Darolutamide + ADT for Prostate Cancer

Not currently recruiting at 120 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: ECOG-ACRIN Cancer Research Group

Must be taking: ADT

Must not be taking: Chemotherapy

Disqualifiers: Lymph node involvement, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining darolutamide (Nubeqa) with ADT (a treatment that lowers testosterone) is more effective at treating high-risk prostate cancer after surgery than ADT alone. Darolutamide blocks testosterone’s effects, which is crucial because testosterone can promote prostate cancer growth. The trial seeks participants who have undergone prostate surgery and show no signs of cancer spreading or returning. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must not have had any previous treatment with androgen deprivation therapy (ADT), chemotherapy, or other systemic therapy for prostate cancer.

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

Research shows that darolutamide, when combined with hormone therapy (ADT), is generally well-tolerated by patients. Previous studies found that most side effects were mild to moderate, including rash, tiredness, and hot flashes. Serious side effects were uncommon, affecting only about 7.4% of patients. Notably, the FDA has approved darolutamide for other types of prostate cancer, indicating thorough testing and safety for broader use in those cases. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about darolutamide for prostate cancer because it offers a unique approach compared to traditional treatments like surgery, radiation, or other hormone therapies. Darolutamide is an androgen receptor inhibitor, which means it specifically blocks the receptors that prostate cancer cells rely on to grow, potentially leading to more effective control of the disease. Unlike some other treatments, darolutamide has shown a favorable side effect profile, which might mean fewer disruptions to patients' daily lives. This targeted action combined with a potentially better tolerance makes darolutamide a promising option for those battling prostate cancer.

What evidence suggests that darolutamide with ADT might be an effective treatment for prostate cancer?

Research has shown that adding darolutamide to androgen deprivation therapy (ADT) effectively treats prostate cancer. In this trial, participants in Arm B will receive this combination, which has helped patients live 40% longer without their cancer worsening compared to those who received a placebo. Specifically, fewer men experienced cancer progression or death when using darolutamide with ADT than with ADT alone, the treatment for participants in Arm A. The treatment blocks hormones like testosterone, which play a role in prostate cancer development. These findings suggest that darolutamide could significantly enhance current prostate cancer treatments. ^{2 3 5 6 7}

Who Is on the Research Team?

Alicia K Morgans

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

Men with high-risk prostate cancer who've had surgery (radical prostatectomy) can join this trial. They should have a good performance status, no major health issues that could affect the study, and no previous prostate cancer treatments. Their PSA levels must be undetectable and they need to meet specific criteria based on tests like Decipher score and CAPRA-S score.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

I have a CAPRA-S score of 3 or higher and no lymph node involvement.

Glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2 (obtained within 4 weeks prior to registration)

Exclusion Criteria

I have no signs of cancer spread in my body based on recent scans.

I do not have any severe illnesses or conditions that are not under control.

I have not received hormone therapy, chemotherapy, or any other systemic treatment for my prostate cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ADT and either darolutamide or placebo for 12 months

52 weeks

Injections every 1, 3, or 4 months; daily oral administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Darolutamide

Trial Overview The ERADICATE Study is testing if adding Darolutamide to standard hormonal therapy (ADT) after surgery is more effective than ADT alone in men with high-risk prostate cancer. It's a phase III trial aiming to see if this combination better reduces or eliminates the risk of cancer returning.

How Is the Trial Designed?

Group I: Arm B (ADT, darolutamide) Experimental Treatment 5 Interventions

Patients receive goserelin acetate, leuprolide acetate, or triptorelin via injection every 3 months for 12 months (4 injections), every 4 months for 12 months (3 injections), or every month for 12 months (12 injections) in the absence of disease progression or unacceptable toxicity. Patients also receive darolutamide QID for 52 weeks in the absence of disease progression or unacceptable toxicity.

Group II: Arm A (ADT, placebo) Active Control 5 Interventions

Patients receive goserelin acetate, leuprolide acetate, or triptorelin via injection every 3 months for 12 months (4 injections), every 4 months for 12 months (3 injections), or every month for 12 months (12 injections) in the absence of disease progression or unacceptable toxicity. Patients also receive a placebo four times daily (QID) for 52 weeks in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 is an investigational oral medication that acts as a high-affinity androgen receptor antagonist, showing promising antitumor activity and a favorable safety profile in early-phase trials for advanced prostate cancer.

Unlike other antiandrogens, darolutamide has minimal penetration of the blood-brain barrier and does not significantly increase serum testosterone levels, which may provide advantages in treating patients with resistance to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide (ODM-201) for the treatment of prostate cancer. Shore, ND.[2018]

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]

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 (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. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-metastatic-castration-sensitive-prostate-cancer

FDA approves darolutamide for metastatic castration ... Treatment with darolutamide resulted in a statistically significant improvement in rPFS compared to placebo. Median rPFS was not reached in the ...

2. bayer.com bayer.com/en/us/news-stories/new-data-for-nubeqa

New Data for NUBEQA® Build on Safety and Efficacy ... NUBEQA (darolutamide) plus androgen deprivation therapy (ADT) improved radiological progression-free survival (rPFS) by 40% (HR 0.60; 95% CI: 0.44-0.80) and 70 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40310703/

Real-world effectiveness of darolutamide in metastatic ... Darolutamide suppressed serum PSA levels by >50% in 5/44 M1-CRPC patients (11.4%), all previously 2GARA-naïve. M1-CRPC patients resistant only ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e17108

Real world outcomes of darolutamide efficacy and safety in ... Common side effects included rash, fatigue, hot flushes, and sweating, with 7.4% (n=14) experiencing grade 2 adverse events and 0.5% (n=1) with ...

5. nubeqa-us.com nubeqa-us.com/about-nubeqa/mcspc-study-results

Clinical Study | NUBEQA® (darolutamide) | Patient Website At the time of analysis, 29% (128 out of 446) of men taking NUBEQA + ADT had cancer worsening via scans or were no longer living compared to 42% (94 out of 223) ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37660438/

Efficacy and safety outcomes of darolutamide in patients ... Darolutamide significantly improved median metastasis-free survival by nearly 2 years and reduced the risk of death by 31% versus placebo, with a favourable ...

7. nature.com nature.com/articles/s41391-025-01047-7

DARolutamide ObservationaL (DAROL) study in patients ... Darolutamide showed consistent safety and effectiveness in DAROL vs ARAMIS. Most treatment-emergent adverse events were grade 1/2. Two-year ...