Darolutamide vs Enzalutamide for Prostate Cancer
(ARAMON Trial)
Recruiting in Palo Alto (17 mi)
+4 other locations
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: Bayer
No Placebo Group
Prior Safety Data
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.
12345What 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.
12367Is 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.
12348Eligibility 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
My prostate cancer diagnosis was confirmed through lab tests.
I am a man aged 18 or older.
More than 30 days (or 5 half-lives) (whichever is longer) since prior participation in another clinical trial with an investigational medicinal product
+7 more
Exclusion Criteria
I have not had radiation or major surgery in the last 4 weeks.
I had hormone therapy for prostate cancer, but not in the last 6 months.
My blood pressure is not well-controlled.
+7 more
Participant Groups
The ARAMON study is testing how Darolutamide affects testosterone levels compared to Enzalutamide in men with recurring prostate cancer not treated hormonally before. Initially, all take Darolutamide; based on results, they may later be randomly assigned to continue it or switch to Enzalutamide.
3Treatment groups
Experimental Treatment
Active Control
Group I: Randomized phase: Darolutamide treatmentExperimental Treatment1 Intervention
The conduct of the randomized phase is dependent on the results of the lead-in phase.
Group II: Lead-in phase: Darolutamide treatmentExperimental Treatment1 Intervention
Darolutamide treatment arm is single cohort in lead-in phase.
Group III: Randomized phase: Enzalutamide treatmentActive Control1 Intervention
The conduct of the randomized phase is dependent on the results of the lead-in phase.
Darolutamide is already approved in United States, European Union, Canada, Australia for the following indications:
🇺🇸 Approved in United States as Nubeqa for:
- Non-metastatic castration-resistant prostate cancer (nmCRPC)
- Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel
🇪🇺 Approved in European Union as Nubeqa for:
- Non-metastatic castration-resistant prostate cancer (nmCRPC)
- Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel
🇨🇦 Approved in Canada as Nubeqa for:
- Non-metastatic castration-resistant prostate cancer (nmCRPC)
- Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel
🇦🇺 Approved in Australia as Nubeqa for:
- Non-metastatic castration-resistant prostate cancer (nmCRPC)
- Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Genesis Research LLCSherman Oaks, CA
Beth Israel Deaconess Medical Center - BostonBoston, MA
Memorial Sloan Kettering Cancer CenterNew York, NY
Central Ohio Urology GroupColumbus, OH
More Trial Locations
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Who Is Running the Clinical Trial?
BayerLead Sponsor
References
Darolutamide: First Approval. [2020]Darolutamide (NUBEQA™) is a structurally distinct non-steroidal androgen receptor antagonist being developed by Orion and Bayer as a treatment for prostate cancer. Based on positive results in the phase III ARAMIS trial, darolutamide was recently approved in the USA for the treatment of men with non-metastatic castration-resistant prostate cancer. This article summarizes the milestones in the development of darolutamide leading to this first approval.
Darolutamide: A Review in Metastatic Hormone-Sensitive Prostate Cancer. [2023]Darolutamide (NUBEQA®) is an oral androgen receptor inhibitor (ARi) that is approved for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy (ADT) and docetaxel. In a pivotal trial, darolutamide plus ADT and docetaxel was superior to placebo plus ADT and docetaxel in prolonging the primary endpoint of overall survival, with improvements also reported in most secondary endpoints. Treatment with darolutamide plus ADT and docetaxel was associated with a manageable tolerability profile. Furthermore, the adverse events reported with darolutamide plus ADT and docetaxel were generally consistent with the safety profiles previously reported for ADT and docetaxel. Darolutamide expands the availability of treatment options in mHSPC and may be useful as a treatment for high-volume disease (typically defined as ≥ 4 bone metastases with spread outside of the pelvis and vertebral column).
Darolutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. [2022]Oral darolutamide (Nubeqa™) is a novel second-generation, nonsteroidal, selective androgen receptor (AR) inhibitor indicated for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). In the pivotal multinational, phase 3 ARAMIS trial in men with nmCRPC, relative to placebo plus ongoing androgen deprivation therapy (ADT), darolutamide (+ ADT) significantly prolonged metastasis-free survival (MFS) at the time of the primary analysis and overall survival (OS) at the time of the final OS analysis and was generally well tolerated in extended follow-up. Albeit long-term data from the real-world setting are required to fully define the safety profile of darolutamide, current evidence from the final ARAMIS analysis indicates that darolutamide has a low propensity for CNS-related adverse events (AEs) associated with other currently approved second-generation AR inhibitors. Given the efficacy and safety evidence from the final ARAMIS analysis and the key role of second-generation AR inhibitors in the management of nmCRPC, darolutamide + ADT represents an important emerging option for the treatment of men with nmCRPC who are at high risk of developing metastatic prostate cancer.
