Darolutamide vs Enzalutamide for Prostate Cancer
(ARAMON Trial)
Trial Summary
What is the purpose of this trial?
Researchers are looking for a better way to treat men who have biochemically recurrent hormone-naïve prostate cancer. Hormone-naïve prostate cancer is a prostate cancer that has not yet been treated with hormonal therapy including androgen deprivation therapy (ADT). Biochemically recurrence (BCR) means that patients who received local treatment (surgery or radiation therapy) for prostate cancer now present with a rise in the blood level of a specific protein called PSA (prostate-specific antigen) but no detectable cancer or cancer spreading after a treatment that aimed to cure their prostate cancer (e.g. surgery and radiation). This may mean that the cancer has come back as the PSA level can be taken as a marker for prostate cancer development. Although men with BCR may not have symptoms for many years, proper treatment for BCR is important as the cancer may spread to other parts of the body in 7-8 years. In prostate cancer patients, male sex hormones like testosterone (also called androgens) can sometimes help the cancer spread and grow. To reduce androgen levels in these patients, androgen deprivation therapy (ADT) is often used. Second generation androgen receptor inhibitors including Darolutamide and Enzalutamide are available for the treatment of prostate cancer in addition to ADT. These inhibitors work by blocking androgen receptors and preventing it from attaching to proteins in cancer cells in the prostate. It is already known that men with prostate cancer benefit from these treatments. But besides benefits, Darolutamide and Enzalutamide are not without side effects. Clinical studies have shown that treatment with Enzalutamide increase testosterone level in serum, probably because it can pass blood brain barrier and goes into the central nervous system (CNS). The increased testosterone levels are thought to cause some specific side effects including so called feminizing side effects like overdevelopment of the breast tissue in men, and breast tenderness. Darolutamide has a distinct chemical structure and reduced ability to enter the CNS compared with Enzalutamide. That means that Darolutamide potentially leads to fewer and less severe side effects than Enzalutamide. In this study researchers will collect more data to learn to what extent Darolutamide affects serum testosterone levels in men with BCR in hormone-naïve prostate cancer. This study will consist of 2 stages. In stage 1 (also called lead-in phase) all participants will take Darolutamide by mouth twice a day. The study team will monitor and measure testosterone levels in the blood after: * 12 weeks * 24 weeks and * 52 weeks of treatment. The second stage (also called randomized phase) is conditional and depends on the results from the stage 1. It will be conducted if after 24 weeks of treatment with Darolutamide in stage 1: * a mean change in blood testosterone levels is below 45% and * if the feminizing side effects (including overdevelopment of the breast tissue in men, and breast tenderness) will occur less frequently than previously reported. In the second stage of this study all participants will be randomly (by chance) assigned into two treatment groups, taking either Darolutamide twice daily or Enzalutamide once daily by mouth for a minimum of 12 and a maximum of 52 weeks. During both stages of this study the study team will: * do physical examinations * take blood and urine samples * examine heart health using ECG * examine heart and lung health using CPET * check bone density using x-ray scan (DEXA) * check vital signs * check if the participants' cancer has grown and/or spread using CT (computed tomography) or MRI (magnetic resonance imaging) and, if needed, bone scan * ask the participants questions about how they are feeling and what adverse events they are having. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments. The study participants who receive Darolutamide in stage 2 can continue to receive their treatments as long as they benefit from the treatment. The participants from the Enzalutamide group can also switch to treatment with Darolutamide after finishing stage 2. The study team will continue to check the participants' health and collect information about medical problems that might be related to Darolutamide until up to 30 days of last dose for those participants who continue on treatment with Darolutamide.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use systemic glucocorticoids, certain herbal products, or have had recent radiation therapy or major surgery. It's best to discuss your specific medications with the study team.
What data supports the idea that Darolutamide vs Enzalutamide for Prostate Cancer is an effective drug?
The available research shows that Darolutamide is effective for treating prostate cancer. In a major trial, Darolutamide combined with other treatments helped patients live longer compared to those who didn't receive it. It also showed good results in patients who didn't respond well to Enzalutamide, with over half of them experiencing a significant drop in PSA levels, which is a marker used to track prostate cancer. This suggests that Darolutamide can be a promising option, especially for those who have not had success with other treatments.12345
What safety data exists for Darolutamide and Enzalutamide in prostate cancer treatment?
Darolutamide has been shown to be generally well tolerated with a low propensity for CNS-related adverse events, as indicated by the ARAMIS trial. It has a manageable tolerability profile when used with ADT and docetaxel in metastatic hormone-sensitive prostate cancer. Darolutamide does not cross the blood-brain barrier, reducing the risk of seizures. Enzalutamide, on the other hand, is known to have CNS-related side effects. No direct head-to-head trials have compared the safety of Darolutamide and Enzalutamide, but indirect comparisons have been made.12367
Is the drug Darolutamide a promising treatment for prostate cancer compared to Enzalutamide?
Yes, Darolutamide is a promising drug for prostate cancer. It has shown to improve survival rates in patients with metastatic hormone-sensitive prostate cancer and non-metastatic castration-resistant prostate cancer. It is effective even for patients who did not respond well to Enzalutamide, making it a valuable option for treating prostate cancer.12348
Eligibility Criteria
Men over 18 with hormone-naïve prostate cancer that's come back after surgery or radiation, shown by rising PSA levels without visible spreading. They must have good organ function and no more than five non-painful metastatic lesions. No recent major surgeries or certain past treatments like ADT in the last six months are allowed.Inclusion Criteria
Exclusion Criteria
Treatment Details
Interventions
- Darolutamide
- Enzalutamide
Darolutamide is already approved in United States, European Union, Canada for the following indications:
- Non-metastatic castration-resistant prostate cancer (nmCRPC)
- Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel
- Non-metastatic castration-resistant prostate cancer (nmCRPC)
- Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel
- Non-metastatic castration-resistant prostate cancer (nmCRPC)
- Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel
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Who Is Running the Clinical Trial?
Bayer
Lead Sponsor
Bill Anderson
Bayer
Chief Executive Officer since 2023
BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT
Michael Devoy
Bayer
Chief Medical Officer since 2014
MD, PhD