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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well niraparib, when given before surgery, works in treating patients with high risk prostate cancer that has not spread to other parts of the body (localized) and alterations in deoxyribonucleic acid (DNA) repair pathways. Niraparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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.

What data supports the idea that Pre-Surgery Niraparib for Prostate Cancer is an effective drug?

The available research shows that Niraparib, when used in combination with other treatments like abiraterone acetate and prednisone, has shown promising results for patients with metastatic castration-resistant prostate cancer. Specifically, the phase II QUEST study indicated that this combination was effective and had a manageable safety profile. Additionally, the GALAHAD trial demonstrated that patients with certain genetic alterations experienced improvements in their quality of life and pain levels when treated with Niraparib. These findings suggest that Niraparib can be an effective option for treating prostate cancer, especially in patients with specific genetic backgrounds. ^{1 2 3 4 5}

What safety data is available for pre-surgery Niraparib treatment in prostate cancer?

The provided research does not contain specific safety data for pre-surgery Niraparib treatment in prostate cancer. The studies focus on other treatments such as parenteral oestrogen, estramustine phosphate, paclitaxel, and docetaxel, but do not mention Niraparib or its safety profile in the context of prostate cancer treatment. ^{6 7 8 9 10}

Is the drug Niraparib a promising treatment for prostate cancer?

Yes, Niraparib shows promise as a treatment for prostate cancer. It has been effective in improving the quality of life and managing symptoms in patients with specific genetic profiles, particularly those with BRCA gene alterations. Studies have shown that it can be combined with other therapies to enhance its effectiveness, making it a hopeful option for treating advanced prostate cancer. ^{1 2 3 4 5}

Research Team

Marc Dall'Era

Principal Investigator

University of California, Davis

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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 Business School

Biljana Naumovic

Janssen, LP

Chief Medical Officer since 2023

MD from Belgrade University Medical School

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

References

1. Germany 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. [2019]

2. Germany 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). [2021]

3. England pubmed.ncbi.nlm.nih.gov

Niraparib with Abiraterone Acetate and Prednisone for Metastatic Castration-Resistant Prostate Cancer: Phase II QUEST Study Results. [2023]

4. United States 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. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Phase I Study of Niraparib in Combination with Radium-223 for the Treatment of Metastatic Castrate-Resistant Prostate Cancer. [2023]

6. England 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. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

New steroidal alkylating agents in advanced stage D carcinoma of the prostate. [2013]

8. England pubmed.ncbi.nlm.nih.gov

Modulating paclitaxel bioavailability for targeting prostate cancer. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Multicenter Phase II study of estramustine phosphate plus weekly paclitaxel in patients with androgen-independent prostate carcinoma. [2015]

10. United States 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. [2019]