Darolutamide vs Enzalutamide for Prostate Cancer

(ARAMON Trial)

No longer recruiting at 10 trial locations

Overseen By Bayer Clinical Trials Contact

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Bayer

Must not be taking: Glucocorticoids, AR inhibitors

Disqualifiers: Stroke, Myocardial infarction, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find a better treatment for men with hormone-naïve prostate cancer that has returned after initial treatment, indicated by rising PSA levels (a protein marker for prostate cancer). Researchers are comparing two drugs, Darolutamide (Nubeqa) and Enzalutamide (Xtandi), to determine which manages this condition more effectively with fewer side effects. The trial begins with all participants taking Darolutamide and may expand to include Enzalutamide based on results. Men who have undergone surgery or radiation for prostate cancer and now experience rising PSA levels, but no symptoms, might be suitable candidates. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that Darolutamide is well tolerated by patients. Common side effects include mild rash, tiredness, and hot flashes, with only 7.4% of patients experiencing moderate side effects. Importantly, only 0.5% faced more serious issues, suggesting that Darolutamide is relatively safe for most people.

For Enzalutamide, studies have reported specific side effects due to its potential impact on the brain. This can lead to increased testosterone levels, causing side effects like breast tenderness and enlargement in men. However, overall survival rates for patients on Enzalutamide remain high, indicating that many handle the treatment well despite these side effects.

Both treatments have approval for other types of prostate cancer, adding a layer of safety confidence. However, individual responses can vary, so monitoring for any side effects during treatment is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments, darolutamide and enzalutamide, because they offer promising options for prostate cancer. Unlike traditional treatments like surgery, radiation, or chemotherapy, both drugs target specific pathways within cancer cells, potentially reducing side effects. Darolutamide, in particular, is noted for its ability to block androgen receptors without crossing the blood-brain barrier, which may lead to fewer cognitive side effects compared to other drugs. Enzalutamide, an established treatment, is recognized for effectively inhibiting androgen receptors but may have more pronounced side effects. These unique features have researchers hopeful that darolutamide could offer a more tolerable alternative for patients with prostate cancer.

What evidence suggests that this trial's treatments could be effective for hormone-naïve prostate cancer?

This trial will compare Darolutamide and Enzalutamide for treating prostate cancer. Research shows that both drugs effectively treat prostate cancer by blocking male hormones that promote cancer growth. Participants may receive Darolutamide, which, when combined with standard hormone therapy, can extend the time patients live without their cancer worsening by 40%. Others may receive Enzalutamide, which also shows positive results, helping patients with recurring prostate cancer live longer. However, Enzalutamide can cause side effects because it enters the brain, potentially increasing testosterone levels and leading to breast changes in men. Darolutamide is less likely to cause these side effects because it doesn't enter the brain as much. Both treatments are well-regarded by doctors for their effectiveness against prostate cancer. ^{3 4 5 6 7}

Are You a Good Fit for This Trial?

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.

More than 30 days (or 5 half-lives) (whichever is longer) since prior participation in another clinical trial with an investigational medicinal product

Serum testosterone >150 ng/dl

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-in Phase

Participants take Darolutamide by mouth twice a day. Testosterone levels are monitored and measured at 12, 24, and 52 weeks.

52 weeks

Regular visits for monitoring and assessments

Randomized Phase

Participants are randomly assigned to receive either Darolutamide or Enzalutamide. Treatment duration is between 12 to 52 weeks.

12-52 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse event tracking up to 30 days after the last dose.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Darolutamide
• Enzalutamide

Trial Overview 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.

How Is the Trial Designed?

Group I: Randomized phase: Darolutamide treatment Experimental Treatment 1 Intervention

The conduct of the randomized phase is dependent on the results of the lead-in phase.

Group II: Lead-in phase: Darolutamide treatment Experimental Treatment 1 Intervention

Darolutamide treatment arm is single cohort in lead-in phase.

Group III: Randomized phase: Enzalutamide treatment Active Control 1 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 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

Who Is Running the Clinical Trial?

Bayer

Lead Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

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

Published Research Related to This Trial

Darolutamide, an oral androgen receptor inhibitor, significantly improves overall survival in patients with metastatic hormone-sensitive prostate cancer when combined with androgen deprivation therapy and docetaxel, compared to placebo.

The treatment with darolutamide has a manageable safety profile, with adverse events aligning with those typically seen in androgen deprivation therapy and docetaxel, making it a viable option for patients with high-volume disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide: A Review in Metastatic Hormone-Sensitive Prostate Cancer. Lee, A.[2023]

Darolutamide (NUBEQA™) is a new non-steroidal androgen receptor antagonist approved for treating non-metastatic castration-resistant prostate cancer in men, based on positive results from the phase III ARAMIS trial.

