Enzalutamide + Abiraterone + Prednisone for Prostate Cancer

Recruiting at 179 trial locations

Overseen By Astellas Pharma Global Development

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Astellas Pharma Global Development, Inc.

Must be taking: Enzalutamide

Must not be taking: New systemic therapy

Disqualifiers: Cancer progression, Investigator trials, 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

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

Compensation: Varies

Number of Visits: 2

Duration: 24 weeks

900 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the long-term safety of enzalutamide for individuals with prostate cancer. It targets those who have participated in a previous study with enzalutamide and continue to benefit from it. Participants may also receive additional treatments, such as leuprolide acetate or a combination of abiraterone (a hormone therapy) and prednisone (a corticosteroid), alongside enzalutamide. Ideal participants are those currently benefiting from enzalutamide in a previous study and can maintain the treatment routine. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must continue with the enzalutamide treatment you were receiving in the prior study, and any changes to your regimen require approval from a medical monitor.

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

Research has shown that enzalutamide is generally well-tolerated by patients. In one study with 2,275 participants, enzalutamide reduced the risk of death by 33% compared to a control group, suggesting it is both effective and safe for many people. Another study found that when enzalutamide was combined with leuprolide, nearly 79% of patients survived over eight years, indicating it is safe for long-term use.

However, results are mixed when enzalutamide is combined with abiraterone and prednisone. One study found that enzalutamide and abiraterone have similar long-term safety when used separately, but another study advised against using them together for some patients starting long-term hormone therapy. This suggests that while each drug may be safe on its own, combining them could be risky for some people.

Overall, enzalutamide alone appears to have a strong safety record, but adding other drugs like abiraterone and prednisone should be carefully considered. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine enzalutamide with other drugs like abiraterone acetate and prednisone to tackle prostate cancer from multiple angles. Enzalutamide works by blocking the androgen receptor, which plays a crucial role in the growth of prostate cancer cells. Adding abiraterone, which lowers androgen levels, and prednisone, which helps manage side effects, creates a powerful combination that could be more effective than current standard treatments. This approach might offer a more comprehensive attack on the cancer, potentially improving patient outcomes and providing new hope for those with advanced disease.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that enzalutamide improves survival rates for prostate cancer patients. One study found that men taking enzalutamide had a 61% lower risk of cancer progression compared to those not taking it. In this trial, some participants will receive enzalutamide alone, while others will receive enzalutamide with leuprolide, which has significantly increased overall survival compared to leuprolide alone.

Another group in this trial will receive a combination of enzalutamide, abiraterone, and prednisone. Research indicates that survival outcomes for this combination are similar to those for enzalutamide alone. While the combination does not offer much additional benefit, it remains a viable option with comparable effectiveness. Overall, enzalutamide has demonstrated strong potential in treating prostate cancer, whether used alone or with other medications. ^{2 3 4 6 7}

Who Is on the Research Team?

Associate Medical Director

Principal Investigator

Astellas Pharma Global Development, Inc.

Are You a Good Fit for This Trial?

This trial is for individuals with prostate cancer who are benefiting from Enzalutamide in a previous Astellas or Medivation study. They must be able to swallow capsules, not join other trials, and use two forms of birth control if applicable. Those whose cancer worsened on Enzalutamide or need new systemic therapies cannot participate.

Inclusion Criteria

I can keep taking the same cancer treatment I was on before, unless my doctor changes it.

I am currently on enzalutamide for breast cancer in an Astellas or Medivation/Pfizer study and it's working for me.

I am not able to have children, or I can and will follow strict birth control measures during the study.

Exclusion Criteria

I need new treatment for my cancer, but not one I've had before.

I need new systemic therapy for my cancer, but not treatments I've had before.

I am currently in a trial and taking enzalutamide.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants continue the treatment regimen from the prior study with enzalutamide, and possibly abiraterone acetate and prednisone, with dose adjustments allowed after medical monitor approval.

24 weeks

1 visit every 24 weeks (in-person), 1 visit every 12 weeks (IP only)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with adverse events and serious adverse events collected.

