Darolutamide + Relugolix for Prostate Cancer

Overseen By AdventHealth Oncology Research

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: AdventHealth

Must not be taking: Chemotherapy, Radiotherapy, Antivirals, others

Disqualifiers: Stroke, Myocardial infarction, Angina, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to determine the safety and feasibility of a new combination of darolutamide and relugolix as neoadjuvant therapy preceding radical prostatectomy (RP) for high-risk prostate cancer (PCa) in adult males.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on drugs that strongly affect liver enzymes (CYP3A4), you may need to stop or switch them before starting the trial. 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 improve survival in men with non-metastatic castration-resistant prostate cancer and metastatic hormone-sensitive prostate cancer when used with other therapies, according to clinical trials. It is generally well-tolerated and has a low risk of causing side effects related to the brain. ^{1 2 3 4 5}

Is the combination of Darolutamide and Relugolix safe for humans?

Darolutamide has been shown to be generally well tolerated in clinical trials for prostate cancer, with a low risk of central nervous system side effects and manageable overall side effects. It is important to note that dose adjustments may be necessary for patients with kidney or liver issues. ^{1 2 3 4 6}

How is the drug combination of Darolutamide and Relugolix unique for prostate cancer treatment?

The combination of Darolutamide and Relugolix for prostate cancer is unique because Darolutamide is a novel androgen receptor inhibitor that has shown effectiveness in both metastatic and non-metastatic prostate cancer, while Relugolix is an oral medication that reduces testosterone levels, potentially offering a more convenient and less invasive option compared to traditional hormone therapies. ^{1 2 3 5 7}

Eligibility Criteria

Men over 18 with high-risk prostate cancer who can swallow pills and have good performance status (able to carry out daily activities). They must have adequate organ function, be candidates for surgery to remove the prostate, and not have had certain treatments or other cancers recently.

Inclusion Criteria

I am fully active or can carry out light work.

I am eligible for radical prostatectomy.

I am a man aged 18 or older.

Exclusion Criteria

I haven't had chemotherapy or radiotherapy in the last 4 weeks.

Histologic variants comprising more than 50% of the sample as determined by pathology review

Receiving any other investigational agents

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive a combination of darolutamide and relugolix as neoadjuvant therapy before radical prostatectomy

12 weeks

Radical Prostatectomy

Participants undergo radical prostatectomy following neoadjuvant treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Treatment Details

Interventions

• Darolutamide
• Relugolix

Trial Overview The trial is testing a new combination of two drugs, darolutamide and relugolix, given before surgery to remove the prostate in men with aggressive prostate cancer. The aim is to see if it's safe and doable as a pre-surgery treatment.

Participant Groups

Group I: Combination Therapy Arm Experimental Treatment 3 Interventions

This arm is designed to evaluate the safety and feasibility of the combination therapy using darolutamide and relugolix as neoadjuvant treatment before radical prostatectomy (RP) in patients with high-risk prostate cancer (PCa).

Who Is Running the Clinical Trial?

AdventHealth

Lead Sponsor

Trials

118

Recruited

31,800+

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

Sumitomo Pharma Switzerland

Collaborator

Trials

1

Recruited

30+

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 is an effective treatment for nonmetastatic castration-resistant prostate cancer and metastatic hormone-sensitive prostate cancer, with potential for broader use in other stages of prostate cancer due to its favorable pharmacokinetic properties.

One of the key advantages of darolutamide is its low distribution to the brain, which reduces the risk of seizures and central nervous system side effects, making it a safer option compared to other androgen receptor signaling inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics and Pharmacodynamics of the Next Generation Androgen Receptor Inhibitor-Darolutamide. Podgoršek, E., Mehra, N., van Oort, IM., et al.[2023]

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, 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]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics and Pharmacodynamics of the Next Generation Androgen Receptor Inhibitor-Darolutamide. [2023]

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

Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. [2023]

6. 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]

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

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