Androgen Receptor Antagonists for Prostate Cancer

Overseen By David Einstein, MD

Age: 18+

Sex: Male

Trial Phase: Phase < 1

Sponsor: Beth Israel Deaconess Medical Center

Must be taking: AR antagonists

Must not be taking: Older AR antagonists

Disqualifiers: High disease burden, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

15 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this research study is to determine whether hormonal therapies used early in the course of prostate cancer could increase the amount of Prostate-Specific Membrane Antigen (PSMA) as detected by PET/CT scans for participants with recurrent prostate cancer. This study will measure PSMA levels using standard PET/CT scans and participants will receive standard-of-care androgen receptor antagonist monotherapy. The names of the treatment interventions involved in this study are: * Androgen receptor antagonist monotherapy. * PSMA PET/CT scan It is expected that about 15 people will take part in this research study. Participation in this research study is expected to last about 4 weeks.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop your current medications, but you must be suitable for androgen receptor antagonist therapy and not have any drug interactions with the study medications.

What data supports the effectiveness of the drugs Apalutamide, Darolutamide, and Enzalutamide for prostate cancer?

Research shows that Darolutamide, Apalutamide, and Enzalutamide are effective in treating prostate cancer. Darolutamide has been shown to reduce tumor growth and improve survival in prostate cancer models. Apalutamide and Enzalutamide have also improved survival rates in patients with castration-resistant prostate cancer. ^{1 2 3 4 5}

Is 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-related side effects compared to other similar treatments. ^{1 2 4 6 7}

What makes the drug darolutamide unique for prostate cancer treatment?

Darolutamide is unique because it is a structurally distinct androgen receptor antagonist that effectively delays metastasis and death in non-metastatic castration-resistant prostate cancer, with a low risk of central nervous system side effects compared to other similar drugs. ^{1 2 6 8 9}

Research Team

David J. Einstein, MD

Principal Investigator

Beth Israel Deaconess Medical Center

Eligibility Criteria

Men aged 40+ with prostate cancer previously treated but now showing rising PSA levels indicating recurrence. They must have a PSMA PET/CT scan suggesting recurrent cancer, normal testosterone levels, and be prescribed standard AR antagonist therapy (apalutamide, darolutamide, or enzalutamide) by their doctor.

Inclusion Criteria

My doctor has prescribed me a specific prostate cancer medication.

My scan shows at least one area that might mean my prostate cancer has come back.

I am over 40, had prostate cancer treatment, and my PSA levels are rising.

Exclusion Criteria

I cannot receive AR antagonist therapy.

My condition requires urgent treatment due to severe symptoms or high disease burden.

I am not taking older AR blockers like bicalutamide for my condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive androgen receptor antagonist monotherapy and undergo PSMA PET/CT scans

4 weeks

2 visits (in-person) at weeks 1 and 4

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

Treatment Details

Interventions

• Apalutamide [Erleada], darolutamide [Nubeqa], or enzalutamide [Xtandi]
• Prostate-Specific Membrane Antigen (PSMA) PET/CT Scan

Trial Overview This study tests if early hormonal therapies increase PSMA detected by PET/CT scans in men with recurring prostate cancer. About 15 participants will receive standard AR antagonist monotherapy and undergo PSMA level measurements for approximately 4 weeks.

Participant Groups

Group I: Androgen Receptor Antagonist Monotherapy Experimental Treatment 2 Interventions

* Participants will receive pre-determined doses of apalutamide, darolutamide, or enzalutamide per standard care. * Participants will undergo Prostate-Specific Membrane Antigen (PSMA) PET/CT scans at weeks 1 and 4.

