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RecruitingLast updated: 10 April 2026

DARO-LIPID: This study is recruiting people with metastatic hormone resistant prostate cancer to test whether a new approach to using predictive biomarkers to select people for targeted treatment can overcome hormone resistanceRandomised 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

Trial purpose

Medical clipboardCancer treatment

Tumor type

Urinary System Cancers Genitourinary

Age

People18+

Trial acronym

DARO-LIPID

Clinical summary

Summary

There is increasing evidence that abnormal lipid (fat) metabolism promotes the growth of prostate cancer cells. We have previously shown that abnormal patterns of blood-borne lipids (called ceramides) can identify a group of people with metastatic hormone resistant prostate cancer who are likely to be resistant to the usual hormone treatments: abiraterone and enzalutamide.

In the DARO-LIPID study, researchers will first identify which participants with metastatic hormone resistant prostate cancer have the high ceramide lipid signature through a blood test.

Participants who do not have this lipid signature will receive usual care by their oncologist Participants with this lipid signature who consent to the study will all receive darolutamide as standard of care.

Participants will be randomly split into two groups with one group also receiving the lipid drug called Opagnib to target the abnormal lipid changes and the second group receiving a placebo.

The study is designed to see if Opaganib can increase the number of people who respond to Darolutamide, and increase the time that they get benefit from the treatment. Researchers will also look at how the Opaganib is affecting lipid/fat metabolism in the body/tumour.

Potential participants who meet all of the inclusion criteria and none of the exclusion criteria listed will be presented with a pre-screening consent. If they consent to pre-screening, a sample will be collected for PCPro biomarker testing. If the pre-screening assessment shows that the trial is suitable for the participants who have undergone pre-screening, then they will be presented with the main study consent and will be given the opportunity to decide if they want to enrol in this trial or not.

Conditions

This trial is treating people with metastatic hormone resistant prostate cancer

Eligibility

Inclusion

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 o

Exclusion

 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

Inclusion

  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • You have had a certain type of treatment or surgical procedure.

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

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More information

Trial Identifiers

Information on this page is partially produced from ANZCTR *. View further details about this trial on the registry via the links below:

Trial sponsor

Australian and New Zealand Urogenital and Prostate Cancer Trials Group

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

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