The approval of darolutamide marks a significant milestone in prostate cancer treatment, highlighting its efficacy and safety profile as demonstrated in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide: First Approval. Markham, A., Duggan, S.[2020]

Darolutamide is an investigational oral medication that acts as a high-affinity androgen receptor antagonist, showing promising antitumor activity and a favorable safety profile in early-phase trials for advanced prostate cancer.

Unlike other antiandrogens, darolutamide has minimal penetration of the blood-brain barrier and does not significantly increase serum testosterone levels, which may provide advantages in treating patients with resistance to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide (ODM-201) for the treatment of prostate cancer. Shore, ND.[2018]

Darolutamide, a new androgen receptor antagonist, was found to be well tolerated in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC), with most treatment-emergent adverse events being mild (Grade 1/2).

The pharmacokinetics of darolutamide showed a dose-dependent increase in drug levels, and while only 11% of patients showed a prostate-specific antigen response, the drug did not present any new safety concerns compared to Western populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of darolutamide (ODM-201): a new-generation androgen receptor antagonist, in Japanese patients with metastatic castration-resistant prostate cancer. Matsubara, N., Mukai, H., Hosono, A., et al.[2023]

In the phase 3 ARAMIS trial, darolutamide significantly improved metastasis-free survival and overall survival in men with non-metastatic castration-resistant prostate cancer compared to placebo, indicating its efficacy when combined with ongoing androgen deprivation therapy.

Darolutamide was generally well tolerated, showing a low risk of central nervous system-related side effects, which is a common concern with other second-generation androgen receptor inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. Scott, LJ.[2022]

In a study of 9 patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who progressed on enzalutamide or apalutamide, switching to darolutamide resulted in a significant PSA response, with 55.5% of patients showing over a 50% decline in PSA levels.

The median progression-free survival after switching to darolutamide was 6 months, suggesting that darolutamide may be an effective treatment option for patients who have developed resistance to other androgen receptor-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential therapy with darolutamide in patients with non-metastatic castration-resistant prostate cancer resistant to enzalutamide or apalutamide. Fujmoto, S., Fujita, K., Nishimoto, M., et al.[2023]

Darolutamide is a promising second-generation androgen receptor inhibitor that effectively targets Enzalutamide-resistant prostate cancer cells, showing significant anti-tumor activity in various studies, including in vitro and clinical trials.

Unlike Enzalutamide, Darolutamide does not cross the blood-brain barrier, which reduces the risk of seizures, and it has been well tolerated by patients, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide as a Second-Generation Androgen Receptor Inhibitor in the Treatment of Prostate Cancer. Abbasi, A., Movahedpour, A., Amiri, A., et al.[2021]

In a comparison of darolutamide with apalutamide and enzalutamide for treating nonmetastatic castration-resistant prostate cancer, no differences in metastasis-free survival were found, indicating similar efficacy among the treatments.

Darolutamide demonstrated a better safety profile, with significantly lower rates of falls, fractures, and rashes compared to apalutamide, and lower rates of dizziness and fatigue compared to enzalutamide, suggesting it may be a preferable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indirect Comparison of Darolutamide versus Apalutamide and Enzalutamide for Nonmetastatic Castration-Resistant Prostate Cancer. Halabi, S., Jiang, S., Terasawa, E., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40310703/

Real-world effectiveness of darolutamide in metastatic ... Darolutamide suppressed serum PSA levels by >50% in 5/44 M1-CRPC patients (11.4%), all previously 2GARA-naïve. M1-CRPC patients resistant only ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e17108

Real world outcomes of darolutamide efficacy and safety in ... Common side effects included rash, fatigue, hot flushes, and sweating, with 7.4% (n=14) experiencing grade 2 adverse events and 0.5% (n=1) with ...

3. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-metastatic-castration-sensitive-prostate-cancer

FDA approves darolutamide for metastatic castration ... Treatment with darolutamide resulted in a statistically significant improvement in rPFS compared to placebo. Median rPFS was not reached in the ...

4. bayer.com bayer.com/en/us/news-stories/new-data-for-nubeqa

New Data for NUBEQA® Build on Safety and Efficacy ... NUBEQA (darolutamide) plus androgen deprivation therapy (ADT) improved radiological progression-free survival (rPFS) by 40% (HR 0.60; 95% CI: 0.44-0.80) and 70 ...

5. nubeqa-us.com nubeqa-us.com/about-nubeqa/mcspc-study-results

Clinical Study | NUBEQA® (darolutamide) | Patient Website At the time of analysis, 29% (128 out of 446) of men taking NUBEQA + ADT had cancer worsening via scans or were no longer living compared to 42% (94 out of 223) ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37660438/

Efficacy and safety outcomes of darolutamide in patients ... Darolutamide significantly improved median metastasis-free survival by nearly 2 years and reduced the risk of death by 31% versus placebo, with a favourable ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28753851/

Safety and Antitumour Activity of ODM-201 (BAY-1841788) ... Patient summary: Prolonged treatment with high doses of ODM-201 was well tolerated and provided long-lasting disease control in patients with mCRPC. ODM-201 ...