Niraparib Combinations for Prostate Cancer

(QUEST Trial)

Not currently recruiting at 60 trial locations

Overseen By Study Contact

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

Must be taking: GnRHa

Must not be taking: AA, PARPi

Disqualifiers: MDS/AML, Active malignancies, 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: 2

Duration: Up to 37 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of different medication combinations for people with metastatic castration-resistant prostate cancer (mCRPC). It includes drugs like niraparib (a PARP inhibitor), abiraterone acetate, and prednisone to determine the optimal dose and their effects on the cancer. Individuals with mCRPC who may benefit from these drugs could be suitable candidates for this study. Participants will receive treatments tailored to their specific cancer characteristics. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be able to continue gonadotropin releasing hormone analogue (GnRHa) therapy if you are not surgically castrated.

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

Research has shown that niraparib, when combined with abiraterone acetate and prednisone, was generally well-tolerated in past studies. The most common side effects involved blood issues, such as anemia, where the body lacks enough healthy red blood cells. These side effects were mostly manageable. Additionally, using niraparib and abiraterone acetate together has not revealed any new safety concerns compared to using these drugs separately for prostate cancer.

Studies have also tested the combination of niraparib with cetrelimab in patients with advanced prostate cancer that does not respond to hormone therapy. This combination is administered in specific doses and is part of ongoing research to confirm its safety and effectiveness. While there is less information on side effects for this combination, the research aims to determine a safe dose for patients.

Overall, these treatments are under study to ensure they are safe and effective for managing prostate cancer. The ongoing trials aim to confirm these findings further. ^{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 explore innovative combinations that target specific genetic markers. Unlike standard treatments that might not consider genetic variations, the use of niraparib in combination with abiraterone acetate and prednisone specifically targets DNA repair defects, such as BRCA mutations, potentially improving effectiveness for those with these genetic profiles. Additionally, combining niraparib with cetrelimab, an immune checkpoint inhibitor, could enhance the immune system's ability to fight cancer, offering a novel approach different from traditional hormone therapies. These targeted strategies aim to provide more personalized and potentially more effective treatment options for prostate cancer patients.

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

Research has shown that adding niraparib to abiraterone acetate (AA) and prednisone, which participants in this trial may receive, can significantly benefit people with advanced prostate cancer that no longer responds to hormone therapy. One study found that this combination helped patients live longer without their cancer worsening, particularly those with specific genetic markers, such as BRCA mutations. Evidence also indicates that this combination extends overall survival compared to using AA and prednisone alone. Another treatment option in this trial is combining niraparib with cetrelimab, which has shown promise, especially in prostate cancer patients, although more research is needed to fully understand its benefits. Overall, these treatments show promise in slowing the progression of prostate cancer. ^{6 7 8 9 10}

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 who've had disease progression during treatment with abiraterone acetate and PARPi, or stopped these treatments due to side effects. They must have a good performance status (able to carry out daily activities) and resolved any previous treatment toxicities to an acceptable level. Participants should not donate sperm during the trial.

Inclusion Criteria

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

Participant must agree not to donate sperm while on study treatment, and for 3 months following the last dose of study treatment

Side effects from my previous cancer treatments are mild or gone, except for hair loss or some nerve issues.

Exclusion Criteria

I have no active cancers except for certain skin, bladder, or breast cancers, or any cancer considered cured.

I am currently being treated for an infection.

My condition worsened on AA and PARPi treatment, or I stopped due to side effects.

Timeline for a Trial Participant

Pre-screening

Participants are pre-screened for initial eligibility criteria before formal screening

2-4 weeks

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive niraparib in combination with other anti-cancer agents, with dose selection and expansion parts

Up to 37 months

Every 2-4 weeks depending on regimen

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Extension

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone acetate
• Cetrelimab
• Niraparib
• Prednisone 5 mg

Trial Overview

The study is testing combinations of Niraparib with other drugs like Prednisone, Cetrelimab, and Abiraterone acetate in different doses for treating advanced prostate cancer. It aims to find the best dose for phase 2 trials, assess how well tumors respond, check safety, and understand how Niraparib and Abiraterone are absorbed together.

How Is the Trial Designed?

Group I: Combination 3: Niraparib + AA-P Experimental Treatment 3 Interventions

Participants will be assigned to one of three cohorts to receive AA-P with or without niraparib. Participants in the Treatment Phase of this combination will be offered the option to enter the Long-term Extension Phase of the study.

