Niraparib + Abiraterone Acetate and Prednisone for Prostate Cancer

(AMPLITUDE Trial)

Not currently recruiting at 618 trial locations

Overseen By Study Contact

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must be taking: Androgen deprivation therapy

Must not be taking: PARP inhibitors, Long-term corticosteroids

Disqualifiers: Adrenal dysfunction, MDS/AML, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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 47 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding niraparib, a PARP inhibitor, to a treatment of abiraterone acetate plus prednisone is more effective at slowing prostate cancer progression than using abiraterone acetate and prednisone alone. It targets men with a specific type of prostate cancer that has metastasized and involves a gene mutation affecting DNA repair. Men with this type of prostate cancer who have already begun hormone therapy (androgen deprivation therapy) and meet other specific criteria may be suitable for this trial. 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.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop your current medications. However, you must continue androgen deprivation therapy (ADT) and cannot use long-term systemic corticosteroids during the study.

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

In earlier studies, patients generally tolerated the combination of niraparib with abiraterone acetate and prednisone well. Research shows that while some side effects occurred, they were mostly manageable. The most common side effects included tiredness, nausea, and anemia, which is a low red blood cell count.

Notably, the FDA has already approved niraparib for other uses, indicating a well-understood safety profile. This approval gives doctors confidence in its safety based on past experiences. However, potential participants should discuss any concerns with their healthcare provider to understand how these findings might relate to their own health. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Niraparib with Abiraterone Acetate and Prednisone for prostate cancer because it introduces a new mechanism of action. While standard treatments like Abiraterone Acetate and Prednisone primarily target hormone pathways to slow cancer growth, Niraparib is a PARP inhibitor. This means it works by targeting cancer cells' DNA repair process, potentially making the treatment more effective at killing cancer cells. This dual approach could improve outcomes by attacking the cancer from multiple angles, which is why there’s a lot of anticipation around this treatment combination.

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

Research has shown that combining niraparib with abiraterone acetate and prednisone may help treat metastatic castration-sensitive prostate cancer in patients with certain gene mutations. In this trial, participants in one arm will receive this combination. A major study demonstrated that this approach significantly extended the time patients lived without their cancer worsening, compared to the usual treatment. Patients also experienced a longer period before their symptoms worsened. Additionally, a trend suggests that patients might live longer overall with the niraparib combination. These findings indicate that this treatment could be more effective for those with specific genetic changes in their cancer. ^{1 2 4 5 6}

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 prostate cancer that has spread and is sensitive to hormone therapy can join if they have specific gene changes related to DNA repair. They must have started hormone treatment at least two weeks before joining, but not had extensive prior treatments like radiation or certain drugs.

Inclusion Criteria

I started hormone therapy for my cancer more than 14 days ago and am willing to continue it.

I have prostate cancer and have had limited prior treatments for it.

My cancer has spread, confirmed by scans.

Exclusion Criteria

I am not on long-term steroids higher than 5mg of prednisone or equivalent.

I have been treated with a PARP inhibitor before.

I have or had myelodysplastic syndrome or acute myeloid leukemia.

Timeline for a Trial Participant

Prescreening

Biomarker evaluation for eligibility only

2-4 weeks

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive niraparib with abiraterone acetate plus prednisone or placebo with abiraterone acetate plus prednisone in 28-day cycles

Up to 47 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 78 months

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone acetate (AA)
• Niraparib
• Prednisone

Trial Overview The trial tests if adding Niraparib (a drug for DNA repair defects) to Abiraterone Acetate and Prednisone improves outcomes in men whose prostate cancer has spread. Participants are randomly assigned to either the combination treatment or just AA plus prednisone.

How Is the Trial Designed?

Group I: Niraparib with Abiraterone Acetate plus Prednisone (AAP) Experimental Treatment 3 Interventions

Participants will receive the following in each 28-day treatment cycle: niraparib 200 milligrams (mg), abiraterone acetate (AA) 1000 mg plus prednisone 5 mg once daily.

