Relugolix + Darolutamide for Prostate Cancer

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Atish D. Choudhury

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Atish Choudhury, MD

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

Disqualifiers: Brain metastases, Uncontrolled illness, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This research study is being done to determine the rate of testosterone recovery after completing two years of treatment with the combination of relugolix and darolutamide as well as to assess the safety of the drugs when administered in combination. The names of the drugs in this study are: * Relugolix (a type of gonadotropin-releasing hormone receptor antagonist) * Darolutamide (a type of androgen receptor antagonist)

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.

What data supports the effectiveness of the drug combination Relugolix and Darolutamide for prostate cancer?

Darolutamide has been shown to be effective in treating different stages of prostate cancer, including non-metastatic castration-resistant prostate cancer and metastatic hormone-sensitive prostate cancer, by prolonging survival and delaying disease progression. It is generally well-tolerated with a low risk of central nervous system side effects. ^{1 2 3 4 5}

Is the combination of Relugolix and Darolutamide 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 needed for patients with kidney or liver issues. ^{1 2 3 4 5}

What makes the drug combination of Relugolix and Darolutamide unique for prostate cancer treatment?

The combination of Relugolix and Darolutamide is unique because it combines two oral medications that target androgen receptors, which are crucial in prostate cancer growth, offering a potentially more effective approach by using both a non-steroidal androgen receptor antagonist (Darolutamide) and a gonadotropin-releasing hormone (GnRH) antagonist (Relugolix) to manage the disease. ^{1 2 4 6 7}

Research Team

Atish D. Choudhury

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

Trial Timeline

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)

Treatment Details

Interventions

• Darolutamide (Androgen Receptor Antagonist)
• Relugolix (Gonadotropin-Releasing Hormone Receptor Antagonist)

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.

Participant Groups

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 Canada for the following indications:

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+

Crystal S. Denlinger

National Comprehensive Cancer Network

Chief Executive Officer since 2023

MD, FACP

Robert W. Carlson

National Comprehensive Cancer Network

Chief Medical Officer since 2013

MD

Sumitomo Pharmaceuticals America

Industry Sponsor

Trials

5

Recruited

300+

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]

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, 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]

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]

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 Non-Metastatic Castration-Resistant Prostate Cancer. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

4. France pubmed.ncbi.nlm.nih.gov

Darolutamide: A Review in Metastatic Hormone-Sensitive Prostate Cancer. [2023]

5. 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]

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

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

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

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