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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of two treatments for advanced prostate cancer that may have spread. One group will receive abiraterone and prednisone, which together lower and block male hormones that promote cancer growth. The other group will take darolutamide, a hormone-blocking drug that also inhibits these hormones. The study will compare the side effects of these treatments to determine which might be more effective. Men with confirmed advanced prostate cancer, particularly those already undergoing hormone therapy, are suitable candidates for this trial. As a Phase 2 trial, this 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 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.

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

Earlier studies have shown that combining abiraterone with prednisone is effective and generally safe for patients with advanced prostate cancer. For instance, one study with patients who hadn't received chemotherapy found that this combination improved survival rates. Another study demonstrated that abiraterone with prednisone delayed cancer progression longer than a placebo, with an average delay of 33 months.

Regarding darolutamide, research shows it is well-tolerated. In one study, only a small number of patients needed to lower their dose due to side effects, which were mostly mild or moderate. Darolutamide significantly slowed cancer spread and improved survival chances compared to a placebo.

Both treatments appear safe based on current research. However, individual experiences can differ, so discussing potential risks with a healthcare provider before joining a clinical trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they offer promising new approaches compared to current options like surgery, radiation, and hormone therapy. Abiraterone works by blocking the production of androgens, which are hormones that fuel prostate cancer growth, offering a different angle from traditional therapies. Darolutamide, on the other hand, is a new type of androgen receptor inhibitor that might offer fewer side effects while effectively halting cancer progression. Both treatments could potentially improve outcomes for patients who haven't responded well to existing therapies, providing hope for more effective management of prostate cancer.

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

This trial will compare two treatment options for prostate cancer: one group will receive abiraterone with prednisone, and the other will receive darolutamide. Research has shown that abiraterone with prednisone effectively treats advanced prostate cancer. Specifically, studies found that patients taking this combination had a median time of 33 months before their cancer worsened, compared to 14.8 months for those on a placebo. Additionally, this combination extends survival, even for patients who have previously undergone chemotherapy.

For darolutamide, studies have shown it significantly delays cancer progression compared to a placebo. New data suggests it also lowers PSA levels, which indicate prostate cancer activity, in some patients. When used with androgen deprivation therapy, this treatment has been shown to delay cancer progression and improve patient outcomes. ^{1 2 4 5 6}

Who Is on the Research Team?

Mamta Parikh

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

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 and will follow the study's schedule and rules.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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 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]

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 (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]

Citations

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Real-World Safety and Efficacy Outcomes with Abiraterone ... Abiraterone acetate plus prednisone or prednisolone (AAP) prolongs survival in chemotherapy-naive and docetaxel-experienced patients.

2. 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 ( ...

3. zytigahcp.com zytigahcp.com/efficacy-and-safety/

Metastatic High-Risk CSPC LATITUDE Study A major efficacy outcome was overall survival. The pre-specified interim analysis after 406 deaths showed a statistically significant improvement in OS in ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2059702922000527

Real-world experience of abiraterone acetate plus ... In the interim analysis of the ABItude study, abiraterone showed good clinical effectiveness and safety profile in the chemotherapy-naive setting over a median ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01715285

NCT01715285 | A Study of Abiraterone Acetate Plus Low- ... Impact of abiraterone acetate plus prednisone in patients with castration-sensitive prostate cancer ... outcomes following abiraterone acetate plus prednisone ...

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An Efficacy and Safety Study of Abiraterone Acetate and ... The purpose of this study is to evaluate the efficacy and safety of abiraterone acetate in participants with advanced prostate cancer (a disease in which ...