Apalutamide + Abiraterone Acetate + Prednisone for Prostate Cancer

Recruiting at 184 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Aragon Pharmaceuticals, Inc.

Must be taking: Androgen deprivation therapy

Must not be taking: Seizure threshold medications

Disqualifiers: Small cell carcinoma, Brain metastases, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 3 years and 4 months

982 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests apalutamide added to a standard treatment for advanced prostate cancer. It targets patients whose cancer has spread and who haven't had chemotherapy. The treatment works by blocking and lowering male hormones that help cancer grow. Apalutamide has shown efficacy in treating different stages of prostate cancer.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, if you are on medications that lower the seizure threshold or products that decrease PSA levels, you must stop them at least 4 weeks before starting. If you were taking a first-generation anti-androgen, a 6-week break is required.

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

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

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

The combination of Abiraterone Acetate and Prednisone has been used in prostate cancer treatment and is generally considered to have an acceptable safety profile, but it can cause side effects like heart issues, liver test abnormalities, fluid retention, and high blood pressure. These side effects are due to the way Abiraterone works in the body. ^{2 6 7 8 9}

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

This drug combination is unique because it combines Apalutamide, which blocks signals that help cancer cells grow, with Abiraterone Acetate and Prednisone, which together reduce hormone levels that fuel prostate cancer. This approach targets the cancer in multiple ways, potentially offering a more comprehensive treatment than using these drugs separately. ^{1 2 6 8 10}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

Men with advanced prostate cancer that hasn't spread to the brain and haven't had chemotherapy. They must have a specific type of tumor (adenocarcinoma), evidence of metastasis, and show cancer progression despite hormone therapy. Prior use of certain anti-androgens is allowed if followed by disease progression.

Inclusion Criteria

My prostate cancer has worsened, shown by rising PSA levels or changes in scans.

I have been diagnosed with prostate adenocarcinoma.

I stopped taking my first-generation anti-androgen medication over 6 weeks ago and my prostate cancer is still getting worse.

Exclusion Criteria

I stopped taking medications that can cause seizures and supplements that lower PSA levels 4 weeks ago.

My prostate cancer is of a specific type: small cell or neuroendocrine.

I have had chemotherapy for prostate cancer only as part of initial treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive apalutamide in combination with abiraterone acetate and prednisone or placebo until disease progression, unacceptable toxicity, or end of treatment

Up to 3 years and 4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years and 10 months

Open-label extension

Participants may opt into continuation of treatment with open-label apalutamide or AAP alone after unblinding

Treatment Details

Interventions

• Abiraterone acetate
• Apalutamide
• Prednisone

Trial Overview The trial tests if adding Apalutamide to standard treatment with Abiraterone Acetate and Prednisone improves outcomes in men with metastatic castration-resistant prostate cancer who haven’t received chemotherapy compared to the standard treatment alone.

Participant Groups

Group I: Group 1: AAP and apalutamide Experimental Treatment 3 Interventions

Participants will receive apalutamide 240 milligram (mg) (4\*60 mg tablets) and abiraterone acetate (AA) 1000 mg (4\*250 mg tablets) once daily on an empty stomach and 5 mg prednisone (P), AAP, twice daily, until disease progression, unacceptable toxicity or end of treatment, whichever occurs first. After unblinding participants will be offered further treatment as defined in the Open-Label Extension (OLE) or Long-Term Extension (LTE) phase (AAP + open label apalutamide or AAP alone).

Group II: Group 2: AAP and Placebo Placebo Group 3 Interventions

Participants will receive matching Placebo of apalutamide and abiraterone acetate (AA) 1000 mg (4\*250 mg tablets) once daily on an empty stomach and 5 mg prednisone (P), AAP, twice daily until disease progression, unacceptable toxicity or end of treatment, whichever occurs first. After unblinding participants will be offered further treatment as defined in the OLE or LTE phase (AAP + open label apalutamide or AAP alone).

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

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer

Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer
• High-risk metastatic hormone-sensitive prostate cancer

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer

Approved in Japan as Zytiga for:

• Metastatic castration-resistant prostate cancer

Who Is Running the Clinical Trial?

Aragon Pharmaceuticals, Inc.

Lead Sponsor

Trials

17

Recruited

5,400+

Findings from Research

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]

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 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 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 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 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]

In a pivotal phase III trial, oral abiraterone acetate combined with prednisone significantly improved overall survival and delayed disease progression in patients with metastatic castration-resistant prostate cancer (CRPC) who had previously undergone docetaxel chemotherapy.

While abiraterone acetate showed a generally acceptable safety profile, it was associated with higher rates of specific adverse events, such as cardiac disorders and fluid retention, compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: in metastatic castration-resistant prostate cancer. Yang, LP.[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, when used with prednisone, improves overall and disease-free survival in patients with both castration-resistant and castration-sensitive prostate cancer.

In a case series of 3 patients, it was found that abiraterone can lead to mineralocorticoid excess and secondary adrenal insufficiency, highlighting the need for awareness and management of these endocrine side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone-Induced Endocrinopathies. Decamps, S., Lis, R., Ekanayake, P.[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]

References

1. 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]

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

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

3. 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]

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

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

5. 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]

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: in metastatic castration-resistant prostate cancer. [2021]

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

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

9. England pubmed.ncbi.nlm.nih.gov

Abiraterone-Induced Endocrinopathies. [2023]

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]