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

7 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well apalutamide and abiraterone acetate work in treating participants with castration resistant prostate cancer that has spread to other places in the body (metastatic). Abiraterone acetate and apalutamide may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunosuppressive therapy, such as prednisone, is used to decrease the body's immune response and may improve bone marrow function. Giving apalutamide, abiraterone acetate, and prednisone may work better in treating participants with castration resistant prostate cancer.

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.

What data supports the effectiveness of the drug combination of Apalutamide, Abiraterone, and Prednisone for prostate cancer?

Research shows that Abiraterone acetate combined with Prednisone significantly improves survival and delays disease progression in patients with metastatic prostate cancer. This suggests that the combination with Apalutamide, which is also used for prostate cancer, may enhance these benefits. ^{1 2 3 4 5}

Is the combination of Apalutamide, Abiraterone, and Prednisone safe for humans?

Abiraterone acetate, when combined with prednisone, is generally considered safe for treating metastatic prostate cancer, though it can cause side effects like low potassium levels, high blood pressure, fluid retention, and liver issues. These side effects are usually manageable, and the treatment is well-tolerated by most patients. ^{1 4 6 7 8}

How is the drug combination of Apalutamide, Abiraterone, and Prednisone unique for prostate cancer treatment?

This drug combination is unique because it combines Apalutamide, which blocks signals that help cancer cells grow, with Abiraterone, which stops the body from making certain hormones that fuel cancer, and Prednisone, which helps manage side effects. This multi-faceted approach targets prostate cancer from different angles, potentially improving outcomes compared to using these drugs separately. ^{1 3 4 9 10}

Research Team

Bagi Jana, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

Willing and able to give informed consent

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

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

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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 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]

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]

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 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]

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 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]

References

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

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

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

Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. [2023]

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

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. [2022]

4. 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]

5. England 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. [2022]

6. United States 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. [2018]

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

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

8. England pubmed.ncbi.nlm.nih.gov

Liver tests increase on abiraterone acetate in men with metastatic prostate cancer: Natural history, management and outcome. [2020]

9. England 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. [2021]

10. United States 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. [2022]