Niraparib + Standard Therapy for Prostate Cancer

(NADIR Trial)

Not currently recruiting at 102 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: NRG Oncology

Must not be taking: Anti-androgens, HAART, PARP inhibitors

Disqualifiers: Metastatic disease, Active malignancy, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding a new drug, niraparib, to standard prostate cancer treatments can prevent the cancer from growing or returning. Niraparib is a targeted therapy that prevents cancer cells from repairing their damaged DNA, potentially leading to their destruction. The study compares different doses of niraparib alongside traditional treatments, including hormone therapy (Gonadotrophin Releasing Hormone) and radiation (Intensity-Modulated Radiation Therapy). Men with prostate cancer at high risk for recurrence and no distant metastases may be eligible. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial requires a washout period of at least 30 days if you have been taking first-generation anti-androgens like bicalutamide, nilutamide, or flutamide. If you are on highly active antiretroviral therapy (HAART) for HIV, you will not be eligible to participate.

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

Research shows that niraparib, a drug tested for prostate cancer, is generally well-tolerated by patients. Studies have found that niraparib can cause some side effects. Common ones include anemia, a low red blood cell count, and neutropenia, a low white blood cell count. However, these side effects are usually manageable.

The FDA has already approved niraparib for certain types of prostate cancer, indicating some confidence in its safety. In previous studies, the safety of niraparib remained consistent, with no unexpected side effects.

This trial is in its early stages, focusing on ensuring the treatment is safe for people. Participants receive close monitoring for any side effects or issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for prostate cancer?

Unlike the standard treatment options for prostate cancer, which typically involve hormone therapy and radiation, the study treatment introduces niraparib, a PARP inhibitor, as an additional component. PARP inhibitors like niraparib target cancer cells by exploiting their DNA repair weaknesses, potentially leading to more effective cancer cell death. Researchers are excited about this because niraparib could enhance the effects of traditional therapies, offering a new angle of attack against prostate cancer that current treatments don't provide. Plus, the study explores different dosing levels of niraparib, which could optimize its effectiveness and minimize side effects, making it a highly promising development in prostate cancer treatment.

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

Studies have shown that niraparib can help treat prostate cancer by blocking a protein called PARP, which cancer cells use to repair damaged DNA. When cancer cells can't repair themselves, they are more likely to die. In this trial, some participants will receive niraparib with standard therapies, such as GnRH agonist androgen suppression therapy and Intensity-Modulated Radiation Therapy (IMRT). Research indicates that combining niraparib with other treatments can lower the chance of cancer returning or spreading. One study found that adding niraparib reduced the risk of disease progression by 37%. This promising evidence suggests niraparib might effectively slow down prostate cancer. ^{2 4 6 7 8}

Who Is on the Research Team?

M. D Michaelson

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for men with high-risk prostate cancer that hasn't spread elsewhere. Eligible participants have a Gleason score of 7 or higher, PSA levels below certain thresholds, and good organ function. They must not have had prior treatments like radical prostatectomy or systemic therapy for prostate cancer and should be willing to use contraception.

Inclusion Criteria

Gleason 8, PSA < 20 ng/mL, and ≥ T2

Hemoglobin ≥ 9.0 g/dL (within 90 days prior to registration)

Serum total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ 1 x ULN (Note: in subjects with Gilberts syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin, and if direct bilirubin is ≤ 1.5 x ULN, subject may be eligible) (within 90 days prior to registration)

Exclusion Criteria

PSA > 150 ng/mL

Definitive clinical or radiologic evidence of metastatic disease

Pathologically positive lymph nodes or nodes > 1.5 cm short axis on CT or MR imaging

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Patients receive niraparib and GnRH agonist therapy. Niraparib continues for 12 months, and GnRH agonist therapy for 24 months. IMRT begins 8 weeks after starting niraparib and GnRH agonist, lasting 6-9 weeks.

