Darolutamide vs Enzalutamide for Prostate Cancer

(ARACOG Trial)

Not currently recruiting at 10 trial locations

Overseen By Director Quality Management and Compliance

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Alliance Foundation Trials, LLC.

Must be taking: LHRH agonists

Disqualifiers: Non-adenocarcinoma, High testosterone, 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

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, darolutamide (Nubeqa) and enzalutamide (Xtandi), to assess their effects on thinking and memory in men with specific types of prostate cancer. Researchers aim to determine if these drugs impact cognitive function—such as memory and attention—differently. Participants should have prostate cancer that has either spread or not responded to hormone therapy and must be able to complete cognitive tests in English. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must continue taking a GnRH agonist or antagonist if you are medically castrated.

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

Research has shown that enzalutamide is generally well-tolerated. In studies involving thousands of patients, enzalutamide reduced the risk of death by 33% compared to those not receiving it, suggesting its effectiveness and safety for many patients. These studies found no unexpected safety issues. Common side effects include tiredness and high blood pressure, which can often be managed.

Specific safety details for darolutamide are not yet available, as this trial is in an early stage. Early trials typically focus on assessing safety, and treatments usually demonstrate some safety before reaching this stage.

Both treatments are being tested alongside standard prostate cancer treatments, aiding doctors in understanding their safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for prostate cancer, which often focus on hormone therapy or chemotherapy, Darolutamide and Enzalutamide offer unique approaches as androgen receptor inhibitors. Darolutamide stands out because it is designed to minimize the crossing of the blood-brain barrier, potentially reducing certain side effects like fatigue and cognitive issues commonly seen with other treatments. Enzalutamide is known for its potent action against androgen receptors, effectively slowing cancer progression with a once-daily oral dose. Researchers are excited about these treatments because they present promising options that may enhance quality of life and improve outcomes for patients with prostate cancer.

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

This trial will compare Darolutamide with Enzalutamide for treating prostate cancer. Research has shown that Enzalutamide effectively treats prostate cancer, helping patients live longer and preventing the cancer from worsening. Specifically, studies found that patients taking Enzalutamide had a better chance of living without their cancer progressing, with a 33% lower risk of death compared to other treatments. Meanwhile, early research suggests that Darolutamide might also be effective for prostate cancer. It blocks male hormones that help the cancer grow, potentially slowing the disease. However, more information is needed to confirm its effectiveness compared to Enzalutamide. ^{1 2 6 7 8}

Who Is on the Research Team?

Evanthia Galanis, MD

Principal Investigator

Alliance Foundation Trials

Are You a Good Fit for This Trial?

Men with advanced prostate cancer that's resistant to hormone therapy, either spread (metastatic) or not (non-metastatic). They must be able to swallow pills, have low testosterone from treatment, and be in fairly good health. Men who've had certain treatments like enzalutamide or darolutamide before, brain metastasis, seizures, dementia, or are at risk of falls can't join.

Inclusion Criteria

My prostate cancer is growing despite hormone therapy, with increasing PSA levels.

I can swallow pills without any issues.

My prostate cancer is confirmed and does not have neuroendocrine or small cell features.

Exclusion Criteria

I will undergo radiation treatment for more than 21 days during the study.

Use of investigational agents for the treatment of prostate cancer within 4 weeks of study entry

I had chemotherapy for prostate cancer more than 6 months ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either enzalutamide or darolutamide in combination with standard LHRH agonist based treatment

48 weeks

Regular visits for cognitive assessments and treatment monitoring

Crossover

Participants may cross over to the opposite treatment arm at 12 and 24 weeks if criteria are met

Up to 48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Darolutamide
• Enzalutamide

Trial Overview The study is testing the effects of two drugs on thinking skills in men with advanced prostate cancer. Half will take Darolutamide and half Enzalutamide along with standard hormone-blocking injections. Their cognitive functions will be measured using a special computerized test called CANTAB.

How Is the Trial Designed?

Group I: Darolutamide (DARO) Active Control 1 Intervention

Patients will take DARO at a dose of 600 mg (300 mg ×2 tablets) by mouth twice daily beginning on Day 1, of Week 1. Patients will take DARO throughout planned treatment period or withdrawal of consent or progression of disease requiring change in therapy.

Group II: Enzalutamide (ENZ) Active Control 1 Intervention

Patients will take ENZ at a dose of 160 mg PO once daily (QD), beginning on Day 1, of Week 1. Patients will take ENZ throughout planned treatment period or withdrawal of consent or progression of disease requiring change in therapy.

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?

Alliance Foundation Trials, LLC.

Lead Sponsor

Trials

25

Recruited

27,200+

Bayer

Industry 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, 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]

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 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 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]

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. pfizer.com pfizer.com/news/press-release/press-release-detail/astellas-and-pfizers-xtanditm-enzalutamide-shows-long-term

Astellas and Pfizer's XTANDI™ (enzalutamide) Shows ... OS at 96 months was 50% with XTANDI and 40% for NSAA; progression-free survival (PFS) also favored XTANDI over NSAA (HR: 0.49; 95% CI, 0.42-0.57) ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2510310?query=featured_home

Improved Survival with Enzalutamide in Biochemically ... In this trial, enzalutamide plus leuprolide led to significantly longer overall survival than leuprolide alone among patients with castration- ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40660075/

The efficacy and safety of enzalutamide in metastatic ... Results: The data of 2275 patients were analyzed eventually. Enzalutamide reduced the risk of death by 33% compared to the control. Specifically ...

4. targetedonc.com targetedonc.com/shorts/a-13-year-old-drug-s-persisting-power-in-prostate-cancer

A 13-Year-Old Drug's Persisting Power in Prostate Cancer Two-year OS rates were 80% vs 63%. The treatment also yielded a record 57.1% pathological pCR. ... Clinical Trial Achieves 60% Reduction in the Risk of Tumor ...

5. xtandihcp.com xtandihcp.com/cspc/efficacy

Efficacy CSPC | HCP Site | XTANDI® (enzalutamide) XTANDI (single agent) significantly improved metastasis-free survival vs placebo + GnRH therapy* · Number of events: 63 (17.7%) with XTANDI (single agent) vs 92 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12504157/

Comparative effectiveness and safety of enzalutamide ... Enzalutamide use was associated with superior overall survival (hazard ratio 0.88, 95% confidence interval [CI] 0.82–0.96) compared with ...

7. xtandi.com xtandi.com/clinical-trials

Clinical Trial Results | XTANDI® (enzalutamide) Men taking XTANDI had a 61% lower chance of their cancer progressing compared with men not taking XTANDI during the study. Progression was seen in 89 men (15.5 ...

8. pfizer.com pfizer.com/news/press-release/press-release-detail/xtandir-plus-leuprolide-reduced-risk-death-40-vs-leuprolide

XTANDI® Plus Leuprolide Reduced Risk of Death by 40% ... The probability of survival at 8 years was an unprecedented 78.9% with XTANDI plus leuprolide versus 69.5% with leuprolide, in men with ...