Abiraterone + Prednisone vs Darolutamide for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Mamta Parikh

Must be taking: Androgen deprivation therapy

Must not be taking: Abiraterone, Darolutamide

Disqualifiers: Inability to consent, 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: 1

Duration: 52 weeks

75 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial compares the effects, good and/or bad of abiraterone and prednisone or darolutamide alone in treating patients with prostate cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Androgens (male hormones) can cause the growth of prostate tumor cells. Abiraterone acetate lowers the amount of androgens made by the body. This may help stop the growth of prostate tumor cells that need androgen to grow. Darolutamide blocks the use of androgens by the tumor cells. Prednisone is used to lessen inflammation and lower the body's immune response. Researchers want to compare the side effects of standard of care (SOC) abiraterone and prednisone or darolutamide alone in treating patients with advanced prostate cancer.

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 should discuss your current medications with the trial team to ensure they don't interfere with the study treatments.

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

Research shows that Abiraterone plus Prednisone significantly improves survival and delays disease progression in patients with metastatic castration-resistant prostate cancer, especially those who have previously received chemotherapy. ^{1 2 3 4 5}

Is the combination of Abiraterone and Prednisone safe for treating prostate cancer?

Abiraterone combined with Prednisone is generally considered safe for treating metastatic prostate cancer, but 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 overall safety profile is acceptable for patients with this condition. ^{1 3 4 6 7}

What makes the drug combination of Abiraterone, Prednisone, and Darolutamide unique for prostate cancer?

This drug combination is unique because it combines Abiraterone, which blocks the production of male hormones that fuel prostate cancer, with Prednisone, a steroid that helps manage side effects, and Darolutamide, a newer drug that blocks the effects of male hormones on cancer cells. This combination may offer a more comprehensive approach to treating prostate cancer compared to using these drugs individually. ^{1 4 8 9 10}

Research Team

Mamta Parikh

Principal Investigator

University of California, Davis

Eligibility Criteria

This trial is for men with advanced prostate cancer that has spread beyond the original site. Participants should not have had prior treatment with abiraterone, prednisone, or darolutamide. They must be able to provide tissue samples and willing to follow study procedures.

Inclusion Criteria

Ability to understand and willingness to sign an informed consent form

My advanced prostate cancer is suitable for treatment with specific hormone therapies.

I can take care of myself but may not be able to do active work.

Exclusion Criteria

I have been taking abiraterone or darolutamide for more than 28 days.

Any condition that in the opinion of the investigator would prohibit the understanding or rendering of informed consent or interfere with the participant's safety or compliance while on trial

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive abiraterone and prednisone or darolutamide for 1 year

52 weeks

Regular visits for blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Treatment Details

Interventions

• Abiraterone
• Darolutamide
• Prednisone

Trial Overview The trial compares two treatments: one group receives abiraterone plus prednisone (standard care), while the other gets just darolutamide. The goal is to see which treatment better stops tumor growth by affecting male hormone levels or blocking their use by tumors.

Participant Groups

Group I: Arm II (darolutamide) Experimental Treatment 2 Interventions

Patients receive darolutamide per SOC. Treatment continues for 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples during screening and on study.

Group II: Arm I (abiraterone, prednisone) Experimental Treatment 3 Interventions

Patients receive abiraterone and prednisone per SOC. Treatment continues for 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples during screening and on study.

Abiraterone 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 (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in Japan as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Who Is Running the Clinical Trial?

Mamta Parikh

Lead Sponsor

Trials

7

Recruited

210+

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]

The updated COU-AA-301 study shows that abiraterone combined with prednisone significantly improves survival in patients with metastatic castration-resistant prostate cancer who have previously undergone docetaxel treatment.

This finding supports the continued use of abiraterone in later stages of prostate cancer and highlights its potential benefits compared to other treatments and disease states.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone and its place in the treatment of metastatic CRPC. Sartor, O., Pal, SK.[2021]

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 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 (AAP) combined with prednisone/prednisolone has been recommended for treating metastatic castration-resistant prostate cancer (mCRPC) based on its clinical effectiveness compared to best supportive care, although it did not meet the end-of-life criteria for short life expectancy.

The cost-effectiveness analysis showed that the incremental cost-effectiveness ratios (ICERs) for AAP improved after adjustments, with the most plausible ICER estimated between £28,600 and £32,800 per quality-adjusted life year (QALY) gained, indicating a more favorable economic evaluation for its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone Acetate for the Treatment of Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer: An Evidence Review Group Perspective of an NICE Single Technology Appraisal. Ramaekers, BLT., Riemsma, R., Tomini, F., 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 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]

Switching from prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer who have progressed on abiraterone acetate plus prednisone may be beneficial, as suggested by the review of four clinical studies.

Potential candidates for this steroid switch include patients with PSA progression but no clinical or radiological progression, those without severe side effects from CYP-17 inhibition, and individuals unfit for chemotherapy or radium-223.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticosteroid switch after progression on abiraterone acetate plus prednisone. Roviello, G., Sobhani, N., Corona, SP., 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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Abiraterone and its place in the treatment of metastatic CRPC. [2021]

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

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

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

Abiraterone Acetate for the Treatment of Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer: An Evidence Review Group Perspective of an NICE Single Technology Appraisal. [2018]

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

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

7. England pubmed.ncbi.nlm.nih.gov

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

8. 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]

9. Japan pubmed.ncbi.nlm.nih.gov

Corticosteroid switch after progression on abiraterone acetate plus prednisone. [2020]

10. 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]