Darolutamide + ADT for Metastatic Hormone-Sensitive Prostate Cancer

(ARASEC Trial)

Recruiting at 50 trial locations

Overseen By Bayer Clinical Trials Contact

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Bayer

Must be taking: ADT

Must not be taking: Relugolix, 5-alpha reductase inhibitors

Disqualifiers: Recent malignancy, Cardiac events, Brain metastases, 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: Unknown

Duration: Approximately 12 months

223 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to assess if the addition of darolutamide to ADT compared with ADT alone would result in superior clinical efficacy in participants with metastatic hormone-sensitive prostate cancer (mHSPC) by progression-free survival. The researchers want to learn how long it takes for the cancer to get worse (also known as "progression-free survival") by either increasing symptoms, new metastases, PSA rise or death. All participants will be on treatment and take darolutamide with ADT until their cancer spreads, they have a medical problem, or they leave the study. The results will then be compared with patients' results from another study who received ADT alone (CHAARTED). This study will also assess safety by gathering adverse event information throughout the duration of the study. An adverse event is any medical problem, related or not to study treatment that a participant has during a study. The study drug, darolutamide, is already available for doctors to prescribe to patients with prostate cancer that has not yet spread to other parts of the body. It works by blocking a protein called a receptor from attaching to a hormone called androgen that is found in men. This protein can also be found in prostate cancer cells. ADT is a treatment that doctors are currently able to prescribe to patients with mHSPC. ADT is used to lower the amount of the androgen hormone.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop taking your current medications, but certain medications like relugolix and 5-alpha reductase inhibitors must not be used. It's best to discuss your current medications with the trial team to ensure they don't interfere with the study.

What data supports the effectiveness of the drug Darolutamide + ADT for Metastatic Hormone-Sensitive Prostate Cancer?

Research shows that Darolutamide, when combined with ADT and another drug called docetaxel, helps patients with metastatic hormone-sensitive prostate cancer live longer compared to those who only receive ADT and docetaxel. This combination is generally well-tolerated and offers a new option for treating this type of cancer. ^{1 2 3 4 5}

Is Darolutamide safe for humans?

Darolutamide, used with hormone therapy (ADT) and sometimes with docetaxel, has been generally well tolerated in clinical trials for prostate cancer. The side effects reported are consistent with those of other similar treatments, and it has a low chance of causing brain-related side effects compared to other drugs in its class. ^{1 2 5 6 7}

What makes the drug Darolutamide + ADT unique for treating metastatic hormone-sensitive prostate cancer?

Darolutamide is a unique oral drug that blocks androgen receptors (proteins that help cancer cells grow) and is used with hormone therapy (ADT) to treat metastatic hormone-sensitive prostate cancer. It has shown to improve survival rates when combined with ADT and chemotherapy (docetaxel), offering a new option for patients with high-volume disease. ^{1 2 3 4 5}

Eligibility Criteria

Men with metastatic hormone-sensitive prostate cancer who have started ADT up to 120 days before joining. They must have good organ function, no severe recent surgeries, and an ECOG Performance Status of 0-2. Excluded are those with certain other cancers in the last 5 years, brain metastases, uncontrolled hypertension, or previous treatments that could interfere.

Inclusion Criteria

I have taken medication to prevent flare before starting hormone therapy.

It's been over 4 weeks since my last major surgery and I've recovered from it.

I've had hormone therapy before surgery or alongside other treatments, meeting all required conditions.

Exclusion Criteria

I have not had cancer in the last 5 years, except for skin cancer.

My high blood pressure is not under control.

I have cancer that has spread to my brain or its coverings.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive darolutamide plus ADT until cancer progression, medical problem, or withdrawal

Approximately 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Long-term Follow-up

Participants are monitored for overall survival and radiographic progression-free survival

24 months

Treatment Details

Interventions

• ADT
• Darolutamide

Trial Overview The trial is testing if adding darolutamide to standard ADT improves progression-free survival compared to ADT alone in men with mHSPC. Progression-free survival means how long patients live without their cancer getting worse.

Participant Groups

Group I: Darolutamide+ADT Experimental Treatment 2 Interventions

Participants will receive darolutamide plus ADT in the ARASEC treatment arm. The control arm for the study will be derived from the participants treated with ADT alone in the CHAARTED trial using a matching approach

ADT is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in United States as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in Canada as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in Japan as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in China as Androgen Deprivation Therapy for:

• Prostate Cancer

Approved in Switzerland as Androgen Deprivation Therapy for:

• 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

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 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]

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 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]

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

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

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

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

5. France pubmed.ncbi.nlm.nih.gov

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

6. Canada pubmed.ncbi.nlm.nih.gov

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

7. Spain pubmed.ncbi.nlm.nih.gov

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