Niraparib + Abiraterone for Prostate Cancer

Not currently recruiting at 24 trial locations

Overseen By Study Contact

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Must be taking: GnRHa therapy

Must not be taking: Prednisone, Prednisolone

Disqualifiers: Brain metastases, MDS/AML, others

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

Compensation: Varies

Number of Visits: 30

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well different formulations of niraparib and abiraterone acetate work together for individuals with metastatic castration-resistant prostate cancer (a type of prostate cancer that has spread and doesn't respond to lower testosterone levels). Researchers aim to assess how these drug combinations are absorbed in the body and compare their effectiveness. Participants will receive various combinations of the drugs over several phases. This trial suits those with a confirmed diagnosis of this specific prostate cancer, who have not undergone certain past treatments, and who can provide a tumor sample for analysis.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this novel combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you can continue gonadotropin-releasing hormone analogues (GnRHa) therapy if you haven't had a bilateral orchiectomy (surgical removal of both testicles).

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

Research has shown that combining niraparib and abiraterone acetate (AA) with prednisone is generally well-tolerated. Studies have found that the safety profile aligns with expectations for prostate cancer treatment. Most side effects relate to blood health but can be managed. Recent research has not identified any new or unexpected safety issues.

This trial is in its early phase, focusing primarily on assessing the treatment's safety for participants. Although this stage typically involves fewer participants, previous studies suggest that most side effects are manageable, making the treatment a reasonable option for potential participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Niraparib and Abiraterone for prostate cancer because it offers a novel approach compared to the standard treatments like hormone therapy and chemotherapy. Niraparib is a PARP inhibitor, which works by targeting cancer cells' DNA repair mechanism, making them more susceptible to damage and death. This mechanism is different from traditional treatments, which often focus on blocking hormones or killing cells directly. The combination with Abiraterone, which reduces androgen production and slows cancer growth, could potentially enhance treatment effectiveness and offer new hope for patients with advanced prostate cancer. This innovative approach is generating excitement as it could improve outcomes for patients who are not responding to existing therapies.

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

This trial will evaluate different treatment sequences involving niraparib and abiraterone acetate, along with prednisone, for metastatic castration-resistant prostate cancer (mCRPC). Studies have shown that combining these drugs can help treat mCRPC. Research indicates that this combination significantly delays disease progression, as seen in imaging tests. One study found that adding niraparib improved outcomes for patients with certain genetic changes. The data also suggest that niraparib may help patients live longer, although further research is needed to confirm this. These findings support the potential effectiveness of this treatment combination in managing mCRPC. ^{1 2 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 metastatic castration-resistant prostate cancer (mCRPC) who may benefit from the study treatments. Participants should be able to continue hormone therapy if not surgically castrated, have a performance status indicating they are relatively active and can care for themselves, and must provide a tumor sample for genetic testing.

Inclusion Criteria

I can continue hormone therapy during the study if I haven't had surgery to remove my testicles.

I have advanced prostate cancer that is not responding to hormone therapy.

I am fully active or have some restrictions but can still care for myself.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

Treatment

Participants receive various formulations of niraparib and abiraterone acetate to assess bioavailability and bioequivalence

3 weeks

Multiple visits for dosing and monitoring

Extension

Participants continue to receive treatment with niraparib and AAP or AAP alone

Until discontinuation

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

End of treatment visit within 30 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone Acetate (AA)
• Niraparib
• Prednisone

Trial Overview The trial is examining different strengths and formulations of Niraparib and Abiraterone Acetate (AA) under modified fasted conditions to see how well the body absorbs them in men with mCRPC. The study has multiple periods to assess relative bioavailability and bioequivalence.

How Is the Trial Designed?

Group I: Treatment Sequence CDB Experimental Treatment 3 Interventions

Participants will receive Treatment C in Treatment Period 1, followed by Treatment D in Treatment Period 2, followed by Treatment B in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AAP or AAP alone.

Group II: Treatment Sequence CBD Experimental Treatment 3 Interventions

Participants will receive single doses of niraparib and AA using niraparib Formulation 3 as Treatment C in Treatment Period 1, followed by Treatment B in Treatment Period 2, followed by Treatment D in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AAP or AAP alone.

Group III: Treatment Sequence ADB Experimental Treatment 3 Interventions

Participants will receive Treatment A in Treatment Period 1 followed by Treatment D in Treatment Period 2, followed by Treatment B in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AAP or AAP alone.

