Darolutamide vs Enzalutamide for Prostate Cancer

(ARACOG Trial)

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

111 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a prospective, randomized, open-label phase II study comparing cognitive outcomes between men with metastatic and non-metastatic castration resistant prostate cancer (CRPC) or metastatic hormone sensitive prostate cancer (HSPC). Approximately 132 patients will be enrolled. Eligible patients will be randomized in a 1:1 fashion to treatment with enzalutamide 160 mg orally daily or darolutamide 600 mg orally twice daily, in combination with standard LHRH agonist based treatment. Cognitive assessments will be performed using modules from Cambridge Neuropsychological Test Automated Battery (CANTAB) an internationally recognized software for assessing cognitive function and impairment.

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.

What data supports the effectiveness of the drug Darolutamide for prostate cancer?

Darolutamide has been shown to be effective in treating prostate cancer, particularly in men with non-metastatic castration-resistant prostate cancer, by significantly prolonging the time patients live without the cancer spreading. It has also been effective in combination with other treatments for metastatic hormone-sensitive prostate cancer, improving overall survival rates. ^{1 2 3 4 5}

Is Darolutamide safe for humans?

Darolutamide is generally well tolerated and has a manageable safety profile, with fewer central nervous system-related side effects compared to other similar drugs. It does not cross the blood-brain barrier, reducing the risk of seizures, and has been well tolerated in clinical trials for prostate cancer. ^{1 2 3 6 7}

How does the drug darolutamide differ from other treatments for prostate cancer?

Darolutamide is unique because it is a non-steroidal androgen receptor inhibitor with a distinct chemical structure, which may make it effective for patients who are resistant to other similar drugs like enzalutamide. It also has minimal penetration into the brain, potentially reducing certain side effects compared to other treatments. ^{1 2 3 4 8}

Research Team

Evanthia Galanis, MD

Principal Investigator

Alliance Foundation Trials

Eligibility Criteria

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.

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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]

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, 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 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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Darolutamide: First Approval. [2020]

2. France pubmed.ncbi.nlm.nih.gov

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

3. France pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

Sequential therapy with darolutamide in patients with non-metastatic castration-resistant prostate cancer resistant to enzalutamide or apalutamide. [2023]

5. Germany 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. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Indirect Comparison of Darolutamide versus Apalutamide and Enzalutamide for Nonmetastatic Castration-Resistant Prostate Cancer. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Darolutamide as a Second-Generation Androgen Receptor Inhibitor in the Treatment of Prostate Cancer. [2021]

8. England pubmed.ncbi.nlm.nih.gov

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