Sequential therapy with darolutamide in patients with non-metastatic castration-resistant prostate cancer resistant to enzalutamide or apalutamide. [2023]Enzalutamide, apalutamide, and darolutamide are currently recommended for patients with non-metastatic castration-resistant prostate cancer (nmCRPC), but cross-resistance of androgen receptor-axis-targeted therapies (ARAT) occurs. Because darolutamide has a distinct chemical structure to other non-steroidal antiandrogens, it may be effective for nmCRPC patients resistant to enzalutamide or apalutamide. We retrospectively evaluated the efficacy of switching to darolutamide in patients with nmCRPC. We included nine nmCRPC patients who experienced biochemical progression on enzalutamide or apalutamide and were switched over to darolutamide. Five patients (55.5%) had a PSA response >50% decline after starting darolutamide, with an average of 73% PSA decline. Median progression-free survival was 6 months. In conclusion, an ARAT switch from enzalutamide or apalutamide to darolutamide might be effective for nmCRPC. Although the validation in a large-scale cohort is necessary, the switch to darolutamide could be a promising therapeutic option after the progression of 1st line ARAT in nmCRPC patients.
Phase 1 study of darolutamide (ODM-201): a new-generation androgen receptor antagonist, in Japanese patients with metastatic castration-resistant prostate cancer. [2023]This trial assessed the safety, pharmacokinetics, and efficacy of darolutamide (ODM-201), a new-generation nonsteroidal androgen receptor antagonist, in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC).
Indirect Comparison of Darolutamide versus Apalutamide and Enzalutamide for Nonmetastatic Castration-Resistant Prostate Cancer. [2021]No published head-to-head randomized trials have compared the safety and efficacy of darolutamide vs apalutamide or enzalutamide in nonmetastatic castration-resistant prostate cancer. This study compares prespecified adverse events and metastasis-free survival associated with darolutamide vs apalutamide, and darolutamide vs enzalutamide, via matching-adjusted indirect comparisons.
Darolutamide as a Second-Generation Androgen Receptor Inhibitor in the Treatment of Prostate Cancer. [2021]Prostate cancer (PC) is known as the most frequent cancer among men in the world. Androgen Deprivation Therapy (ADT) is one of the initial treatment approaches in the PC therapy and various drugs can be used in routine Hormonal therapy for PC therapy. Nevertheless, PC cells can survive and continue their growth via different mechanisms which lead to their resistance to common treatments i.e., Enzalutamide. olutamide (ODM-201) is a second-generation androgen receptor (AR) inhibitor with a new chemical structure and has a high affinity to the AR. Darolutamide does not cross the blood-brain barrier and for this reason, reduces the possibility of seizures. Darolutamide can also inhibit the transcriptional activity of several AR mutant variants (F877L, F877L/T878A, and H875Y/T878A), which are Enzalutamide resistant. In this review, we reviewed the results of different studies: in vitro, animal model and phase 1, 2 and 3 clinical trials (ARADES, ARAFOR and ARAMIS). We shall discuss worldwide phase 2 and 3 clinical trials (ARASENS and ODENZA) that are in progress, in order to demonstrate the advantages of Darolutamide consumption in different groups of patients. Darolutamide has shown high potential in inhibiting the growth of MR49F (Enzalutamide resistant PC cells) and VCaP (Castration-resistant PC cells) cell lines and transcriptional activities of AR. Fewer doses of Darolutamide are needed compared to Enzalutamide. The drug had significant anti-tumor activity and no effect on serum testosterone levels in animal models. Darolutamide demonstrates its safety and efficacy in different studies and was well tolerated nearly in all of the patients.
Darolutamide (ODM-201) for the treatment of prostate cancer. [2018]Androgen deprivation therapy (ADT) is a mainstay initial treatment for advanced hormone-sensitive prostate cancer (HSPC), but disease progression to castration-resistant prostate cancer (CRPC) invariably occurs when patients do not succumb to another disease or comorbidity. Recognition that the androgen receptor (AR) axis continues to drive disease progression has led to the development of several AR-directed approved agents, including abiraterone acetate and enzalutamide. An investigational agent, darolutamide (ODM-201, BAY-1841788), has completed early-phase clinical trials, and two global phase III trials are currently accruing patients. Areas covered: The unmet clinical need, pharmacokinetics, preclinical development, and clinical efficacy and safety of darolutamide for the treatment of advanced prostate cancer are reviewed. The design of two ongoing phase III trials (ARAMIS and ARASENS) of darolutamide in men with non-metastatic CRPC and metastatic HSPC, respectively, are also discussed. Expert opinion: Darolutamide is an oral, investigational, high-affinity AR antagonist which has activity against known AR mutants that confer resistance to other second-generation antiandrogens, has minimal blood-brain barrier penetration, and does not significantly increase serum testosterone. These features may offer potential advantages over the second-generation antiandrogens. In the phase I/II ARADES trial, darolutamide demonstrated promising antitumor activity and a favorable safety profile in men with metastatic CRPC.