Group IV: Treatment Sequence ABD Experimental Treatment 3 Interventions

Participants will receive single doses of niraparib and abiraterone acetate (AA) using niraparib Formulation 1 as Treatment A in Treatment Period 1, followed by multiple doses of niraparib and AA using niraparib Formulation 2 as Treatment B in Treatment Period 2, followed by multiple doses of niraparib and AA using niraparib Formulation 4 as Treatment D in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AA-prednisone (AAP) or AAP alone.

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

Niraparib (NIRA) is an effective treatment for patients with metastatic castration-resistant prostate cancer who have specific genetic alterations, showing promising results in a Phase II study.

When combined with abiraterone acetate and prednisone, NIRA demonstrated a manageable safety profile while effectively disrupting cancer cell signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib with Abiraterone Acetate and Prednisone for Metastatic Castration-Resistant Prostate Cancer: Phase II QUEST Study Results. Chi, KN., Fleshner, N., Chiuri, VE., et al.[2023]

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]

The study evaluated the effectiveness of abiraterone acetate combined with prednisone (AA+P) in 53 patients with castration-resistant prostate cancer (mCRPC), showing a good response to this treatment.

Key factors associated with higher survival rates included a longer duration of prostate cancer prior to treatment, lower pain intensity, extended treatment duration with AA+P, and favorable tumor marker levels at 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Metastatic Castration-resistant Prostate Cancer Patients With Abiraterone Acetate and Prednisone and Corresponding Survival Prognostic Factors. Jimenez Romero, ME., Gallego, MC., Navarro Serrato, JC., et al.[2021]

Niraparib at a dose of 200 mg/day was determined to be the recommended phase 2 dose when combined with abiraterone acetate plus prednisone (AAP) for patients with metastatic castration-resistant prostate cancer (mCRPC), as it showed a tolerable safety profile with no new safety signals.

The combination of niraparib with apalutamide resulted in a higher incidence of dose-limiting toxicities, leading to the decision not to further evaluate this combination, highlighting the importance of monitoring drug interactions in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE). Saad, F., Chi, KN., Shore, ND., et al.[2021]

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 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 phase II study involving 41 men with metastatic castration-resistant prostate cancer, increasing the dose of abiraterone acetate from 1000 mg to 2000 mg daily did not result in any significant clinical benefit, as no patients showed a prostate-specific antigen (PSA) decline of 30% or more after 12 weeks.

The study found that factors such as lower baseline circulating androgen levels and individual differences in drug metabolism may contribute to resistance against standard-dose abiraterone therapy, suggesting that simply increasing the dose is not an effective strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Abiraterone Acetate in Men With Castration Resistant Prostate Cancer. Friedlander, TW., Graff, JN., Zejnullahu, K., et al.[2018]

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 study of 95 metastatic castration-resistant prostate cancer (mCRPC) patients, 52% experienced potential drug-drug interactions (DDI) with abiraterone acetate, highlighting the prevalence of polypharmacy in this population.

Patients experiencing pain and those with poorer performance status were found to be at a higher risk for these interactions, suggesting that careful medication reviews by pharmacists are essential to minimize DDI risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential drug-drug interactions with abiraterone in metastatic castration-resistant prostate cancer patients: a prevalence study in France. Bonnet, C., Boudou-Rouquette, P., Azoulay-Rutman, E., et al.[2017]

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]

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. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.17_suppl.LBA5006

Phase 3 AMPLITUDE trial: Niraparib (NIRA) and ... NIRA + AAP significantly improved radiographic progression-free survival (rPFS) in HRR gene–altered metastatic castration-resistant prostate cancer.

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12276826/

FDA Approval Summary: Niraparib Plus Abiraterone Acetate ... The FDA review team concluded that the MAGNITUDE trial demonstrated that the addition of niraparib to AAP provided a statistically significant ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01649

Niraparib and Abiraterone Acetate for Metastatic Castration ... The safety profile of niraparib + AAP was manageable and consistent with prior studies of each therapy in prostate cancer, with no new safety ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/216793Orig1s000MultidisciplineR.pdf

216793Orig1s000 - accessdata.fda.gov characterization of the safety profile of the niraparib, abiraterone acetate, prednisone combination. ... abiraterone and enzalutamide in prostate ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04497844

NCT04497844 | A Study of Niraparib in Combination With ... The purpose of the study is to determine if the combination of niraparib with Abiraterone Acetate (AA) plus prednisone compared with AA plus prednisone