Group II: Combination 2: Dose Expansion: Niraparib + AA-P (Part 2) Experimental Treatment 3 Interventions

Participants will be assigned to one of 4 cohorts based on biomarker status - Cohort 2A (BRCA biallelic loss), 2B (other DRD biallelic loss), 2C (BRCA monoallelic loss), or 2D (other DRD monoallelic loss), and will receive niraparib 200 mg once daily in combination with abiraterone acetate 1000 mg (4\*250 mg) plus 10 mg prednisone (5 mg twice daily) throughout treatment phase. Participants in the Treatment Phase of this combination will be offered the option to enter the Long-term Extension Phase of the study.

Group III: Combination 1:Dose Selection: Niraparib + cetrelimab (Part 1) Experimental Treatment 3 Interventions

Dose regimen 1: The participants will receive niraparib 200 milligram (mg) orally once daily in combination with cetrelimab 240 mg intravenously (IV) once every 2 weeks. Dose regimen 2: The participants will receive niraparib 200 mg orally once daily in combination with cetrelimab 480 mg IV once every 4 weeks in 28-day treatment cycles until disease progression, unacceptable toxicity, death, or the sponsor terminates the study. The safety evaluation team (SET) will determine if an additional cohort is necessary, based on the data from dose regimens 1 and 2. Participants in the Treatment Phase of this combination will be offered the option to enter the Long-term Extension Phase of the study.

Group IV: Combination 1:Dose Expansion: Niraparib + cetrelimab (Part 2) Experimental Treatment 2 Interventions

Participants will be assigned to either Cohort 1A (Biomarker \[BM\] positive \[+\]) or Cohort 1B (BM negative \[-\]) and will receive established RP2D of cetrelimab and niraparib, in Part 2 until disease progression, unacceptable toxicity, death, or the sponsor terminates the study. A futility analysis will be performed for the Cohort 1B after 10 BM- participants are enrolled in Part 2. This cohort will be closed if the response is less than predetermined response rate as outlined in the protocol. Participants in the Treatment Phase of this combination will be offered the option to enter the Long-term Extension Phase of the study.

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?

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

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]

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 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]

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 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]

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]

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]

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 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 Swedish observational study of 119 patients with metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate treatment resulted in similar overall survival rates compared to those seen in the pivotal clinical trial, despite a shorter median treatment duration of 5.6 months versus 7.3 months in the trial.

The findings suggest that while Swedish patients may have characteristics that could limit their treatment benefits, they still achieve comparable survival outcomes, indicating a potentially more cost-effective use of abiraterone in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Value of treatment in clinical trials versus the real world: the case of abiraterone acetate (Zytiga) for postchemotherapy metastatic castration-resistant prostate cancer patients in Sweden. Svensson, J., Andersson, E., Persson, U., et al.[2017]

Citations

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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 ...

2.

urologytimes.com

urologytimes.com/view/published-data-show-benefit-of-niraparib-with-aap-in-hrr-deficient-mcspc

Published data show benefit of niraparib with AAP in HRR- ...

Data showed that adding niraparib to AAP significantly improved radiographic progression-free survival in this patient population.

3.

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

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onclive.com

onclive.com/view/niraparib-plus-abiraterone-and-prednisone-elicits-os-benefit-in-brca1-2-mcrpc

Niraparib Plus Abiraterone and Prednisone Elicits OS ...

Data showed a median OS of 30.4 months among patients who received niraparib plus AAP, compared with 28.6 months among those who received ...

5.

accessdata.fda.gov

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

216793Orig1s000 - accessdata.fda.gov

... data from all. 473 subjects treated with any dose of the niraparib, abiraterone acetate, prednisone combination is sufficient to allow adequate.

6.

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 ...

7.

pubmed.ncbi.nlm.nih.gov

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

Niraparib and Abiraterone Acetate plus Prednisone in ...

The niraparib + AAP safety profile remains unchanged at longer follow-up; adverse events were primarily hematologic and manageable. Conclusions and clinical ...

8.

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 ...

Dr. Gerhardt Attard presented the Phase 3 AMPLITUDE trial: Niraparib and abiraterone acetate plus prednisone for metastatic castration-sensitive ...

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ascopubs.org

ascopubs.org/doi/10.1200/JCO.22.01649

Niraparib and Abiraterone Acetate for Metastatic ...

The safety profile of niraparib + AAP was manageable and consistent with prior studies of each therapy in prostate cancer, with no new safety ...

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jnj.com

jnj.com/media-center/press-releases/johnson-johnson-receives-u-s-fda-priority-review-for-akeega-niraparib-and-abiraterone-acetate-dual-action-tablet-in-brca-mutated-metastatic-castration-sensitive-prostate-cancer

Johnson & Johnson receives U.S. FDA Priority Review for ...

In the AMPLITUDE study, the most common Grade 3/4 adverse events in patients with BRCA-mutated mCSPC were anemia (53.9 percent vs 25.5 percent) ...