Darolutamide + ADT for Prostate Cancer

(ARANOTE Trial)

Not currently recruiting at 214 trial locations

Overseen By Bayer Clinical Trials Contact

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Bayer

Must be taking: Androgen deprivation therapy

Must not be taking: Second-gen AR inhibitors, Chemotherapy

Disqualifiers: Stroke, Myocardial infarction, Uncontrolled hypertension, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 36 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a drug called darolutamide when combined with standard hormone therapy (Androgen Deprivation Therapy, or ADT) for prostate cancer that has spread. The goal is to determine if this combination is more effective and safe compared to a placebo with ADT. It targets patients diagnosed with metastatic prostate cancer who began hormone therapy no more than 12 weeks ago. Participants must have good overall health and be able to take oral medication. As a Phase 3 trial, this study serves as the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those who have used certain prostate cancer treatments or high-dose corticosteroids recently. It's best to discuss your specific medications with the trial team.

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

Research has shown that darolutamide, when combined with androgen deprivation therapy (ADT), is generally safe. In previous studies, most side effects were mild, with common issues including rash, fatigue, hot flashes, and sweating. Only about 7.4% of patients experienced moderate side effects, such as more intense fatigue or rash, while serious side effects were rare.

Darolutamide has also been well tolerated over extended periods. Even with long-term use, patients did not encounter many serious health problems. This track record can help instill confidence in the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about darolutamide for prostate cancer because it offers a unique mechanism of action compared to current treatments. Unlike other therapies that primarily target androgen production, darolutamide acts as an androgen receptor inhibitor, blocking the effects of male hormones that fuel cancer growth. This dual approach, when combined with Androgen Deprivation Therapy (ADT), potentially enhances treatment effectiveness by attacking the cancer on two fronts. Additionally, darolutamide is designed to minimize some of the side effects associated with other androgen receptor inhibitors, making it a promising option for patients seeking effective and manageable treatment.

What evidence suggests that darolutamide + ADT might be an effective treatment for prostate cancer?

In this trial, participants will receive either a combination of darolutamide with androgen deprivation therapy (ADT) or a placebo with ADT. Research has shown that combining darolutamide with ADT can significantly improve outcomes for prostate cancer patients. Specifically, studies have found that this combination increases the time patients live without their cancer worsening by 40% compared to those taking a placebo. This allows patients to go longer without their cancer progressing. Additionally, darolutamide effectively lowers PSA levels, which are used to monitor prostate cancer. These findings strongly suggest that this treatment could be effective for prostate cancer that has spread and still responds to hormone therapy. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

Men with confirmed metastatic hormone-sensitive prostate cancer, who have started ADT within the last 12 weeks and are in good physical condition (ECOG PS of 0-2) can join. They must not have had certain heart conditions or other cancer treatments like chemotherapy for prostate cancer in the past 6 months.

Inclusion Criteria

I am able to care for myself and perform daily activities.

My bone marrow, liver, and kidneys are functioning well.

I started hormone therapy for cancer not more than 12 weeks ago.

Exclusion Criteria

I have not had radiotherapy in the last 2 weeks.

I cannot swallow pills.

I have not used specific hormone therapies, chemotherapy, or other treatments for prostate cancer recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive darolutamide or placebo in combination with androgen deprivation therapy (ADT)

36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 55 months

What Are the Treatments Tested in This Trial?

Interventions

• Androgen Deprivation Therapy (ADT)
• Darolutamide

Trial Overview The trial is testing if adding Darolutamide to standard ADT improves outcomes for men with metastatic hormone-sensitive prostate cancer compared to ADT alone. Participants will either receive Darolutamide or a placebo alongside their regular ADT treatment.

How Is the Trial Designed?

