Each cycle is defined as 4 weeks. On treatment assessments will be performed for all participants within 5 days of day 1 dosing of each cycle and treatment will continue until no longer clinically beneficial, unacceptable toxicity or participant preference. Participants will be asked to return drug bottes at scheduled clinic visits as per the protocol. Pharmacists will be conducting a count of the remaining tablets to monitor participant's adherence to the intervention. Any discrepancies in the count will be reviewed and discussed with the participant to ensure compliance with the study protocol.
Arm A: Darolutamide 600mg twice daily + Opaganib 500mg twice daily
Intervention code [1] 329799 0
Treatment: Drugs
Comparator / control treatment
Participants with a poor prognostic circulating lipid profile (PCPro positive) who are randomised to Arm B will be instructed to take two tablets of darolutamide, and two capsules of placebo orally twice daily with food. Each cycle is defined as 4 weeks. On treatment assessments will be performed for all participants within 5 days of day 1 dosing of each cycle and treatment will continue until no longer clinically beneficial, unacceptable toxicity or participant preference. Participants will be asked to return drug bottes at scheduled clinic visits as per the protocol. Pharmacists will be conducting a count of the remaining tablets to monitor participant's adherence to the intervention. Any discrepancies in the count will be reviewed and discussed with the participant to ensure compliance with the study protocol.
Arm B: Darolutamide 600mg twice daily + Placebo 500mg twice daily
Control group
Active

Outcomes
Primary outcome [1] 339683 0
12 month Radiogaphic Progression Free Survival (rPFS)
Timepoint [1] 339683 0
This will be assessed at baseline and every 12 weeks until 12 month post treatment commencement OR every 12 weeks until disease progression.
Secondary outcome [1] 440870 0
PSA Progression-Free Survival
Timepoint [1] 440870 0
PSA will be assessed at baseline, every 4 weeks while on study treatment, at end of treatment (within 7 days +/- 7 days of last treatment administration), 30 days +/- 5 days of last treatment administration.
Secondary outcome [2] 440871 0
Overall survival
Timepoint [2] 440871 0
Through to completion of follow up; survival follow up will occur every three months +/- 21 days after disease progression.
Secondary outcome [3] 440872 0
Frequency and severity of adverse events - composite outcome
Timepoint [3] 440872 0
Baseline, every 4 weeks while on study treatment, end of treatment (within 7 days +/-7 days of last treatment administration), safety assessment (30 days +/-5 days of last treatment administration).
Secondary outcome [4] 440873 0
Health Related Quality of Life (HRQL)
Timepoint [4] 440873 0
Baseline, every 12 weeks +/-5 days from day 1 cycle 1 until disease progression, end of treatment (within 7 days +/- 7 days of last treatment administration) and safety assessment (within 7 days +/-7 days of last treatment administration (30 days +/- 5 days of last treatment administration).
Secondary outcome [5] 440874 0
Health economics to evaluate cost effectiveness
Timepoint [5] 440874 0
Health economic analysis will be conducted at the end of the study.
Secondary outcome [6] 440876 0
Change in circulating lipid profile with opaganib treatment
Timepoint [6] 440876 0
In addition to analysis at pre-screening, PCPro will be determined after 12 weeks and at progression.
Secondary outcome [7] 441772 0
Health economics - QALY
Timepoint [7] 441772 0
Health economic analysis will be conducted at the end of the study.
Secondary outcome [8] 442247 0
Change in circulating lipid profile with opaganib treatment
Timepoint [8] 442247 0
Analysis will be performed at baseline, after 12 weeks on study treatments and at progression.

