Abiraterone/Enzalutamide/Apalutamide for Prostate Cancer

Overseen By Ta-Chueh Rosenberg

Age: Any Age

Sex: Male

Trial Phase: Phase 2

Sponsor: James J. Peters Veterans Affairs Medical Center

Must be taking: Androgen deprivation therapy

Must not be taking: Cytotoxic chemotherapy, Androgen inhibitors

Disqualifiers: Seizure history, Recent DVT/PE, 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: 2 years

200 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators have used national VHA data to demonstrate real-world efficacy of abiraterone and enzalutamide in Veterans with mCRPC. In the real-world that is the VHA, the investigators have successfully estimated g values that accurately predict OS and the use of this metric in other settings should now be explored. In the egalitarian system that is the VHA the treatment of prostate cancer is excellent, uniform across the US and indifferent to race. The choices made are clearly personalized, given not all men received all therapies and that younger Veterans were treated more aggressively. But with survivals that rival those in registration trials that enroll optimally fit individuals usually not encumbered by the co-morbidities that afflict many Veterans, the outcomes are testimony to the fact that for this common malady of older Veterans with whom VA physicians have broad experience the care administered is unsurpassed. Importantly this care at least as regards Veterans with mCRPC demonstrates that given equal access to health care, African Americans with prostate cancer fared as well if not better than Caucasians and importantly had better outcomes with abiraterone, an observation needing further exploration as these therapies move up front.

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

The trial requires that you stop certain hormonal or biologic therapies for prostate cancer at least 4 weeks before joining. If you're on bisphosphonates or denosumab, your dose must be stable for at least 4 weeks before starting the trial.

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

Research shows that Abiraterone and Enzalutamide improve survival in patients with metastatic prostate cancer, especially when used with androgen deprivation therapy (a treatment that lowers male hormones). These drugs are effective in treating prostate cancer that has spread and is resistant to other treatments. ^{1 2 3 4 5}

Is Abiraterone/Enzalutamide/Apalutamide safe for humans?

Abiraterone and enzalutamide, used for advanced prostate cancer, have been associated with risks of metabolic (related to the body's chemical processes) and cardiovascular (heart-related) adverse events. These treatments are generally used with caution, and their safety profiles have been studied in real-world settings. ^{5 6 7 8 9}

What makes the combination of Abiraterone, Enzalutamide, and Apalutamide unique for prostate cancer treatment?

This combination is unique because it targets the androgen receptor (a protein that helps prostate cancer cells grow) in multiple ways, potentially improving survival for patients with metastatic prostate cancer when added to standard hormone therapy. ^{1 4 5 10 11}

Eligibility Criteria

This trial is for Veterans with advanced prostate cancer who are at least 18 years old, can consent to the study, have a good performance status (able to carry out daily activities), and haven't received certain other treatments. They should be on hormone therapy but not previously treated with abiraterone, enzalutamide, or apalutamide.

Inclusion Criteria

Predicted life expectancy of >12 months

I am undergoing or will undergo hormone therapy for my cancer.

Laboratory tests meeting minimum safety requirements for hepatic, renal, and hematological parameters

Exclusion Criteria

I have a specific type of cancer or condition.

I have had a blood clot in my leg or lung in the last 3 months.

I have a history of seizures or conditions that could lead to seizures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive YONSA® (abiraterone acetate), enzalutamide, or apalutamide as first-line therapy

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Abiraterone acetate
• Apalutamide
• Enzalutamide

Trial Overview The trial is testing three medications: Enzalutamide, Apalutamide, and Abiraterone acetate in veterans with castrate-sensitive prostate cancer. It aims to find which drug works best for improving survival without disease progression.

Participant Groups

Group I: Abiraterone Acetate Active Control 1 Intervention

Group II: Standard of Care Active Control 2 Interventions

Abiraterone acetate is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer

Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer
• High-risk metastatic hormone-sensitive prostate cancer

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer

Approved in Japan as Zytiga for:

• Metastatic castration-resistant prostate cancer

Who Is Running the Clinical Trial?

James J. Peters Veterans Affairs Medical Center

Lead Sponsor

Trials

59

Recruited

2,900+

Findings from Research

In a study of 80 patients with metastatic castration-resistant prostate cancer, a shorter time to castration resistance during primary androgen deprivation therapy (ADT) was linked to poorer progression-free survival (PFS) and overall survival after starting treatment with abiraterone or enzalutamide.

Despite the association, the time to castration resistance was not an independent predictor of survival or prostate-specific antigen (PSA) response when analyzed with other factors, suggesting that while it may indicate initial treatment outcomes, it does not determine the effectiveness of subsequent AR-targeting therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Time to Castration Resistance on Outcomes With Abiraterone and Enzalutamide in Metastatic Prostate Cancer. Hung, J., Taylor, AR., Divine, GW., et al.[2021]

In a study of 61 men with metastatic, castration-resistant prostate cancer who had previously received docetaxel and abiraterone acetate, enzalutamide showed modest clinical activity, with 21% of patients experiencing a significant PSA decline of 50% or more.

The median overall survival for patients treated with enzalutamide was 31.6 weeks, and the treatment was generally well tolerated, although fatigue and musculoskeletal pain were common side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical activity and tolerability of enzalutamide (MDV3100) in patients with metastatic, castration-resistant prostate cancer who progress after docetaxel and abiraterone treatment. Badrising, S., van der Noort, V., van Oort, IM., et al.[2022]

In a study of 104 patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate, the median overall survival was 16.4 months, highlighting the drug's effectiveness in this patient population.

