Darolutamide + ADT for Prostate Cancer

(ARANOTE Trial)

Recruiting at 180 trial locations

Overseen By Bayer Clinical Trials Contact

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Bayer

Must be taking: Androgen deprivation therapy

Must not be taking: Second-gen AR inhibitors, Chemotherapy

Disqualifiers: Stroke, Myocardial infarction, Uncontrolled hypertension, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 36 months

669 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a drug called darolutamide combined with a common hormone-lowering therapy in patients whose prostate cancer has spread but still responds to hormones. The goal is to see if this combination can effectively and safely slow down the cancer's growth. Darolutamide was approved in 2019 for a specific type of prostate cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those who have used certain prostate cancer treatments or high-dose corticosteroids recently. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Darolutamide + ADT for prostate cancer?

Research shows that Darolutamide, when combined with ADT, significantly prolongs survival in men with prostate cancer, both in non-metastatic and metastatic cases. In clinical trials, this combination has been effective in delaying the spread of cancer and improving overall survival, making it a promising option for treating prostate cancer. ^{1 2 3 4 5}

Is Darolutamide + ADT safe for humans?

Darolutamide, when used with androgen deprivation therapy (ADT), has been shown to have a manageable safety profile in clinical trials for prostate cancer. The side effects reported are generally consistent with those of ADT and other similar treatments, and it has a low risk of causing issues related to the central nervous system (brain and spinal cord). ^{1 2 4 5 6}

What makes the drug darolutamide unique for prostate cancer treatment?

Darolutamide is a novel, second-generation androgen receptor inhibitor that is structurally distinct and has a low risk of causing central nervous system side effects, making it a promising option for treating non-metastatic castration-resistant prostate cancer when combined with androgen deprivation therapy. ^{1 2 4 5 7}

Eligibility Criteria

Men with confirmed metastatic hormone-sensitive prostate cancer, who have started ADT within the last 12 weeks and are in good physical condition (ECOG PS of 0-2) can join. They must not have had certain heart conditions or other cancer treatments like chemotherapy for prostate cancer in the past 6 months.

Inclusion Criteria

I am able to care for myself and perform daily activities.

My bone marrow, liver, and kidneys are functioning well.

I started hormone therapy for cancer not more than 12 weeks ago.

Exclusion Criteria

I have not had radiotherapy in the last 2 weeks.

I cannot swallow pills.

I have not used specific hormone therapies, chemotherapy, or other treatments for prostate cancer recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive darolutamide or placebo in combination with androgen deprivation therapy (ADT)

36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 55 months

Treatment Details

Interventions

• Androgen Deprivation Therapy (ADT)
• Darolutamide

Trial Overview The trial is testing if adding Darolutamide to standard ADT improves outcomes for men with metastatic hormone-sensitive prostate cancer compared to ADT alone. Participants will either receive Darolutamide or a placebo alongside their regular ADT treatment.

Participant Groups

Group I: Darolutamide+ADT Experimental Treatment 2 Interventions

Participants will receive darolutamide 600 mg (2 tablets of 300 mg) twice daily with food and ADT of investigator's choice as standard therapy

Group II: Placebo+ADT Placebo Group 2 Interventions

Participants will receive placebo twice daily with food and ADT of investigator's choice as standard therapy

Androgen Deprivation Therapy (ADT) is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Androgen Deprivation Therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Non-metastatic high-risk prostate cancer

Approved in United States as Androgen Deprivation Therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Non-metastatic high-risk prostate cancer

Approved in Canada as Androgen Deprivation Therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Non-metastatic high-risk prostate cancer

Who Is Running the Clinical Trial?

Bayer

Lead 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

Orion Corporation, Orion Pharma

Industry Sponsor

Trials

140

Recruited

45,200+

Liisa Hurme

Orion Corporation, Orion Pharma

Chief Executive Officer since 2022

PhD in Biochemistry, University of Helsinki

Hilpi Rautelin

Orion Corporation, Orion Pharma

Chief Medical Officer since 2023

MD, University of Turku

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]

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]

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 FDA-approved nonsteroidal androgen inhibitor specifically for treating castration-resistant non-metastatic prostate cancer, providing a new option for patients whose PSA levels are rising despite low testosterone.

When used alongside androgen deprivation therapy (ADT), darolutamide, like other newer agents in its class, has been shown to prolong metastasis-free survival and median survival, making it an effective treatment choice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using darolutamide in advanced prostate cancer: How I Do It. Hamilton, J.[2021]

Darolutamide is a new nonsteroidal androgen receptor inhibitor approved for treating nonmetastatic castration-resistant prostate cancer (nmCRPC), showing promise as a second-generation antiandrogen.

The drug received FDA approval in July 2019 and is currently undergoing further evaluation in the E.U., highlighting its potential as a significant treatment option for men with nmCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide for treatment of castration-resistant prostate cancer. Rhea, LP., Mendez-Marti, S., Aragon-Ching, JB.[2020]

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]

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

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

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

Darolutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. [2022]

5. Canada pubmed.ncbi.nlm.nih.gov

Using darolutamide in advanced prostate cancer: How I Do It. [2021]

6. Spain pubmed.ncbi.nlm.nih.gov

Darolutamide for treatment of castration-resistant prostate cancer. [2020]

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

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