Apalutamide + Abiraterone Acetate + Prednisone for Prostate Cancer

Not currently recruiting at 226 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a new combination of medications for prostate cancer that has spread and does not respond to standard hormone therapy. The study compares two groups: one receives apalutamide (a hormone therapy), abiraterone acetate, and prednisone, while the other receives abiraterone acetate and prednisone with a placebo (a pill with no active ingredient). The trial seeks men with prostate cancer that has spread, continued to grow despite hormone therapy, and who have not yet received chemotherapy. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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.

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

Research shows that combining apalutamide, abiraterone acetate, and prednisone is generally safe and well-tolerated for treating advanced prostate cancer that no longer responds to hormone therapy. In earlier studies, patients trying this combination for the first time had promising results, with about 80% continuing their treatment without major issues.

Some patients experienced side effects, but these were manageable, meaning they weren't too severe or could be controlled. Previous studies have supported the safety of using these medications together and showed improvements in cancer treatment.

Overall, evidence suggests that this treatment combination is quite safe for those considering joining a clinical trial. It's important to remember that every patient is different, so discussing potential side effects with a healthcare provider is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about combining apalutamide with abiraterone acetate and prednisone for prostate cancer because this approach targets the disease in a multi-faceted way. Apalutamide is an androgen receptor inhibitor that works by blocking the signals that prostate cancer cells need to grow, adding a layer of action beyond what abiraterone acetate and prednisone provide alone. Unlike standard treatments that might focus on a single pathway, this combination aims to hit multiple targets, potentially slowing disease progression more effectively. This unique combination could offer a more comprehensive attack on cancer cells, making it a promising option for patients.

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

Research has shown that adding apalutamide to treatment with abiraterone acetate and prednisone can significantly improve outcomes for people with metastatic castration-resistant prostate cancer (mCRPC). In this trial, one group will receive this combination, which studies have found leads to a higher rate of confirmed responses in prostate-specific antigen levels, indicating treatment effectiveness. Apalutamide also reduces the risk of death by 26% compared to using only abiraterone acetate. Additionally, using this combination after surgery has been linked to better cancer control. Overall, these findings suggest that this treatment can be more effective than standard options for people with this type of prostate cancer. ^{2 4 6 7 8}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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 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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9377412/

Apalutamide plus abiraterone acetate and prednisone in ... The addition of apalutamide to abiraterone-prednisone versus abiraterone-prednisone alone resulted in a significantly higher rate of confirmed ≥ ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12224120/

Overall survival in patients with metastatic castration ... Apalutamide was associated with a 26% reduction in the risk of mortality compared with abiraterone acetate by 24 months post-treatment initiation.

3. nature.com nature.com/articles/s41391-024-00929-6

Survival outcomes of apalutamide as a starting treatment First-line APA + ADT in mHSPC was associated with statistically significantly longer OS, longer TTCR, and faster and deeper PSA responses than other life- ...

4. targetedonc.com targetedonc.com/view/abiraterone-prednisone-apalutamide-improves-prostate-cancer-outcomes-leaves-hrqol-unaffected

Abiraterone, Prednisone, Apalutamide Improves Prostate ... Oncological outcomes improved with the addition of abiraterone acetate (Zytiga) plus prednisone (AAP) and apalutamide (Erleada) after radical prostatectomy.

5. yoda.yale.edu yoda.yale.edu/clinical-trial/nct02257736-a-phase-3-randomized-placebo-controlled-double-blind-study-of-jnj-56021927-in-combination-with-abiraterone-acetate-and-prednisone-versus-abiraterone-acetate-and-prednisone-in-subjects-w/

NCT02257736 - The YODA Project 2023-5236 : Understanding the Symptom Experience of Abiraterone and the Effect on Quality of Life for Men with metastatic Prostate Cancer. 2023-5198 : ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5543693/

Safety and Antitumor Activity of Apalutamide (ARN-509) in ... Apalutamide was safe, well tolerated, and demonstrated clinical activity in mCRPC with 80% of AAP-naïve and 43% of post-AAP patients remaining on treatment for ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02257736

Study Details | NCT02257736 | An Efficacy and Safety ... The purpose of this study is to compare the radiographic progression-free survival (rPFS) of apalutamide in combination with abiraterone acetate (AA) plus ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.5015

A prospective trial of apalutamide and abiraterone acetate ... We designed the PANTHER trial to estimate clinical outcomes among Black and White pts with mCRPC treated with apalutamide, abiraterone, plus prednisone.