Eligibility
Key inclusion criteria
1 Metastatic adenocarcinoma of the prostate defined as
*Documented histopathology of prostate adenocarcinoma (no features of neuroendocrine
carcinoma)
OR
*Metastatic disease typical of prostate cancer
2 Castration-resistant prostate cancer (defined as disease progressing despite castration by
orchiectomy or ongoing luteinizing hormone-releasing hormone agonist or antagonist)
3 Progressive disease with rising PSA defined by PCWG3 criteria (sequence of 2 rising
values at a minimum of 1-week intervals) or progression of disease radiologically
4 Evidence of metastases on bone scan and/or CT scan beyond pelvic lymphadenopathy
5 Participants are allowed to have had previous chemotherapy with docetaxel in the
hormone sensitive setting only
6 Acceptable liver function:
*Bilirubin less than or equal to 1.5 times upper limit of normal (CTCAE Grade 1 baseline)
*AST (SGOT) & ALT (SGPT) less than or equal to 3 x upper limit of normal (ULN) (CTCAE
Grade 1 baseline)
*Participants with Gilbert's syndrome may be included if the total bilirubin is less than 3x
ULN and the direct bilirubin is within normal limits
7 Acceptable kidney function indicated by serum creatinine less than or equal to 1.5 X ULN
(CTCAE Grade 1 baseline)
8 Acceptable hematologic status:
*Absolute neutrophil count is greater than or equal to 1.0 x 109 /L
*Platelet count is equal to or greater than or equal to 75 x 109/L (CTCAE Grade 1 baseline)
*Hemoglobin is greater than or equal to 90 g/L
9 ECOG performance status 0-1
10 Life expectancy of at least 3 months
11 Willing to complete all study requirements, including standard of care treatment
12 Willing to complete Health Related quality of life (HRQL) questionnaires UNLESS is
unable to complete because of literacy or limited vision
13 Signed, written informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1 Prostate cancer with known significant sarcomatoid, spindle cell, or neuroendocrine small
cell components, or metastasis of other cancer to the prostate
2 Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral
absorption or tolerance of darolutamide or opaganib, including difficulty swallowing
tablets
3. Any prior use of Androgen Receptor pathway inhibitors (abiraterone, enzalutamide,
apalutamide, darolutamide or similar agents)
4. Prior use of chemotherapy in the castration resistant prostate cancer setting
5. People who are receiving opioid-based medications
6. New York Heart Association Class III or IV, cardiac disease, myocardial infarction within
the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG
7. Active, uncontrolled bacterial, viral or fungal infection, requiring systemic therapy
8. Treatment with radiation therapy, surgery, or investigational therapy within 14 days prior
to registration
9. Participants who are receiving coumadin, apixaban, argatroban or rivaroxaban.
Participants who are receiving other drugs that are sensitive substrates of CYP450 1A2,
3A4, 2C9, 2C19 or 2D6, or strong inhibitors or inducers of all major CYP450 isozymes that
cannot be stopped at least 7 days or 5 half-lives (whichever is longer) before starting
treatment with opaganib may be treated on this study with careful monitoring for toxic
effects or loss of efficacy of the relevant drug.
10. Participants with underlying psychiatric disorders requiring hospitalization within the last
2 years
11. Clinically significant neurological disorders (Parkinson’s disease, dementia, multiple
sclerosis) as determined by the enrolling investigator
12. Concurrent participation in other clinical trials of investigational agents for the treatment
of prostate cancer or other diseases
13. People with history of hypersensitivity to the study treatments

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/01/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 317645 0
Charities/Societies/Foundations
Name [1] 317645 0
Ramsay Foundation
Country [1] 317645 0
Australia
Funding source category [2] 317669 0
Commercial sector/Industry
Name [2] 317669 0
Bayer Australia Limited
Country [2] 317669 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Address
Country
Australia
Secondary sponsor category [1] 319986 0
None
Name [1] 319986 0
Address [1] 319986 0
Country [1] 319986 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316344 0
St Vincent’s Hospital Human Research Ethics Committee
Ethics committee address [1] 316344 0
Ethics committee country [1] 316344 0
Australia
Date submitted for ethics approval [1] 316344 0
26/08/2024
Approval date [1] 316344 0
16/10/2024
Ethics approval number [1] 316344 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 137594 0
Prof Lisa Horvath
Address 137594 0
Chris O'Brien LifeHouse, 119-143 Missenden Road, Camperdown, NSW 2050, PO Box M5, Missenden Road, NSW 2050
Country 137594 0
Australia
Phone 137594 0
+61 2 8514 0142
Fax 137594 0
Email 137594 0
lisa.horvath@lh.org.au
Contact person for public queries
Name 137595 0
Archana Nair
Address 137595 0
Australian and New Zealand Urogenital and Prostate Cancer Trials Group Limited, Level 18, Tower 3, 300 Barangaroo Avenue, Barangaroo, NSW 2000
Country 137595 0
Australia
Phone 137595 0
+61 2 9054 3600
Fax 137595 0
Email 137595 0
trials@anzup.org.au
Contact person for scientific queries
Name 137596 0
Archana Nair
Address 137596 0
Australian and New Zealand Urogenital and Prostate Cancer Trials Group Limited, Level 18, Tower 3, 300 Barangaroo Avenue, Barangaroo, NSW 2000
Country 137596 0
Australia
Phone 137596 0
+61 2 9054 3600
Fax 137596 0
Email 137596 0
trials@anzup.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.