24 weeks

1 visit every 24 weeks (in-person)

Open-label extension

Participants may continue to receive enzalutamide long-term as they derive clinical benefit.

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone Acetate
• Enzalutamide
• Prednisone

Trial Overview The study aims to collect long-term safety data on the continued use of Enzalutamide, along with abiraterone acetate and prednisone, for those showing clinical benefits from prior studies.

How Is the Trial Designed?

Group I: enzalutamide plus abiraterone acetate and prednisone Experimental Treatment 3 Interventions

Subjects enrolling from study 9785-CL-0011 or MDV3100-10 (PLATO) study may receive abiraterone acetate once daily and prednisone twice daily, in addition to enzalutamide once daily

Group II: enzalutamide Experimental Treatment 1 Intervention

Subjects will receive enzalutamide orally once daily at the same time each day

Group III: Enzalutamide plus leuprolide acetate Experimental Treatment 2 Interventions

Subjects enrolling from study MDV3100-13 (EMBARK) study may receive leuprolide acetate once every 12 weeks in addition to enzalutamide once daily

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

Approved in United States as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in European Union as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Canada as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Japan as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Who Is Running the Clinical Trial?

Astellas Pharma Global Development, Inc.

Lead Sponsor

Trials

204

Recruited

123,000+

Tadaaki Taniguchi

Astellas Pharma Global Development, Inc.

Chief Medical Officer

M.D., Ph.D.

Naoki Okamura

Astellas Pharma Global Development, Inc.

Chief Executive Officer

Not available

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

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]

Enzalutamide is an effective androgen receptor inhibitor that improves overall survival in patients with metastatic castration-resistant prostate cancer, showing a 4.8-month survival benefit in those previously treated with docetaxel, as demonstrated in the Phase III AFFIRM trial.

The FDA has expanded enzalutamide's approval to include first-line treatment for metastatic castration-resistant prostate cancer in patients who have not yet received chemotherapy, and it is associated with an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide for patients with metastatic castration-resistant prostate cancer. Ramadan, WH., Kabbara, WK., Al Basiouni Al Masri, HS.[2020]

A 76-year-old man developed severe thrombocytopenia after 13 days of enzalutamide treatment for castration-resistant prostate cancer, indicating that this side effect can occur early in therapy.

After discontinuing enzalutamide, the patient's platelet count recovered, and he was able to restart the medication without recurrence of thrombocytopenia; however, he later experienced a seizure, suggesting that enzalutamide may also be associated with neurological adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. Murata, M., Takizawa, I., Maruyama, R., et al.[2022]

In a study of 133 patients with non-metastatic castration-resistant prostate cancer, abiraterone acetate (AA) plus prednisone showed comparable overall survival and cancer-specific survival to enzalutamide (Enz) over a median follow-up of 36 months.

However, patients treated with AA plus prednisone had a significantly higher risk of non-cancer-caused death compared to those treated with Enz, suggesting that while both treatments are effective, AA plus prednisone may pose additional safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world survival outcome comparing abiraterone acetate plus prednisone and enzalutamide for nonmetastatic castration-resistant prostate cancer. Tsujino, T., Tokushige, S., Komura, K., 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]

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]

In a study of 143 men with metastatic castration-resistant prostate cancer, those treated with Enzalutamide (ENZ) experienced significantly longer biochemical progression-free survival compared to those treated with Abiraterone acetate plus Prednisone (AA+P), with a hazard ratio of 0.54.

There was no significant difference in overall survival between the two treatment groups, indicating that while ENZ may delay disease progression, it does not necessarily extend overall survival compared to AA+P.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus Prednisone/Prednisolone compared with Enzalutamide in metastatic castration resistant prostate cancer before or after chemotherapy: A retrospective study of real-world data (ACES). Das, P., Taylor, S., Price, J., et al.[2022]

In a study involving 202 patients with metastatic castration-resistant prostate cancer, the sequence of treatment with abiraterone acetate followed by enzalutamide resulted in a longer time to second PSA progression (19.3 months) compared to the reverse sequence (15.2 months), indicating a more effective treatment strategy.