Group II: AA plus Prednisone (AAP) Active Control 3 Interventions

Participants will receive the following in each 28-day treatment cycle: matching placebo for Niraparib along with AA 1000 mg plus prednisone 5 mg once daily.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

In a study of 133 patients with non-metastatic castration-resistant prostate cancer, abiraterone acetate (AA) plus prednisone showed comparable overall survival and cancer-specific survival to enzalutamide (Enz) over a median follow-up of 36 months.

However, patients treated with AA plus prednisone had a significantly higher risk of non-cancer-caused death compared to those treated with Enz, suggesting that while both treatments are effective, AA plus prednisone may pose additional safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world survival outcome comparing abiraterone acetate plus prednisone and enzalutamide for nonmetastatic castration-resistant prostate cancer. Tsujino, T., Tokushige, S., Komura, K., et al.[2023]

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 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]

In a study of 148 patients with metastatic castration-resistant prostate cancer, maintaining abiraterone acetate plus prednisone (AAP) during docetaxel treatment did not improve radiographic progression-free survival compared to docetaxel plus prednisone alone, with rates of 34.9% and 33.9% respectively after 12 months.

The combination of docetaxel and AAP resulted in significantly higher rates of severe neutropenia (59.6%) compared to docetaxel plus prednisone (27.7%), suggesting that continuing AAP may increase treatment-related risks without providing additional benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II randomised trial of abiraterone acetate plus prednisone in combination with docetaxel or docetaxel plus prednisone after disease progression to abiraterone acetate plus prednisone in patients with metastatic castration-resistant prostate cancer: The ABIDO-SOGUG trial. Climent, MA., Font, A., Durán, I., et al.[2022]

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 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]

Abiraterone acetate (AA) combined with prednisone shows favorable safety and efficacy outcomes in treating metastatic prostate cancer, particularly in patients who are asymptomatic or have mild symptoms.

The treatment is generally well tolerated, but it is important to be aware of its known toxicity profile, including mineralocorticoid and corticosteroid-related adverse events, as well as hepatotoxicity, which can inform clinical decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A drug safety evaluation of abiraterone acetate in the treatment of prostate cancer. Castellan, P., Castellucci, R., Marchioni, M., et al.[2019]

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]

Citations

1. nature.com nature.com/articles/s41591-025-03961-8

Niraparib and abiraterone acetate plus prednisone for ... The data for overall survival, a key secondary endpoint, are immature (193/389 events) but favor niraparib (hazard ratio = 0.79 (95% confidence ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40328571/

Niraparib and Abiraterone Acetate plus Prednisone in ... The phase 3 MAGNITUDE trial previously met its primary endpoint of an improvement in radiographic progression-free survival with niraparib + abiraterone ...

3. esmo.org esmo.org/oncology-news/combining-niraparib-with-abiraterone-acetate-and-prednisone-significantly-improves-rpfs-in-patients-with-mcspc-harbouring-brca1-2-or-other-hrr-gene-alterations

Combining Niraparib with Abiraterone Acetate and ... Clinical benefit was further supported by statistically significant and clinically meaningful improvements in time to symptomatic progression.

4. urotoday.com urotoday.com/conference-highlights/asco-2025/asco-2025-prostate-cancer/161080-asco-2025-phase-3-amplitude-trial-niraparib-and-abiraterone-acetate-plus-prednisone-for-metastatic-castration-sensitive-prostate-cancer-patients-with-alterations-in-homologous-recombination-repair-genes.html

ASCO 2025: Phase 3 AMPLITUDE Trial: Niraparib and ... The AMPLITUDE trial is a randomized, double-blind, placebo-controlled phase 3 study evaluating the efficacy of a fixed daily tablet of niraparib (200 mg)

5. sciencedirect.com sciencedirect.com/science/article/pii/S2588931125001075

Niraparib and Abiraterone Acetate plus Prednisone in ... The MAGNITUDE final analysis showed a trend towards better overall survival with niraparib + abiraterone acetate and prednisone (AAP) versus placebo + AAP.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03748641

NCT03748641 | A Study of Niraparib in Combination With ... The purpose of this study is to evaluate the effectiveness of niraparib in combination with abiraterone acetate plus prednisone (AAP) compared to AAP and ...