Group I: Darolutamide+ADT Experimental Treatment 2 Interventions

Participants will receive darolutamide 600 mg (2 tablets of 300 mg) twice daily with food and ADT of investigator's choice as standard therapy

Group II: Placebo+ADT Placebo Group 2 Interventions

Participants will receive placebo twice daily with food and ADT of investigator's choice as standard therapy

Androgen Deprivation Therapy (ADT) is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Androgen Deprivation Therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Non-metastatic high-risk prostate cancer

Approved in United States as Androgen Deprivation Therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Non-metastatic high-risk prostate cancer

Approved in Canada as Androgen Deprivation Therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Non-metastatic high-risk prostate cancer

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

Orion Corporation, Orion Pharma

Industry Sponsor

Trials

140

Recruited

45,200+

Liisa Hurme

Orion Corporation, Orion Pharma

Chief Executive Officer since 2022

PhD in Biochemistry, University of Helsinki

Hilpi Rautelin

Orion Corporation, Orion Pharma

Chief Medical Officer since 2023

MD, University of Turku

Published Research Related to This Trial

Darolutamide is an FDA-approved nonsteroidal androgen inhibitor specifically for treating castration-resistant non-metastatic prostate cancer, providing a new option for patients whose PSA levels are rising despite low testosterone.

When used alongside androgen deprivation therapy (ADT), darolutamide, like other newer agents in its class, has been shown to prolong metastasis-free survival and median survival, making it an effective treatment choice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using darolutamide in advanced prostate cancer: How I Do It. Hamilton, J.[2021]

In a phase 3 trial with 1306 patients suffering from metastatic, hormone-sensitive prostate cancer, the addition of darolutamide to standard treatment significantly reduced the risk of death by 32.5% compared to placebo, indicating its efficacy in improving overall survival.

The safety profile of darolutamide was comparable to placebo, with similar rates of adverse events, suggesting that it can be safely combined with androgen-deprivation therapy and docetaxel without increasing the risk of severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. Smith, MR., Hussain, M., Saad, F., et al.[2023]

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]

Darolutamide is a new nonsteroidal androgen receptor inhibitor approved for treating nonmetastatic castration-resistant prostate cancer (nmCRPC), showing promise as a second-generation antiandrogen.

The drug received FDA approval in July 2019 and is currently undergoing further evaluation in the E.U., highlighting its potential as a significant treatment option for men with nmCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide for treatment of castration-resistant prostate cancer. Rhea, LP., Mendez-Marti, S., Aragon-Ching, JB.[2020]

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 novel nonsteroidal androgen receptor antagonist, has shown a favorable safety profile and significant antitumor activity in early trials for patients with metastatic castration-resistant prostate cancer (CRPC).

Ongoing phase III trials, such as ARAMIS and ARASENS, are evaluating darolutamide's effectiveness in improving metastasis-free survival and overall survival when combined with standard androgen deprivation therapy and docetaxel in men with high-risk nonmetastatic and metastatic hormone-sensitive prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Development of Darolutamide: A Novel Androgen Receptor Antagonist for the Treatment of Prostate Cancer. Fizazi, K., Smith, MR., Tombal, B.[2019]

Citations

1. 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 ...

2. 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 ...

3. 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 ...

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

Real world outcomes of darolutamide efficacy and safety in ... Adverse events led to dose reductions in 4.5% (n=6) of nmHSPC and 1.8% (n=1) of mHSPC patients. Surgical data for 51.1% (n=68) of nmHSPC ...

5. nubeqahcp.com nubeqahcp.com/efficacy/mcspc

mCSPC Efficacy | NUBEQA® (darolutamide) | HCP At the data cutoff date for the primary analysis (June 7, 2024), the median treatment duration was 24.2 months in the NUBEQA group compared with 17.3 months in ...

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. nature.com nature.com/articles/s41391-025-01047-7

DARolutamide ObservationaL (DAROL) study in patients ... Darolutamide showed consistent safety and effectiveness in DAROL vs ARAMIS. Most treatment-emergent adverse events were grade 1/2. Two-year ...

8. 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 ...