Relugolix + Darolutamide for Prostate Cancer

Not currently recruiting at 2 trial locations

Overseen By Atish D. Choudhury

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Atish Choudhury, MD

Must not be taking: P-gp inducers, CYP3A4 inhibitors

Disqualifiers: Brain metastases, Uncontrolled illness, 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

Compensation: Varies

Number of Visits: 4

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the combination of two drugs, relugolix and darolutamide, to determine how quickly testosterone levels return to normal after two years of prostate cancer treatment. Researchers aim to ensure the safety of using these drugs together. The trial targets individuals with hormone-sensitive prostate cancer undergoing androgen deprivation therapy, which lowers male hormones. Participants must have prostate cancer confirmed through medical tests and should not show signs of the disease spreading to high volumes, such as the brain or major organs. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 taking certain medications that interact with the trial drugs, you may need to adjust or stop them. It's important to discuss your current medications with the trial team to ensure there are no harmful interactions.

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

Research shows that taking relugolix and darolutamide together is generally safe for patients. Studies have found that using these two drugs simultaneously does not introduce new safety issues. Patients taking both drugs did not experience more side effects than when taking each drug individually.

In everyday use, this combination has not caused new problems with drug interactions, suggesting its safety. While some side effects are common with most medications, no unusual or serious issues have emerged with this combination so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Relugolix and Darolutamide for prostate cancer because these drugs work together in a novel way to tackle the disease. Most treatments for prostate cancer, like androgen deprivation therapy, focus on reducing testosterone levels, but Relugolix is an oral medication that blocks the receptors directly, offering a potentially more immediate effect. Darolutamide, on the other hand, is a newer drug that inhibits the growth of cancer cells by blocking androgen receptors, with fewer side effects than older medications. Together, they offer a promising combination that might lead to better outcomes and improved quality of life for patients.

What evidence suggests that this treatment might be an effective treatment for prostate cancer?

Research has shown that combining relugolix and darolutamide may effectively treat prostate cancer. In this trial, participants will receive both drugs to evaluate their combined effectiveness. When used with androgen deprivation therapy (ADT), darolutamide can lower the risk of death in patients with metastatic hormone-sensitive prostate cancer by over 30%. Specifically, patients taking darolutamide lived without cancer spreading for an average of 40.4 months, much longer than those on a placebo. Relugolix helps manage hormone levels and does not interfere with other medications like darolutamide. This trial studies the potential of these drugs to improve treatment outcomes. Evidence suggests this combination could be highly effective for advanced prostate cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Atish D. Choudhury

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for men with prostate cancer who have completed two years of treatment. It's designed to see how quickly testosterone levels return to normal after stopping the drugs relugolix and darolutamide, which are used together in this study.

Inclusion Criteria

My prostate cancer responds to hormone therapy, and I am planned for an intensive 2-year treatment.

Participants must have the ability to understand and sign a written informed consent document

I can swallow pills.

Exclusion Criteria

My cancer has spread to my brain or other vital organs.

Participants who received prior systemic therapy for the disease state they are enrolling for

Participants who are receiving any other investigational agents for this condition

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 a combination of relugolix and darolutamide for 2 years

24 months

Monthly visits (in-person)

Follow-up

Participants are monitored for testosterone recovery and safety for 18 months after treatment

18 months

Every 3 months (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Darolutamide
• Relugolix

Trial Overview

The study tests the combination of two medications: Relugolix, which reduces certain hormone production, and Darolutamide, which blocks hormones that can fuel cancer growth. The focus is on recovery rates of testosterone after treatment.

How Is the Trial Designed?

Group I: Cohort 2 Long Pharmacokinetics (PK) Experimental Treatment 2 Interventions

Enrolled participants will complete study procedures as follows: * Cycle 1: * Days 1, 2, 8 of 28 Day Cycle: Predetermined dose of Relugolix 1x daily. First dose will be administered in-clinic. * Days 1, 2, 8 of 28 Day Cycle: Predetermined dose of Darolutamide 2x daily. First dose will be administered in-clinic. * Cycle 2: * Day 1 of 28 Day Cycle: Predetermined dose of Relugolix 1x daily. First dose will be administered in-clinic. * Day 1 of 28 Day Cycle: Predetermined dose of Darolutamide 2x daily. First dose will be administered in-clinic. * Cycle 3 through End of Treatment: * Predetermined dose of Relugolix 1x daily. * Predetermined dose of Darolutamide 2x daily. * End of Treatment visit. * Follow Up: every 3 months for 18 months.

Group II: Cohort 1 Short Pharmacokinetics (PK) Experimental Treatment 2 Interventions

Enrolled participants will complete study procedures as follows: * Cycle 1: * Day 1 of 28 Day Cycle: Predetermined dose of Relugolix 1x daily. First dose will be administered in-clinic. * Day 1 of 28 Day Cycle: Predetermined dose of Darolutamide 2x daily. First dose will be administered in-clinic. * Cycle 2 through End of Treatment: * Predetermined dose of Relugolix 1x daily. * Predetermined dose of Darolutamide 2x daily. * End of Treatment visit. * Follow Up: every 3 months for 18 months.

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?

Atish Choudhury, MD

Lead Sponsor

Trials

1

Recruited

30+

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

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Sumitomo Pharma America, Inc.

Industry Sponsor

Trials

244

Recruited

51,500+

Jatin Shah

Sumitomo Pharma America, Inc.

Chief Medical Officer since 2024

MD from an unspecified institution

Tsutomu Nakagawa

Sumitomo Pharma America, Inc.

Chief Executive Officer since 2024

MBA from Waseda University

National Comprehensive Cancer Network

Collaborator

Trials

121

Recruited

7,400+

Sumitomo Pharmaceuticals America

Industry Sponsor

Trials

5

Recruited

300+

Published Research Related to This Trial

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]

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 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 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 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

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11308532/

Management of Advanced Prostate Cancer With Relugolix

Relugolix is not expected to cause clinically meaningful changes in exposure with concomitant use of abiraterone, docetaxel, darolutamide, or enzalutamide.

2.

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 ...

3.

onclive.com

onclive.com/view/darolutamide-plus-adt-is-efficacious-in-mhspc-regardless-of-disease-volume

Darolutamide Plus ADT Is Efficacious in mHSPC ...

“The phase 3 ARASENS study [NCT02799602] demonstrated a greater than 30% reduction in the risk of death with the combination of darolutamide ...

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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.

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 ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12307536/

Relugolix in Combination with Androgen Receptor ...

The results of a phase II sub-study demonstrate that the coadministration of relugolix and apalutamide effectively maintained castrate ...

7.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.85

Real-world experience on tolerability and safety of ...

The combination has a favorable safety and tolerability profile with no new safety concerns. No new DDI concerns were raised.

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06463457?term=AREA%5BInterventionSearch%5D(ORGOVYX)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=9

Comeback From Long coursE Androgen Deprivation ...

This research study is being done to determine the rate of testosterone recovery after completing two years of treatment with the combination of relugolix ...

9.

cancer.gov

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

Relugolix and Darolutamide in Hormone-sensitive Prostate ...

Giving relugolix in combination with darolutamide may be safe and effective in treating in patients with hormone-sensitive prostate cancer. Eligibility Criteria ...

10.

onclive.com

onclive.com/view/optyx-study-offers-preliminary-glance-into-real-world-use-of-relugolix-in-advanced-prostate-cancer

OPTYX Study Offers Preliminary Glance Into Real-World ...

Data from OPTYX showed that most patients (52.2%) in the overall population (n = 999) received relugolix in combination with other prostate ...