Pre-Surgery Niraparib for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of California, Davis

Must not be taking: PARP inhibitors, Antiandrogens

Disqualifiers: Prior prostate treatment, Severe infection, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of niraparib, a medication administered before surgery, to treat high-risk prostate cancer that hasn't spread beyond the prostate. The goal is to determine if niraparib can stop cancer cell growth by blocking certain enzymes. This trial suits men who have chosen surgery for their prostate cancer and whose tumors have specific DNA repair gene alterations, such as BRCA1/2 or ATM. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take medications that prolong QTc or certain antiretroviral therapies that may interfere with the study drug. It's best to consult with the trial's principal investigator for specific guidance.

Is there any evidence suggesting that niraparib is likely to be safe for humans?

Research has shown that patients have generally tolerated niraparib well in past studies. While effective, it has some noted side effects. Common side effects include anemia, a low red blood cell count, and neutropenia, a low white blood cell count. These side effects are similar to those observed in previous research on prostate cancer treatments with niraparib. However, they were manageable and did not raise new safety concerns. This suggests that despite some risks, the treatment is considered safe for use in clinical settings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about niraparib for prostate cancer because it targets cancer cells differently than standard treatments. Unlike typical therapies that rely on hormone suppression, niraparib is a PARP inhibitor, which means it blocks an enzyme cancer cells use to repair their DNA. This new mechanism can potentially make cancer cells more vulnerable to damage and death, offering a promising option for patients who may not respond to traditional treatments. Additionally, niraparib is taken orally, providing a more convenient option compared to some existing therapies that require in-office administration.

What evidence suggests that niraparib might be an effective treatment for prostate cancer?

Research has shown that niraparib, which participants in this trial will receive, can slow cancer growth. Some studies found it reduced the risk of cancer progression by 37% overall and by 48% in certain patients. Niraparib blocks enzymes that tumor cells need to grow, making it promising for individuals with DNA repair issues. It has proven helpful for patients with advanced prostate cancer, particularly those with specific genetic changes. Although it might not significantly shrink tumors before surgery, it shows potential in managing cancer based on genetic information. ^{1 3 6 7 8}

Who Is on the Research Team?

Marc Dall'Era

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

Men with high-risk localized prostate cancer and specific DNA repair gene alterations (like BRCA1/2, ATM) can join. They must have chosen surgery as primary treatment and not received prior therapies like PARP inhibitors or hormone therapy. Participants need to be able to swallow capsules, avoid sperm donation, use condoms, and have a life expectancy of at least 10 years.

Inclusion Criteria

My prostate cancer is confirmed, localized, and high risk according to NCCN guidelines.

I can swallow whole capsules.

To avoid risk of drug exposure through the ejaculate, male subjects (even if they have undergone a successful vasectomy) must agree while on study therapy (including during dose interruptions) and for 3 months following the last dose of study drug to:

Exclusion Criteria

I have been treated with a PARP inhibitor before.

I have a history of serious irregular heartbeats.

I have a condition that affects how my body absorbs food.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive niraparib orally once daily on days 1-28, repeated every 28 days for up to 3 cycles

12 weeks

3 visits (in-person)

Surgery

Participants undergo standard of care radical prostatectomy following completion of niraparib treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment and surgery

5 years

1 visit at 30 days, every 3 months for 2 years, then every 6 months for up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Niraparib
• Niraparib Tosylate Monohydrate
• Radical Prostatectomy

Trial Overview The trial is testing the effectiveness of Niraparib before surgery in patients with high-risk prostate cancer that hasn't spread elsewhere. The focus is on those with certain gene mutations affecting DNA repair who haven't had previous treatments that could interfere.

How Is the Trial Designed?

Group I: Treatment (niraparib) Experimental Treatment 3 Interventions

Patients receive niraparib PO QD on days 1-28. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Following completion of treatment, patients then undergo standard of care surgery.

Niraparib is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Zejula for:

• Maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy
• Maintenance treatment of adults with platinum-sensitive relapsed high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy

Approved in United States as Zejula for:

• Maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy
• Treatment of adults with advanced ovarian, fallopian tube, or primary peritoneal cancer treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD)-positive status

Approved in Canada as Zejula for:

• Maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

Marc Dall'Era, MD

Lead Sponsor

Trials

2

Recruited

130+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Janssen, LP

Industry Sponsor

Trials

169

Recruited

329,000+

Founded

1953

Headquarters

Beerse, Belgium

Known For

Mental Health Therapies

Top Products

Imodium, Remicade, Invega, Procrit

Joaquin Duato

Janssen, LP

Chief Executive Officer since 2022

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

Dr. Jijo James, MD

Janssen, LP

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 the phase 2 GALAHAD trial involving patients with metastatic castration-resistant prostate cancer and BRCA alterations, niraparib treatment led to significant improvements in health-related quality of life (HRQoL) by cycle 3, which were maintained until cycle 10.

Patients with BRCA alterations experienced more meaningful improvements in overall HRQoL and pain management compared to those with other homologous recombination repair gene alterations, highlighting the potential of niraparib as a targeted therapy for this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life in GALAHAD: A multicenter, open-label, phase 2 study of niraparib for patients with metastatic castration-resistant prostate cancer and DNA-repair gene defects. Smith, MR., Sandhu, S., George, DJ., et al.[2023]

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]

The CALGB 90203 trial aims to compare the effectiveness of radical prostatectomy alone versus neoadjuvant chemotherapy with estramustine and docetaxel in reducing 5-year recurrence rates in high-risk prostate cancer patients, involving around 700 men over a 48-month enrollment period.