Apalutamide [Erleada], darolutamide [Nubeqa], or enzalutamide [Xtandi] is already approved in United States, European Union for the following indications:

Approved in United States as Xtandi for:

• Nonmetastatic castration-resistant prostate cancer
• Metastatic castration-resistant prostate cancer
• Nonmetastatic castration-sensitive prostate cancer with biochemical recurrence

Approved in United States as Erleada for:

• Nonmetastatic castration-resistant prostate cancer
• Metastatic castration-sensitive prostate cancer

Approved in United States as Nubeqa for:

• Nonmetastatic castration-resistant prostate cancer

Approved in European Union as Xtandi for:

• Metastatic castration-resistant prostate cancer
• Nonmetastatic castration-resistant prostate cancer

Approved in European Union as Erleada for:

• Nonmetastatic castration-resistant prostate cancer

Approved in European Union as Nubeqa for:

• Nonmetastatic castration-resistant prostate cancer

Who Is Running the Clinical Trial?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

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 is a novel androgen receptor antagonist that effectively targets both wild type and mutant androgen receptors associated with prostate cancer, showing strong competitive antagonism in cell-based assays.

In both in vitro and in vivo studies, darolutamide significantly reduced prostate cancer cell viability and tumor growth, indicating its potential as an effective treatment option for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide is a potent androgen receptor antagonist with strong efficacy in prostate cancer models. Sugawara, T., Baumgart, SJ., Nevedomskaya, E., et al.[2020]

In the SPARTAN study involving 1207 patients with nonmetastatic castration-resistant prostate cancer, apalutamide significantly improved health-related quality of life (HRQoL) compared to placebo, with patients maintaining better scores over time.

Patients receiving apalutamide experienced minimal side effects and reported no worsening of fatigue, while those on placebo showed a decline in quality of life after about one year, highlighting the efficacy and tolerability of apalutamide in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life at the SPARTAN Final Analysis of Apalutamide for Nonmetastatic Castration-resistant Prostate Cancer Patients Receiving Androgen Deprivation Therapy. Oudard, S., Hadaschik, B., Saad, F., et al.[2022]

In a study involving 249 men with metastatic castrate-resistant prostate cancer, patient preference between darolutamide and enzalutamide was balanced, with no significant preference for either treatment (p = 0.92).

Darolutamide was associated with less fatigue and a moderate improvement in episodic memory compared to enzalutamide, suggesting it may offer a better quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Open-label, Cross-over Phase 2 Trial of Darolutamide and Enzalutamide in Men with Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer: Patient Preference and Cognitive Function in ODENZA. Colomba, E., Jonas, SF., Eymard, JC., et al.[2023]

Enzalutamide significantly improved radiographic progression-free survival (rPFS) in men with chemotherapy-naïve metastatic castration-resistant prostate cancer across various disease subgroups, including nonvisceral and visceral disease, as well as low- and high-volume bone disease.

The treatment was well tolerated, showing clinically significant benefits in overall survival (OS) for most subgroups, although the results were less definitive for patients with visceral disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer. Evans, CP., Higano, CS., Keane, T., et al.[2022]

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]

Apalutamide is an oral androgen receptor inhibitor that effectively blocks androgen effects, and it received its first global approval in February 2018 for treating non-metastatic castration-resistant prostate cancer (nmCRPC).

Currently, apalutamide is being tested in phase III trials for various prostate cancer stages, including metastatic castration-resistant prostate cancer and high-risk localized prostate cancer, indicating its potential for broader applications in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: First Global Approval. Al-Salama, ZT.[2019]

In a phase III study (TITAN) involving men with metastatic castration-sensitive prostate cancer, adding apalutamide to androgen deprivation therapy significantly improved median radiographic progression-free survival and overall survival.

Apalutamide was found to maintain health-related quality of life and had a safety profile similar to that of placebo when combined with androgen deprivation therapy, expanding treatment options for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. Hoy, SM.[2021]

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

Darolutamide is a potent androgen receptor antagonist with strong efficacy in prostate cancer models. [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life at the SPARTAN Final Analysis of Apalutamide for Nonmetastatic Castration-resistant Prostate Cancer Patients Receiving Androgen Deprivation Therapy. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

A Randomized, Open-label, Cross-over Phase 2 Trial of Darolutamide and Enzalutamide in Men with Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer: Patient Preference and Cognitive Function in ODENZA. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer. [2022]

6. France pubmed.ncbi.nlm.nih.gov

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

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

Apalutamide: First Global Approval. [2019]

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

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. [2021]

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

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