Early phase clinical trial of riboclibib for prostate cancer
Ressearch impact: The Centre is leading an early-phase clinical trial of the cyclin dependent kinase inhibitor, ribociclib, for prostate cancer following our prior research showing promising anti-tumour effects in a patient-derived explant (PDE) model.
Our previous research and rationale
The cyclin/cyclin-dependent kinase/retinoblastoma (CDK4/6) pathway is critical for cell replication and inhibition of this pathway may have a role in controlling some human cancers where this pathway is amplified. Using the human prostate cancer explant model developed by Centre researchers, we previously reported in a landmark publication, that inhibiting CDK4/6 impaired the capacity of prostate cancer cells in human prostate tumours to proliferate. These CDK4/6 inhibitors are already being used to treat women with breast cancer.
Aim
In collaboration with medical oncologist Prof Lisa Horvath from the Chris O’Brien Lifehouse in NSW, we are now testing the safety and potential effect of ribociclib in an early phase clinical trial in men undergoing surgery for high risk, localised prostate cancer. The trial is funded by Cancer Australia.
Our study
Prior to surgical removal of the prostate men are receiving 400mg of oral ribociclib daily for 21 days. Biopsies of the prostate cancer prior to treatment and then at the time of surgical removal of the prostate, are being taken to measure markers of prostate cancer cell proliferation. Men are being evaluated for safety signals to ensure the drug is safe to proceed to larger studies.
In parallel, our research is investigating what biological markers can be used to measure the drug response to support future clinical trials. Further information about the study may be found at
More information about this clinical trial may be found at:
ANZ Clinical Trials Register Study ID: ACTRN12618000354280 (NSW Study)
Contact: Professor Lisa Butler
FCMHW@The University of Adelaide & South Australian Health & Medical Research Institute
References from the Centre
Scheinberg T et al. Pharmacodynamics effects of CDK4/6 inhibitor LEE011 (ribociclib) in high-risk, localised prostate cancer: a study protocol for a randomised controlled phase II trial (LEEP study: LEE011 in high-risk, localised Prostate cancer). BMJ Open. 2020 Jan 26;10(1):e033667. doi: 10.1136/bmjopen-2019-033667. PMID: 31988233.
Comstock CE et al. Targeting cell cycle and hormone receptor pathways in cancer. Oncogene. 2013 Nov 28;32(48):5481-91. doi: 10.1038/onc.2013.83. Epub 2013 May 27. PMID: 23708653