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

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This prospective clinical trial aims to investigate the impact of darolutamide in combination with standard-of-care androgen deprivation on physical activity, specifically step count, and its correlation with important markers of safety in vulnerable adults who screen positive by a brief geriatric assessment (GA) and metastatic hormone-sensitive prostate cancer.

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

Darolutamide has been shown to be effective in treating prostate cancer by delaying the spread of the disease and improving survival rates. In clinical trials, it was effective in both non-metastatic and metastatic hormone-sensitive prostate cancer, especially when used with other therapies like hormone therapy and chemotherapy. ^{1 2 3 4 5}

Is Darolutamide safe for humans?

Darolutamide has been shown to be generally safe and well-tolerated in clinical trials for prostate cancer, with a manageable side effect profile. It does not cross the blood-brain barrier, reducing the risk of seizures, and has a low likelihood of causing central nervous system-related side effects. ^{1 2 3 4 6}

What makes the drug Darolutamide unique for treating prostate cancer?

Darolutamide is unique because it is a non-steroidal androgen receptor antagonist that has minimal penetration into the brain, reducing the risk of central nervous system side effects compared to other similar drugs. It is effective in both non-metastatic castration-resistant and metastatic hormone-sensitive prostate cancer, offering a new option for patients with these conditions. ^{1 2 3 7 8}

Research Team

Russell Szmulewitz, MD

Principal Investigator

University of Chicago Medicine Comprehensive Cancer Center

Eligibility Criteria

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 am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

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]

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 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 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]

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]

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. 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]

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

Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

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

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

Clinical Development of Darolutamide: A Novel Androgen Receptor Antagonist for the Treatment of Prostate Cancer. [2019]