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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether early hormonal therapy in prostate cancer treatment can increase levels of Prostate-Specific Membrane Antigen (PSMA), visible on PET/CT scans. Participants will receive one of three standard hormonal treatments: apalutamide [Erleada], darolutamide [Nubeqa], or enzalutamide [Xtandi]. The trial targets individuals whose prostate cancer has returned after initial treatments like surgery or radiation and who have rising PSA levels, a potential marker of cancer recurrence. This study suits individuals with testosterone levels over 100 ng/dL who do not require more intense treatments at this time. Participants will be involved for about four weeks. As an Early Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants a chance to contribute to groundbreaking research.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that certain medications, such as apalutamide, darolutamide, and enzalutamide, have undergone safety testing for prostate cancer treatment. Studies indicate that darolutamide may cause fewer side effects, like falls, fractures, and rashes, compared to apalutamide, suggesting it might be easier for some patients to tolerate.

Apalutamide has helped patients live longer, indicating its effectiveness and general safety. Enzalutamide has proven effective for high-risk prostate cancer patients, particularly when combined with other treatments.

Overall, while each medication has specific safety considerations, they are generally well-tolerated. Participants in studies have managed these treatments well, though side effects can occur. Always consult a healthcare provider to determine the most suitable option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about androgen receptor antagonists like apalutamide, darolutamide, and enzalutamide for prostate cancer because these treatments specifically target the androgen receptors that fuel cancer cells. Unlike some traditional hormone therapies that might have broader effects, these drugs are designed to more precisely block the signals that encourage cancer growth. This targeted approach can potentially lead to fewer side effects and more effective management of the cancer. Additionally, the use of advanced imaging techniques, such as PSMA PET/CT scans, allows for more accurate monitoring of how well the treatment is working, which can be a game-changer in managing the disease.

What evidence suggests that androgen receptor antagonist monotherapy might be an effective treatment for recurrent prostate cancer?

Research shows that certain medications, such as apalutamide, darolutamide, and enzalutamide, hold promise for treating prostate cancer. In this trial, participants will receive one of these androgen receptor antagonists as monotherapy. Studies have found that apalutamide reduces the risk of death by 23% compared to enzalutamide over two years. Darolutamide is effective, with real-world evidence indicating it has few side effects and is safe. Enzalutamide has delayed disease progression better than some other treatments. Overall, these therapies help patients with prostate cancer live longer and slow cancer growth. ^{2 6 7 8 9}

Who Is on the Research Team?

David J. Einstein, MD

Principal Investigator

Beth Israel Deaconess Medical Center

Are You a Good Fit for This Trial?

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

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

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.

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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]

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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12182483/

Overall Survival with Apalutamide Versus Enzalutamide in ... At 24 months post index, there was a statistically significant 23% reduction in the risk of mortality among patients who initiated apalutamide ...

2. jnj.com jnj.com/media-center/press-releases/erleada-apalutamide-demonstrates-statistically-significant-and-clinically-meaningful-improvement-in-overall-survival-compared-to-enzalutamide-in-patients-with-metastatic-castration-sensitive-prostate-cancer

ERLEADA® (apalutamide) demonstrates statistically ... Largest head-to-head real-world study in mCSPC demonstrated that ERLEADA® reduced risk of death by 23 percent at 24 months compared to ...

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

Real world outcomes of darolutamide efficacy and safety in ... Adverse events led to dose reductions in 4.5% (n=6) of nmHSPC and 1.8% (n=1) of mHSPC patients. Surgical data for 51.1% (n=68) of nmHSPC ...

4. nature.com nature.com/articles/s41391-024-00929-6

Survival outcomes of apalutamide as a starting treatment Starting treatment with APA + ADT was associated with a significantly reduced risk of death compared with ENZ + ADT (aHR, 95%CI) (0.66, 0.51– ...

5. targetedonc.com targetedonc.com/view/comparing-enzalutamide-and-darolutamide-for-prostate-cancer

Comparing Enzalutamide and Darolutamide for Prostate ... A statistical analysis (MAIC) of the ARCHES and ARANOTE studies suggests enzalutamide is more effective at delaying disease progression.

6. urotoday.com urotoday.com/conference-highlights/asco-2020/asco-2020-prostate-cancer/121906-asco-2020-safety-outcomes-of-darolutamide-versus-apalutamide-and-enzalutamide-in-nmcrpc-matching-adjusted-indirect-comparisons.html

Safety Outcomes of Darolutamide Versus Apalutamide and ... Darolutamide had a statistically significant lower risk of falls, fracture, and rash compared to apalutamide; Darolutamide had a lower risk of ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2303974

Improved Outcomes with Enzalutamide in Biochemically ... In patients with prostate cancer with high-risk biochemical recurrence, enzalutamide plus leuprolide was superior to leuprolide alone with ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.5561

Safety outcomes of darolutamide versus apalutamide and ... Safety outcomes of darolutamide versus apalutamide and enzalutamide in nonmetastatic castration-resistant prostate cancer (nmCRPC): Matching- ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12504157/

Comparative effectiveness and safety of enzalutamide ... The median overall survival of pre-docetaxel abiraterone and enzalutamide was 36.1 and 39.9 months, respectively. In contrast, the median ...