Apalutamide + Abiraterone + Prednisone for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: GnRH analogues

Must not be taking: Antipsychotics, Antidepressants, Insulin, others

Disqualifiers: Brain metastases, Seizure history, Cardiovascular disease, 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: 28-day cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three medications—apalutamide, abiraterone acetate, and prednisone—to evaluate their effectiveness against prostate cancer that has spread and resists standard hormone therapy. The goal is to determine if these drugs can more effectively halt cancer cell growth by blocking certain enzymes and enhancing bone marrow function. Men with metastatic prostate cancer unresponsive to hormone therapy, who are already receiving hormone-blocking treatment, might be suitable candidates for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as androgen receptor antagonists, 5-alpha reductase inhibitors, estrogens, chemotherapy, or biologic therapy, at least 4 weeks before starting the trial. Additionally, you cannot use medications known to lower the seizure threshold from 30 days before enrollment through the end of the study.

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

Studies have shown that the combination of apalutamide, abiraterone acetate, and prednisone is generally safe and well-tolerated for treating prostate cancer. Research indicates that many patients using this treatment continue without major issues. For example, one study found that a large number of patients successfully stayed on the treatment plan.

However, like all medications, side effects can occur. These may include fatigue, skin rashes, and high blood pressure. It's important to know that these side effects are often manageable. Larger studies have shown that this treatment can improve outcomes for patients with prostate cancer, potentially preventing the disease from worsening.

Overall, while side effects can happen, the treatment is considered safe for many patients. Prospective trial participants should discuss any concerns with a doctor, who can provide more details on what to expect and how to handle any possible side effects. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for prostate cancer?

Researchers are excited about the combination of apalutamide, abiraterone acetate, and prednisone for prostate cancer because it promises a more comprehensive approach to treatment. Unlike standard therapies that often target either androgen production or activity, this combination tackles both. Apalutamide blocks the androgen receptor, preventing cancer cells from using androgens to grow, while abiraterone acetate inhibits the production of androgens. This dual mechanism, coupled with prednisone to manage side effects, could lead to more effective management of prostate cancer progression.

What evidence suggests that this treatment might be an effective treatment for prostate cancer?

Research has shown that a combination of three drugs—apalutamide, abiraterone acetate, and prednisone—can be promising for treating advanced prostate cancer that no longer responds to standard hormone therapy. In this trial, participants will receive this combination treatment. Studies have found that adding apalutamide to abiraterone and prednisone improves results compared to using just abiraterone and prednisone, leading to more positive patient responses. Specifically, one study showed that patients on this treatment had a 26% lower risk of death over two years compared to those taking only abiraterone. Overall, these findings suggest that this combination might be more effective in controlling the spread of prostate cancer. ^{1 4 6 7 8}

Who Is on the Research Team?

Bagi Jana, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Men with metastatic castration resistant prostate cancer, who have low testosterone levels and progressive disease despite ongoing hormone therapy. They must be able to give consent, swallow pills, and agree to use two forms of birth control if sexually active with a woman of childbearing potential. Excluded are those with severe health issues like uncontrolled hypertension or heart problems, recent major surgery, brain metastases, certain blood disorders or allergies to study drugs.

Inclusion Criteria

Estimated life expectancy of >= 6 months

Serum testosterone level =< 50 ng/dL at the screening visit

Serum albumin >= 3.0 g/dL

Exclusion Criteria

Severe, concurrent disease, infection, or co-morbidity that would make the patient inappropriate for enrollment or other medical condition that would make corticosteroid use contraindicated

Abnormal blood counts or levels (ANC, platelet count, hemoglobin, total bilirubin, ALT, AST, creatinine)

I have had cancer other than skin cancer in the past 2 years with a high chance of return.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abiraterone acetate, apalutamide, and prednisone orally once daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 16 months

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone Acetate
• Apalutamide
• Prednisone

Trial Overview The trial is testing the effectiveness of combining apalutamide and abiraterone acetate—drugs that block tumor growth enzymes—with prednisone which suppresses the immune system and may improve bone marrow function in treating metastatic prostate cancer that resists castration treatment.

How Is the Trial Designed?

Group I: Treatment (abiraterone acetate, apalutamide, prednisone) Experimental Treatment 3 Interventions

Participants receive abiraterone acetate PO once daily QD, apalutamide PO QD, and prednisone PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Metastatic high-risk castration-sensitive prostate cancer

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Newly diagnosed high-risk metastatic hormone-sensitive prostate cancer

Approved in Canada as Zytiga for:

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

Approved in Japan as Zytiga for:

• Prostate cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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]

In a study of 25 men with metastatic prostate cancer, liver function test increases were observed while on abiraterone treatment, typically occurring within the first two months of therapy.

Despite these increases, liver toxicity was generally mild, with most patients experiencing a return to normal liver function either spontaneously or after dose adjustments, indicating that abiraterone is relatively safe regarding liver health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver tests increase on abiraterone acetate in men with metastatic prostate cancer: Natural history, management and outcome. Colomba, E., Marret, G., Baciarello, G., et al.[2020]

Abiraterone acetate significantly improves overall survival and radiographic progression-free survival in men with metastatic castration-resistant prostate cancer (CRPC) when combined with prednisone, based on results from a multinational phase III study involving men who had previously received docetaxel.

