Abiraterone + Prednisone for Prostate Cancer

(APRE Trial)

Recruiting at 2 trial locations

Overseen By Martha Mims, MD, PhD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Martha Mims

Must be taking: Abiraterone, Prednisone

Must not be taking: Ketoconazole, Aminoglutethimide, Enzalutamide

Disqualifiers: Brain metastases, Heart failure, 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: Up to 3 years

130 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators are conducting this study with men that have prostate cancer and are getting standard of care treatment with the drugs abiraterone acetate and prednisone. The study will follow men with prostate cancer from initiation of participation in the study and for up to 10 years. The reason for the study is that researchers think that there may be a connection between the race and ethnicity of men with prostate cancer and how well the standard treatments work for the participants.

Will I have to stop taking my current medications?

The trial does not require a washout period for antiandrogens or five alpha reductase inhibitors, so you may not need to stop these medications. However, you cannot take ketoconazole, aminoglutethimide, or enzalutamide during the trial.

What data supports the effectiveness of the drug Abiraterone Acetate plus Prednisone for prostate cancer?

Research shows that Abiraterone Acetate combined with Prednisone significantly improves survival and delays disease progression in patients with metastatic castration-resistant prostate cancer, especially those who have not received chemotherapy before. ^{1 2 3 4 5}

Is Abiraterone + Prednisone safe for humans?

Abiraterone acetate combined with prednisone is generally considered safe for treating prostate cancer, but it can cause side effects like low potassium levels, high blood pressure, fluid retention, and liver issues. These side effects were relatively low in frequency in clinical studies. ^{1 2 6 7 8}

How is the drug Abiraterone Acetate with Prednisone unique for prostate cancer?

Abiraterone Acetate with Prednisone is unique because it blocks the production of androgens (male hormones) that fuel prostate cancer growth, and is taken orally, making it more convenient than some other treatments. It is particularly effective for patients with metastatic castration-resistant prostate cancer, significantly improving survival and delaying disease progression compared to standard treatments. ^{1 2 4 6 9}

Research Team

Martha Mims, MD, PhD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

Men with metastatic hormone naive prostate cancer who have not received certain prior treatments like ketoconazole or chemotherapy for metastasis. They must be over 18, have adequate organ function, and a Zubrod performance status of 0-2 (3 if due to bone pain). Prior surgery is okay after recovery, and they can't have severe heart issues or known brain metastases.

Inclusion Criteria

I had surgery over 2 weeks ago and have recovered from major side effects.

Patients must have a PSA ≥ 10 ng/mL obtained within 90 days prior to registration.

I am taking or plan to take bone-strengthening drugs that don't affect PSA levels.

Exclusion Criteria

I do not have brain metastases.

I haven't had chemotherapy for metastatic prostate cancer but may have had it earlier with a curative goal.

I am not allergic to abiraterone or LHRH agonists.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abiraterone acetate and prednisone as per standard of care until disease progression

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 months

Long-term follow-up

Participants are followed for up to 10 years to assess long-term outcomes

Up to 10 years

Treatment Details

Interventions

• Abiraterone Acetate
• Prednisone

Trial Overview The study examines the effectiveness of standard care treatment with abiraterone acetate and prednisone in men with prostate cancer across different races/ethnicities. Participants will be followed for up to 10 years to see how well these treatments work.

Participant Groups

Group I: Abiraterone acetate + prednisone Experimental Treatment 2 Interventions

All subjects will receive abiraterone acetate and prednisone, as per standard of care. Abiraterone acetate will be administered orally as 1000 mg once daily along with 5 mg of oral prednisone twice per day. Subjects will continue to take abiraterone acetate and prednisone until confirmed disease progression.

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?

Martha Mims

Lead Sponsor

Trials

1

Recruited

130+

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 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]

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 phase 3 trial with 1088 patients, abiraterone acetate plus prednisone significantly improved overall survival compared to placebo plus prednisone, with a median survival of 34.7 months versus 30.3 months, indicating its efficacy in treating chemotherapy-naive castration-resistant prostate cancer.

The treatment was associated with a manageable safety profile, although there were some increased risks of grade 3-4 adverse events, such as cardiac disorders and elevated liver enzymes, suggesting that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Ryan, CJ., Smith, MR., Fizazi, K., 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 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 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 254 metastatic castration-resistant prostate cancer patients treated with abiraterone acetate plus prednisone (AA+P) over a median follow-up of 67.1 weeks, patient-reported outcomes (PROs) showed no significant decline in quality of life or cognitive function, indicating that the treatment is well-tolerated.

The study also reported a 66.4% response rate in prostate-specific antigen (PSA) levels, demonstrating the efficacy of AA+P in managing this patient population while maintaining their overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world evidence in patient-reported outcomes (PROs) of metastatic castrate-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate + prednisone (AA+P) across Canada: Final results of COSMiC. Gotto, G., Drachenberg, DE., Chin, J., et al.[2020]

In a study of 1088 patients with metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate combined with prednisone significantly improved radiographic progression-free survival (rPFS) compared to prednisone alone, with a median rPFS of 16.5 months versus 8.2 months.

Abiraterone acetate also showed a trend towards improved overall survival (OS) with a median of 35.3 months compared to 30.1 months for prednisone, indicating a potential benefit in prolonging life, while maintaining a favorable safety profile over long-term treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302). Rathkopf, DE., Smith, MR., de Bono, JS., 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 plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. [2022]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. [2022]

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. 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]

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. Canada pubmed.ncbi.nlm.nih.gov

Real-world evidence in patient-reported outcomes (PROs) of metastatic castrate-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate + prednisone (AA+P) across Canada: Final results of COSMiC. [2020]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302). [2022]