Darolutamide + ADT for Prostate Cancer

(ARASTEP Trial)

Not currently recruiting at 461 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 generation ARIs, CYP 17 inhibitors

Disqualifiers: Small cell carcinoma, Brain metastasis, 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: 2

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining darolutamide with ADT (a treatment that lowers male hormones) can better control prostate cancer in men with rising PSA levels, indicating potential cancer recurrence. The goal is to determine if this combination helps patients live longer without cancer progression compared to ADT with a placebo (a non-active treatment). Suitable candidates are men who have undergone surgery or radiation for prostate cancer but now show rising PSA levels, suggesting a recurrence. Participants will be divided into two groups: one receiving the combination treatment and the other a placebo, for up to 24 months. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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, if you have been treated with certain prostate cancer drugs like enzalutamide or abiraterone in the past 18 months, you may not be eligible to participate.

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

Research shows that darolutamide, when combined with androgen deprivation therapy (ADT), is generally well-tolerated by patients. Studies have found that darolutamide significantly extends the time patients live without cancer spreading. Most side effects are mild to moderate. For instance, real-world data reveal that only a small number of patients needed to reduce their dose due to side effects. Additionally, darolutamide has already received approval for treating certain types of prostate cancer, indicating its safety for use. ^{1 2 3 4 5}

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

Researchers are excited about darolutamide combined with androgen deprivation therapy (ADT) for prostate cancer because this combination offers a unique mechanism of action. Unlike traditional treatments that mainly focus on reducing testosterone levels, darolutamide adds an extra layer by blocking androgens from binding to their receptors more effectively. This dual approach could potentially slow cancer progression more efficiently and with fewer side effects than existing options like enzalutamide or abiraterone. Additionally, darolutamide is known for having a favorable safety profile, which means it might cause fewer disruptions to daily life for patients.

What evidence suggests that the combination of darolutamide and ADT could be an effective treatment for prostate cancer?

In this trial, participants will receive either darolutamide with androgen deprivation therapy (ADT) or a placebo with ADT. Research has shown that darolutamide with ADT can significantly benefit prostate cancer patients. One study demonstrated that this combination increased the time patients lived without cancer progression by 40% compared to a placebo. Another study found that darolutamide with ADT reduced the risk of cancer worsening or death to 29%, compared to 42% with a placebo. This evidence suggests that adding darolutamide to ADT effectively slows prostate cancer. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for men over 18 with hormone-sensitive prostate cancer who've had a rise in PSA levels after local treatments like surgery or radiation. They must be generally healthy, able to consent, and willing to use contraception. Men with certain types of aggressive prostate cancer, previous extensive treatments, or recent other cancers are excluded.

Inclusion Criteria

Screening values of: Alanine aminotransferase (ALT) ≤1.5 x upper limit of normal (ULN); Aspartate aminotransferase (AST) ≤1.5 x ULN; Total bilirubin (TBL) ≤1.5 ULN, (except participants with a diagnosis of Gilbert's disease); Estimated glomerular filtration rate (eGFR) >40 ml/min/1.73 m^2 calculated by the CKD-EPI formula

My prostate cancer was first treated with surgery, possibly followed by radiation, or just radiation.

Serum testosterone ≥150 ng/dL (5.2 nmol/L) (local or central values accepted)

Exclusion Criteria

I haven't had PSMA-radiotherapy in the last 12 months.

I haven't had any cancer except for certain skin cancers or superficial bladder cancer in the last 5 years.

I completed radiotherapy less than 8 weeks ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either darolutamide plus ADT or placebo plus ADT for a pre-specified duration of 24 months

24 months

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including health checks and cancer status assessments

Approximately 1 month

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• ADT
• Darolutamide

Trial Overview

The study compares the effectiveness of darolutamide combined with ADT versus placebo plus ADT in preventing cancer progression. Participants will take these treatments orally for 24 months and undergo regular health checks including blood tests and advanced imaging scans to monitor their condition.

How Is the Trial Designed?

Group I: Darolutamide+ADT Experimental Treatment 2 Interventions

Participants will receive darolutamide plus ADT twice daily with food for a pre-specified duration of 24 months.

Group II: Placebo+ADT Placebo Group 2 Interventions

Participants will receive Placebo plus ADT twice daily with food for a pre-specified duration of 24 months.

ADT is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in United States as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in Canada as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in Japan as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in China as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in Switzerland as Androgen Deprivation Therapy for:

• 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

Published Research Related to This Trial

In a phase 3 trial involving 1509 men with nonmetastatic, castration-resistant prostate cancer, darolutamide significantly improved metastasis-free survival, with a median of 40.4 months compared to 18.4 months for placebo (hazard ratio 0.41).

The safety profile of darolutamide was comparable to placebo, with similar rates of adverse events and no increased risk of serious side effects like seizures or cognitive disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. Fizazi, K., Shore, N., Tammela, TL., et al.[2022]

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]

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 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]

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 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]

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 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]

Citations

1.

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 ...

2.

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 ...

3.

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 ...

4.

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 ...

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.

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 ...