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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new combination of two drugs, darolutamide (an androgen receptor inhibitor) and relugolix (a hormone therapy), is safe and practical for treating high-risk prostate cancer before surgery. The trial targets men diagnosed with aggressive prostate cancer that has not spread but is still considered high-risk. It is ideal for those confirmed to have high-risk prostate cancer and planning to undergo prostate removal surgery. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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.

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

Earlier studies have examined the use of relugolix with darolutamide in patients with hormone-sensitive prostate cancer. The findings suggest that this combination might be safe and effective. Some studies have shown that relugolix with similar treatments was generally well-tolerated by patients. However, this specific combination is still under investigation, and more information about its safety is being gathered. As this is a Phase 1 trial, the primary goal is to assess the treatment's safety and tolerability. Researchers are closely monitoring any side effects and patient responses. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of darolutamide and relugolix for prostate cancer because it represents a novel approach to treatment. Unlike standard treatments that often rely on surgery, radiation, or traditional hormone therapies, this combination leverages a unique mechanism. Darolutamide is an androgen receptor inhibitor, and relugolix is an oral GnRH antagonist, together aiming to provide a more targeted attack on cancer cells. This dual-action strategy could potentially enhance treatment effectiveness and reduce the side effects typically associated with prostate cancer therapies.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

This trial will evaluate the combination of darolutamide and relugolix as a neoadjuvant treatment before radical prostatectomy in patients with high-risk prostate cancer. Research has shown that this combination may be promising for treating prostate cancer. Darolutamide, when combined with treatments like chemotherapy (docetaxel) and hormone therapy, has effectively slowed advanced prostate cancer. Relugolix, a newer hormone therapy, has been tested with darolutamide and demonstrated effectiveness in patients with hormone-sensitive prostate cancer. Studies suggest that this combination can help control the disease before surgery, making the cancer easier to remove and potentially improving long-term outcomes. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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 (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 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]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK601835/

Darolutamide (Nubeqa) - NCBI Bookshelf - NIH Analyses of secondary outcomes supported the efficacy of darolutamide plus docetaxel and ADT in delaying progression to metastatic castration-resistant prostate ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-09937

Relugolix and Darolutamide in Hormone-sensitive Prostate ... This phase II trial tests the safety and effectiveness relugolix in combination with darolutamide in treating patients with hormone-sensitive prostate cancer.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06631521?term=AREA%5BConditionSearch%5D(%22Adenocarcinoma%22)%20AND%20AREA%5BInterventionSearch%5D(%22Relugolix%22)&rank=3

NCT06631521 | Neoadjuvant Darolutamide and Relugolix ... The goal of this clinical trial is to determine the safety and feasibility of a new combination of darolutamide and relugolix as neoadjuvant therapy ...

4. everyone.org everyone.org/explore/compare?id1=311&id2=412

Nubeqa (darolutamide) vs Orgovyx (relugolix) Patients treated with Nubeqa showed a median metastasis-free survival of 40.4 months, compared to 18.4 months for patients receiving a placebo. This marked ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40377869/

Relugolix in Combination with Androgen Receptor ... This review explores the real-world data and clinical studies evaluating relugolix coadministration with ARPIs, including enzalutamide, abiraterone, ...

6. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-prostate-cancer/158156-asco-gu-2025-novel-combination-of-neoadjuvant-darolutamide-and-relugolix-preceding-radical-prostatectomy-for-high-risk-localized-and-locally-advanced-prostate-cancer-phase-i-ib-trial.html

ASCO GU 2025: Novel Combination of Neoadjuvant ... Primary objective: Safety and feasibility of neoadjuvant darolutamide + relugolix followed by RP for local/locally advanced, high-risk prostate ...

7. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/545344

Neoadjuvant Darolutamide and Relugolix Combination ... The goal of this clinical trial is to determine the safety and feasibility of a new combination of darolutamide and relugolix as neoadjuvant therapy ...