Darolutamide + Hormone Therapy for Prostate Cancer

Overseen By Clinical Trials Intake

Age: 18+

Sex: Male

Trial Phase: Phase 4

Sponsor: University of Chicago

Must be taking: LHRH agonists/antagonists

Must not be taking: Chemotherapy, PARP inhibitors

Disqualifiers: Active infection, Heart failure, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how combining darolutamide (a medication for prostate cancer) with hormone therapy affects physical activity in men with metastatic hormone-sensitive prostate cancer. Researchers focus on tracking step counts and their relation to health and safety markers. The trial seeks men with prostate cancer that has spread and who exhibit signs of frailty, such as significant weight loss or difficulties with daily activities. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients.

Do I need to stop my current medications for the trial?

The trial requires that any first-generation antiandrogen medications be stopped before starting the study treatment or within 45 days of starting these treatments. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

What is the safety track record for darolutamide?

Research has shown that darolutamide, when combined with hormone therapy, is generally safe. Most patients experienced only mild to moderate side effects. In one study, only a small number of patients needed to lower their dose due to side effects, which were usually mild, such as tiredness or nausea, and could be managed. Overall, patients with prostate cancer have tolerated darolutamide well. The FDA has approved the treatment for other prostate cancer conditions, indicating a strong safety record. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Darolutamide is unique because it specifically targets the androgen receptor, which plays a key role in the progression of prostate cancer. This is different from many standard treatments that primarily focus on reducing androgen production through hormone therapy. Researchers are excited about this treatment because it may offer a more targeted approach, potentially leading to fewer side effects and improved quality of life. Additionally, the trial's focus on understanding the correlation between darolutamide, hormone therapy, and physical activity could provide valuable insights into enhancing patient well-being.

What is the effectiveness track record for darolutamide in treating prostate cancer?

Studies have shown that darolutamide, when combined with hormone therapy, significantly improves outcomes for prostate cancer patients. Specifically, it has increased the time patients live without their cancer worsening by 40%. In this trial, participants will receive darolutamide alongside hormone therapy to assess its effects on physical activity, with a focus on monitoring step count. Darolutamide works particularly well with androgen deprivation therapy (ADT), a common hormone treatment, to slow cancer growth. Additionally, darolutamide has been approved for use in a type of prostate cancer that still responds to hormone therapy, demonstrating its effectiveness in this condition. These findings suggest darolutamide could be a promising treatment option for managing prostate cancer. ^{1 3 4 6 7}

Who Is on the Research Team?

Russell Szmulewitz, MD

Principal Investigator

University of Chicago Medicine Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with metastatic hormone-sensitive prostate cancer who have been positively identified by a brief geriatric assessment. Specific eligibility details are not provided, but typically participants must meet certain health standards and may be excluded based on other medical conditions or treatments.

Inclusion Criteria

Patients must consent and concurrently accrue to the IRONMAN registry study

I am using two reliable birth control methods if I or my partner can have children.

I can take care of myself but can't do heavy physical work.

Exclusion Criteria

Use of other investigational drugs within 30 days prior to randomization

Inability to complete the study imaging procedures

I have had prostate cancer treatment, but not with the drugs excluded.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive darolutamide in combination with androgen deprivation therapy to assess its impact on physical activity and safety markers

6 months

Regular visits for monitoring step count and health assessments

Extended Treatment Monitoring

Continued monitoring of step count, grip strength, and other health parameters

6 months

Visits at 3, 6, 9, and 12 months for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Darolutamide

Trial Overview

The study is testing the effectiveness of darolutamide combined with standard hormone therapy in managing prostate cancer. It focuses on how this combination affects physical activity levels, specifically step count, and monitors safety markers in patients.

How Is the Trial Designed?

Group I: Darolutamide and physical activity correlation Experimental Treatment 2 Interventions

To understand how darolutamide plus hormone therapy affects physical activity, we would like to specifically monitor the step count of men receiving these medications.

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?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

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 (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]

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 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, 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, 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]

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.

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 ...