The treatment is generally well-tolerated, although it can cause side effects like hypokalaemia and hypertension; however, serious adverse events were relatively low in the phase III studies, indicating it is a viable option for managing metastatic CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a review of its use in patients with metastatic castration-resistant prostate cancer. Hoy, SM.[2021]

In a clinical trial involving 164 men with metastatic castration-resistant prostate cancer, abiraterone acetate combined with prednisone (5 mg twice daily) or dexamethasone (0.5 mg once daily) effectively minimized mineralocorticoid excess, which is important for patient safety.

While abiraterone with dexamethasone showed promising efficacy, it was also linked to adverse metabolic effects, such as increased insulin resistance and decreased bone mineral density, highlighting the need for careful monitoring of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the Safety of Glucocorticoid Regimens in Combination With Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer: A Randomized, Open-label Phase 2 Study. Attard, G., Merseburger, AS., Arlt, W., et al.[2022]

Abiraterone acetate, in combination with prednisone, received full FDA approval for treating metastatic castration-resistant prostate cancer (mCRPC) based on the COU-AA-302 trial, which involved 1,088 patients and showed a significant improvement in radiographic progression-free survival (rPFS) compared to placebo (8.3 months vs. not reached).

The trial also indicated a favorable trend in overall survival (OS) for patients receiving abiraterone acetate, although it did not reach statistical significance, confirming the drug's efficacy and safety profile consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer: U.S. Food and Drug Administration drug approval summary. Kluetz, PG., Ning, YM., Maher, VE., et al.[2018]

In a study involving 1917 men with locally advanced or metastatic prostate cancer, the combination of abiraterone acetate and prednisolone with androgen-deprivation therapy (ADT) significantly improved overall survival compared to ADT alone, with a hazard ratio of 0.63, indicating a 37% reduction in the risk of death.

The combination therapy also resulted in a much lower rate of treatment failure, with a hazard ratio of 0.29, meaning patients were less likely to experience disease progression compared to those receiving only ADT, although it was associated with a higher incidence of grade 3 to 5 adverse events (47% vs. 33%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. James, ND., de Bono, JS., Spears, MR., et al.[2023]

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]

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]

In a phase 3 trial involving 1199 patients, the addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly improved overall survival, with a median survival not reached in the abiraterone group compared to 34.7 months in the placebo group.

The study also showed that patients receiving abiraterone had a median radiographic progression-free survival of 33.0 months, compared to 14.8 months in the placebo group, indicating a strong benefit in delaying disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. Fizazi, K., Tran, N., Fein, L., et al.[2022]

In a study of 1199 men with metastatic castration-sensitive prostate cancer, treatment with abiraterone acetate plus prednisone (AA+P) significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) compared to placebo, particularly in patients with lung metastases.

Patients with visceral metastases (VM) who received AA+P had a median OS of 55.4 months versus 33.0 months for those on placebo, and a median rPFS of 30.7 months compared to 18.3 months, indicating that AA+P is an effective treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of abiraterone acetate plus prednisone in patients with castration-sensitive prostate cancer and visceral metastases over four years of follow-up: A post-hoc exploratory analysis of the LATITUDE study. Baciarello, G., Özgüroğlu, M., Mundle, S., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9377412/

Apalutamide plus abiraterone acetate and prednisone in ... The addition of apalutamide to abiraterone-prednisone versus abiraterone-prednisone alone resulted in a significantly higher rate of confirmed ≥ ...

2. targetedonc.com targetedonc.com/view/abiraterone-prednisone-apalutamide-improves-prostate-cancer-outcomes-leaves-hrqol-unaffected

Abiraterone, Prednisone, Apalutamide Improves Prostate ... Oncological outcomes improved with the addition of abiraterone acetate (Zytiga) plus prednisone (AAP) and apalutamide (Erleada) after radical prostatectomy.

3. jnjmedicalconnect.com jnjmedicalconnect.com/products/erleada/medical-content/erleada-comparison-of-erleada-with-zytiga

Comparison of ERLEADA with ZYTIGA By 24 months postindex, patients initiated on ERLEADA had a statistically significant reduction of 26% in the risk of death when compared with patients ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.367

Real-world discontinuation and efficacy data of abiraterone ... Our analysis revealed a notably high rate of early discontinuation of AAP in the real-world setting in patients treated for their localized prostate cancer.

5. becarispublishing.com becarispublishing.com/doi/10.57264/cer-2025-0023

a head-to-head analysis of real-world patients in the USA The results of this study show that compared with abiraterone acetate, initial treatment with apalutamide resulted in better real-world survival ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5543693/

Safety and Antitumor Activity of Apalutamide (ARN-509) in ... Apalutamide was safe, well tolerated, and demonstrated clinical activity in mCRPC with 80% of AAP-naïve and 43% of post-AAP patients remaining on treatment for ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02257736

Study Details | NCT02257736 | An Efficacy and Safety ... The purpose of this study is to compare the radiographic progression-free survival (rPFS) of apalutamide in combination with abiraterone acetate (AA) plus ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1704174

Abiraterone plus Prednisone in Metastatic, Castration- ... The median length of radiographic progression-free survival was 33.0 months in the abiraterone group and 14.8 months in the placebo group ( ...