Enzalutamide demonstrated a significantly higher PSA response rate (36%) as a second-line therapy compared to abiraterone (4%), suggesting that enzalutamide is more effective when used after abiraterone in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial. Khalaf, DJ., Annala, M., Taavitsainen, S., et al.[2021]

In a study of 97 chemotherapy-naive patients with metastatic castration-resistant prostate cancer, the order of treatment with abiraterone (AA) and enzalutamide (ENZA) did not significantly affect overall survival or progression-free survival outcomes.

However, there was a notable difference in the PSA response rate during second-line treatment, with ENZA showing a 30% response compared to only 6.4% for AA, suggesting that the sequence of administration may influence treatment effectiveness in later stages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone Followed by Enzalutamide Versus Enzalutamide Followed by Abiraterone in Chemotherapy-naive Patients With Metastatic Castration-resistant Prostate Cancer. Matsubara, N., Yamada, Y., Tabata, KI., et al.[2021]

In a study of 214 patients with metastatic castration-resistant prostate cancer (mCRPC) who had progressed after at least 24 weeks of abiraterone acetate plus prednisone, enzalutamide demonstrated antitumor activity, with a median radiographic progression-free survival of 8.1 months.

Despite some evidence of cross-resistance between abiraterone and enzalutamide, 27% of patients showed a prostate-specific antigen (PSA) response, indicating that enzalutamide can still be effective for certain individuals after prior treatment with abiraterone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumour Activity and Safety of Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer Previously Treated with Abiraterone Acetate Plus Prednisone for ≥24 weeks in Europe. de Bono, JS., Chowdhury, S., Feyerabend, S., et al.[2021]

In a study of 100 patients with metastatic castration-resistant prostate cancer, those treated with enzalutamide (ENZA) reported significantly more fatigue and neurocognitive issues compared to those treated with abiraterone acetate plus prednisone (AA+P).

While both treatments had similar rates of severe adverse events, ENZA was associated with unique neuropsychiatric side effects such as memory impairment and confusion, indicating a need for careful monitoring of cognitive function in patients receiving this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a Real-world Study of Enzalutamide and Abiraterone Acetate With Prednisone Tolerability (REAAcT). Shore, ND., Saltzstein, D., Sieber, P., et al.[2021]

Citations

1. pfizer.com pfizer.com/news/press-release/press-release-detail/astellas-and-pfizers-xtanditm-enzalutamide-shows-long-term

Astellas and Pfizer's XTANDI™ (enzalutamide) Shows ... OS at 96 months was 50% with XTANDI and 40% for NSAA; progression-free survival (PFS) also favored XTANDI over NSAA (HR: 0.49; 95% CI, 0.42-0.57) ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2510310?query=featured_home

Improved Survival with Enzalutamide in Biochemically ... In this trial, enzalutamide plus leuprolide led to significantly longer overall survival than leuprolide alone among patients with castration- ...

3. xtandihcp.com xtandihcp.com/cspc/efficacy

Efficacy CSPC | HCP Site | XTANDI® (enzalutamide) XTANDI (single agent) significantly improved metastasis-free survival vs placebo + GnRH therapy* · Number of events: 63 (17.7%) with XTANDI (single agent) vs 92 ...

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

Comparative effectiveness and safety of enzalutamide ... Effectiveness outcomes included all-cause death, prostate cancer-related death, and treatment failure. Safety outcomes included major adverse CV ...

5. xtandi.com xtandi.com/clinical-trials

Clinical Trial Results | XTANDI® (enzalutamide) Men taking XTANDI had a 61% lower chance of their cancer progressing compared with men not taking XTANDI during the study. Progression was seen in 89 men (15.5 ...

6. pfizer.com pfizer.com/news/press-release/press-release-detail/xtandir-plus-leuprolide-reduced-risk-death-40-vs-leuprolide

XTANDI® Plus Leuprolide Reduced Risk of Death by 40% ... The probability of survival at 8 years was an unprecedented 78.9% with XTANDI plus leuprolide versus 69.5% with leuprolide, in men with ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40660075/

The efficacy and safety of enzalutamide in metastatic ... Results: The data of 2275 patients were analyzed eventually. Enzalutamide reduced the risk of death by 33% compared to the control. Specifically ...