Key prognostic factors for overall survival included early PSA response (greater than 30% decline at four weeks) and ECOG performance status, suggesting that these metrics can help identify patients who are more likely to benefit from abiraterone acetate treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PSA Kinetics as Prognostic Markers of Overall Survival in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone Acetate. España, S., Ochoa de Olza, M., Sala, N., et al.[2022]

In a network meta-analysis of four trials involving treatments for castration-resistant, docetaxel-resistant metastatic prostate cancer, no significant differences in overall survival were found among abiraterone acetate, enzalutamide, cabazitaxel, and Radium-223.

However, enzalutamide showed a significant advantage over the other treatments in delaying PSA progression, suggesting it may be more effective in managing disease progression despite similar overall survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Metastatic, Castration-resistant, Docetaxel-resistant Prostate Cancer: A Systematic Review of Literature With a Network Meta-analysis of Randomized Clinical Trials. Tassinari, D., Cherubini, C., Roudnas, B., et al.[2021]

In a study involving 1919 patients with metastatic prostate cancer, the addition of abiraterone acetate to standard androgen deprivation therapy significantly improved overall survival, with a median survival of 76.6 months compared to 45.7 months for standard care alone.

Combining both abiraterone and enzalutamide did not provide additional survival benefits over abiraterone alone, and it was associated with higher rates of severe side effects, suggesting that this combination should be avoided in long-term treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. Attard, G., Murphy, L., Clarke, NW., et al.[2023]

In a study of 137 chemo-naïve patients with metastatic castration-resistant prostate cancer, Enzalutamide (EZ) showed a significantly higher PSA response rate compared to Abiraterone (AA) in the first line of treatment (95.9% vs 67%).

Both AA and EZ had comparable toxicity rates and progression-free survival (PFS) outcomes, indicating that both treatments are effective and well-tolerated options for managing mCRPC without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. Ferriero, M., Mastroianni, R., De Nunzio, C., et al.[2021]

Oral abiraterone acetate (Zytiga®) significantly improves overall survival and progression-free survival in patients with metastatic castration-resistant prostate cancer (CRPC) when used with prednisone, compared to a placebo.

The treatment is specifically effective for patients who have already undergone docetaxel-containing chemotherapy, highlighting its role as a subsequent therapy in advanced prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. Scott, LJ., Yang, LPH., Lyseng-Williamson, KA.[2021]

Men with advanced prostate cancer taking abiraterone have a significantly higher risk of major metabolic or cardiovascular adverse events compared to those not on the medication, with a hazard ratio of 1.77.

Enzalutamide also increases the risk of major adverse events, but to a lesser extent (hazard ratio of 1.22), and does not significantly increase the risk of minor adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Metabolic and Cardiovascular Adverse Events With Abiraterone or Enzalutamide Among Men With Advanced Prostate Cancer. Lai, LY., Oerline, MK., Caram, MEV., et al.[2023]

A study involving 32 healthy male subjects demonstrated that the test product (abiraterone acetate tablet) is bioequivalent to the reference product ZYTIGA® in terms of pharmacokinetics, with both products showing similar maximum concentration (Cmax) and area under the curve (AUC) values within the acceptable range.

The research confirmed significant intra-subject variability in the pharmacokinetics of abiraterone, indicating that individual responses to the drug can vary widely, which is important for clinicians to consider when prescribing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. Wang, C., Hu, C., Gao, D., et al.[2022]

In a study of 3,398 patients with metastatic castration-resistant prostate cancer, those initiated on abiraterone acetate (AA) had a significantly longer duration of treatment compared to those initiated on enzalutamide (ENZ), with a median duration of 18.3 months for AA versus 14.2 months for ENZ.

Patients on AA also experienced fewer treatment discontinuations at various time points, indicating that AA may provide a more sustained treatment option for managing prostate cancer compared to ENZ.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duration of Treatment in Prostate Cancer Patients Treated with Abiraterone Acetate or Enzalutamide. Pilon, D., Behl, AS., Ellis, LA., et al.[2023]

The use of abiraterone and enzalutamide, oral therapies for metastatic castration-resistant prostate cancer, has significantly increased among urologists from 2013 to 2016, with abiraterone prescriptions rising from 71,423 to 100,371 and enzalutamide from 29,572 to 100,980.

The number of urologists prescribing these medications in moderate to high volumes grew substantially, indicating a shift in treatment practices, with 301 urologists prescribing abiraterone and 671 prescribing enzalutamide by 2016, primarily within single-specialty groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoption of Abiraterone and Enzalutamide by Urologists. Caram, MEV., Kaufman, SR., Modi, PK., et al.[2021]

References

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

The Effect of Time to Castration Resistance on Outcomes With Abiraterone and Enzalutamide in Metastatic Prostate Cancer. [2021]

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

Clinical activity and tolerability of enzalutamide (MDV3100) in patients with metastatic, castration-resistant prostate cancer who progress after docetaxel and abiraterone treatment. [2022]

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

PSA Kinetics as Prognostic Markers of Overall Survival in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone Acetate. [2022]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Treatment of Metastatic, Castration-resistant, Docetaxel-resistant Prostate Cancer: A Systematic Review of Literature With a Network Meta-analysis of Randomized Clinical Trials. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. [2021]

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

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. [2021]

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

Risk of Metabolic and Cardiovascular Adverse Events With Abiraterone or Enzalutamide Among Men With Advanced Prostate Cancer. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. [2022]

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

Duration of Treatment in Prostate Cancer Patients Treated with Abiraterone Acetate or Enzalutamide. [2023]

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

Adoption of Abiraterone and Enzalutamide by Urologists. [2021]