Named PROpel (NCT03732820), the trial was recently presented at the 2019 Genitourinary Cancers Symposium, in San Francisco, in a poster titled “PROPEL: A randomized, phase III trial evaluating the efficacy and safety of olaparib combined with abiraterone as first-line therapy in patients with metastatic castration-resistant prostate cancer (mCRPC).”
Lynparza, jointly developed by AstraZeneca and Merck (MSD outside North America), is a treatment approved for some breast and ovarian cancers, and targets PARP proteins. By inhibiting these proteins, Lynparza (called olaparib, when used off-label) prevents cancer cells from repairing DNA errors, which eventually causes them to die.
In a prior Phase 2 trial, a combination of olaparib plus the standard treatment of Zytiga and prednisone, given as second-line treatment, significantly delayed disease progression or death among mCRPC patients who had previously received Taxotere (docetaxel).
While olaparib is particularly effective in cancers with mutations in DNA-repairing genes, such as BRCA1 and BRCA2, the combination benefited patients irrespective of their mutation status, suggesting that it could be used in a broader population of prostate cancer patients.
Thus, AstraZeneca and Merck designed PROpel to determine if olaparib could be added to Zytiga for the first-line treatment of mCRPC patients, regardless of mutations in DNA repair genes.
The trial, aiming to include 720 participants, will be conducted in approximately 200 locations across the U.S., Europe, Australia, Brazil, Canada, China, Korea, Spain, Chile, and Japan. To be eligible, patients must have not received any prior chemotherapy or new hormonal agents for their metastatic castration-resistant disease, but may have received Taxotere at the metastatic hormone-sensitive stage.
PROpel’s participants will be divided according to the site of metastasis — bone only, visceral, or other — and whether or not they previously received Taxotere. Then they will be randomly assigned to take Zytiga once daily and prednisone or prednisolone twice a day, plus either olaparib or a placebo twice daily.
The trial’s main goal is to determine if patients live longer without disease progression — assessed with radiological imaging scans — when olaparib is added to their treatment regimen. Secondary measures include time to another treatment or death, time to pain progression, overall survival, and health-related quality of life. The combination’s safety and tolerability will also be assessed.
Finally, researchers will confirm that the treatment is indeed effective regardless of mutations in DNA repair genes.
PROpel began enrolling participants in October 2018. For more information on study sites and how to enroll, click here.
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