Darolutamide + ADT for Prostate Cancer

Recruiting at 116 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

27 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase III trial compares the effect of adding darolutamide to ADT versus ADT alone after surgery for the treatment of high-risk prostate cancer. ADT reduces testosterone levels in the blood. Testosterone is a hormone made mainly in the testes and is needed to develop and maintain male sex characteristics, such as facial hair, deep voice, and muscle growth. It also plays role in prostate cancer development. Darolutamide blocks the actions of the androgens (e.g. testosterone) in the tumor cells and in the body. Giving darolutamide with ADT may work better in eliminating or reducing the size of the cancer and/or prevent it from returning compared to ADT alone in patients with prostate cancer.

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.

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

Darolutamide, when combined with androgen deprivation therapy (ADT), has been shown to significantly prolong survival in men with both non-metastatic and metastatic prostate cancer, according to clinical trials. It is generally well tolerated and offers an important treatment option for patients at high risk of cancer spreading. ^{1 2 3 4 5}

Is darolutamide safe for humans?

Darolutamide, used with androgen deprivation therapy (ADT), has been generally well tolerated in clinical trials for prostate cancer, with a low chance of causing central nervous system-related side effects compared to similar treatments. Its safety profile is considered manageable, and adverse events are consistent with those of other treatments like ADT and docetaxel. ^{1 2 3 4 6}

How does the drug Darolutamide + ADT differ from other prostate cancer treatments?

Darolutamide is unique because it is a non-steroidal androgen receptor antagonist that has minimal penetration into the brain, reducing the risk of central nervous system side effects compared to other similar drugs. It is used in combination with androgen deprivation therapy (ADT) and has shown effectiveness in prolonging survival in both non-metastatic and metastatic prostate cancer, offering a new option for patients with high-risk or advanced disease. ^{1 2 3 5 7}

Research Team

Alicia K Morgans

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 (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 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 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 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]

References

1. France pubmed.ncbi.nlm.nih.gov

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

2. New Zealand pubmed.ncbi.nlm.nih.gov

Darolutamide: First Approval. [2020]

3. France pubmed.ncbi.nlm.nih.gov

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

4. 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]

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. England pubmed.ncbi.nlm.nih.gov

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