24 months

Regular visits for treatment and monitoring

Phase II Treatment

Patients are randomized to receive either standard GnRH agonist therapy or GnRH agonist with niraparib. IMRT begins 8-28 weeks after starting GnRH agonist, lasting 6-9 weeks.

24 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 6 months for 3 years, then annually for 3 years.

6 years

What Are the Treatments Tested in This Trial?

Interventions

• Gonadotrophin Releasing Hormone
• Intensity-Modulated Radiation Therapy
• Niraparib

Trial Overview The study tests the effectiveness of Niraparib (an enzyme blocker) combined with standard radiation and hormonal therapies in preventing the return of high-risk prostate cancer. It's a phase II trial aiming to find the best dose while monitoring side effects.

How Is the Trial Designed?

Group I: Phase II, Arm II (niraparib, GnRH, IMRT) Experimental Treatment 3 Interventions

Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months and concurrent niraparib PO QD (phase I determined dose level) for the first 12 months. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy. Treatment is given in the absence of disease progression or unacceptable toxicity.

Group II: Phase I, Dose Level 3 (niraparib, GnRH, IMRT) Experimental Treatment 3 Interventions

Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months and concurrent niraparib PO QD\* for the first 12 months. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy. Treatment given in the absence of disease progression or unacceptable toxicity. \*Niraparib dose level 3: 200 mg.

Group III: Phase I, Dose Level 2 (niraparib, GnRH, IMRT) Experimental Treatment 3 Interventions

Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months and concurrent niraparib PO QD\* for the first 12 months. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy. Treatment is given in the absence of disease progression or unacceptable toxicity. \*Niraparib dose level 2: 100 mg during IMRT 200 mg otherwise.

Group IV: Phase I, Dose Level 1 (niraparib, GnRH, IMRT) Experimental Treatment 3 Interventions

Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months and concurrent niraparib PO QD\* for the first 12 months. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy. Treatment is given in the absence of disease progression or unacceptable toxicity. \*Niraparib dose level 1: 100 mg.

Group V: Phase II, Arm I (GnRH, IMRT) Active Control 2 Interventions

Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months. Beginning 8-28 weeks after starting GnRH agonist, patients undergo IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy. Treatment is given in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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 study of 318 prostate cancer patients with a median follow-up of 56 months, both radiotherapy combined with GnRHa and radiotherapy combined with bicalutamide showed similar five-year biochemical relapse-free survival rates (85.5% for GnRHa and 88.3% for bicalutamide).

Bicalutamide may be a suitable alternative for patients who prefer to avoid the side effects associated with GnRHa, highlighting the need for further randomized trials to compare these two treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy Plus GnRH Analogue Versus High Dose Bicalutamide: A Case Control Study. Buwenge, M., Deodato, F., Macchia, G., et al.[2020]

Niraparib, a DNA damage repair inhibitor, significantly increased the sensitivity of four head and neck cancer cell lines to both photon and proton radiotherapy, suggesting it could enhance treatment effectiveness.

The study found that niraparib not only reduced colony formation in some cell lines but also increased the relative biological effectiveness (RBE) of protons compared to photons, indicating a potential advantage of proton therapy when combined with niraparib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton and photon radiosensitization effects of niraparib, a PARP-1/-2 inhibitor, on human head and neck cancer cells. Wang, L., Cao, J., Wang, X., et al.[2021]

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. 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- ... At a median follow-up of 30.8 months, data showed that the addition of niraparib led to a 37% reduction in the risk of radiographic progression ...

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

Niraparib in patients with metastatic castration-resistant ... Here, we report the final efficacy and safety results of a multicentre, open-label, phase 2 study of niraparib in patients with mCRPC and tumour DRD whose ...

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

Niraparib and Abiraterone Acetate for Metastatic Castration ... Combination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP.

5. 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)

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

FDA Approval Summary: Niraparib Plus Abiraterone Acetate ... FDA Approval Summary: Niraparib Plus Abiraterone Acetate Fixed Dose Combination for BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer.

7. 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 ( ...

8. 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 ...