The study will also assess the safety and tolerability of the chemotherapy, its impact on tumor characteristics, and overall survival, with a strong statistical power to detect a significant reduction in recurrence rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer and Leukemia Group B (CALGB) 90203: a randomized phase 3 study of radical prostatectomy alone versus estramustine and docetaxel before radical prostatectomy for patients with high-risk localized disease. Eastham, JA., Kelly, WK., Grossfeld, GD., et al.[2019]

In a study of 915 hormone-naïve prostate cancer patients, high-dose parenteral polyoestradiol phosphate (PEP) treatment significantly increased the risk of cardiovascular events, particularly in those with a history of cardiovascular diseases, with 33% experiencing such events during treatment.

PEP was identified as the most important risk factor for cardiac complications, suggesting that while patients without prior cardiovascular issues may have a moderate risk, those with existing conditions should be closely monitored or reconsidered for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Significance of pretreatment cardiovascular morbidity as a risk factor during treatment with parenteral oestrogen or combined androgen deprivation of 915 patients with metastasized prostate cancer: evaluation of cardiovascular events in a randomized trial. Hedlund, PO., Johansson, R., Damber, JE., et al.[2018]

In a study involving 66 patients with androgen-independent prostate carcinoma, the combination of weekly paclitaxel and estramustine phosphate led to a 42% rate of prostate-specific antigen (PSA) decline, indicating significant efficacy in managing the disease.

The treatment was generally well tolerated, with low rates of severe toxicities; however, there was one treatment-related death, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Phase II study of estramustine phosphate plus weekly paclitaxel in patients with androgen-independent prostate carcinoma. Vaughn, DJ., Brown, AW., Harker, WG., et al.[2015]

Niraparib, a recently approved treatment for recurrent platinum-sensitive ovarian cancer, has demonstrated a high oral bioavailability of 72.7% in humans, indicating effective absorption when taken orally.

The study involved six patients who received a therapeutic dose of 300 mg of niraparib, followed by a small intravenous dose to measure its levels in the bloodstream, confirming its potential as a convenient oral treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients. van Andel, L., Rosing, H., Zhang, Z., et al.[2019]

In a study of 50 patients with advanced prostatic carcinoma who had not responded to standard treatments, estramustine phosphate showed a 19% objective response rate and a 36% subjective response rate, with some patients remaining on treatment for up to 3 years without serious side effects.

Combining estramustine phosphate with prednimustine in 21 patients resulted in a 24% objective response rate and 44% subjective improvement, suggesting that this combination therapy may enhance treatment efficacy for advanced prostatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New steroidal alkylating agents in advanced stage D carcinoma of the prostate. Mittelman, A., Catane, R., Murphy, GP.[2013]

Four new water-soluble peptide-paclitaxel conjugates were developed as prodrugs that activate specifically in the presence of prostate-specific antigen (PSA), showing promise for targeted prostate cancer therapy.

The prodrug with an ethylene diamine (EDA) linker demonstrated improved stability and effective conversion to active paclitaxel in PSA-rich environments, indicating its potential for selective cytotoxicity against prostate cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulating paclitaxel bioavailability for targeting prostate cancer. Kumar, SK., Williams, SA., Isaacs, JT., et al.[2015]

The combination of niraparib, a PARP inhibitor, with Radium-223 was found to be safe for treating metastatic castrate-resistant prostate cancer (mCRPC) in men without known BRCA mutations, with manageable dose-limiting toxicities (DLTs) primarily related to blood cell counts.

In a study of 30 patients, the maximum tolerated dose (MTD) varied based on prior chemotherapy exposure, indicating that personalized dosing may be necessary; further research is needed to explore biomarkers that could predict treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Niraparib in Combination with Radium-223 for the Treatment of Metastatic Castrate-Resistant Prostate Cancer. Quinn, Z., Leiby, B., Sonpavde, G., et al.[2023]

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. news-medical.net news-medical.net/news/20251007/New-drug-combination-could-delay-the-progression-of-advanced-prostate-cancer.aspx

New drug combination could delay the progression of ... Overall, niraparib reduced the risk of cancer growth by 37% compared to AAP alone in all patients and by 48% in the subgroup of patients with ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9361481/

Niraparib in patients with metastatic castration-resistant ... Niraparib is tolerable and has anti-tumour activity in heavily pre-treated patients with mCRPC and DRD, particularly in those with BRCA alterations. Funding.

4. health.ucdavis.edu health.ucdavis.edu/alzheimers-research/news/headlines/biomarkers-hold-clue-in-treating-aggressive-prostate-cancer/2025/05

Biomarkers hold clue in treating aggressive prostate cancer While the drug didn't dramatically shrink tumors before surgery, the study showed the potential of using genetic testing and blood-based ...

5. 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

6. journals.lww.com journals.lww.com/atmr/fulltext/2024/07000/safety_and_efficacy_of_niraparib_in_metastatic.8.aspx

Safety and Efficacy of Niraparib in Metastatic Castration-re... Niraparib has been found to have a positive impact on rPFS, TSP and TCC, but it has also been associated with some adverse events, such as anaemia, neutropenia ...

7. 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 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02854436

NCT02854436 | An Efficacy and Safety Study of Niraparib ... The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of niraparib in men with metastatic castration-resistant prostate cancer ( ...