PARP Inhibitors for Ovarian Cancer

(4PDQ Trial)

Age: Any Age

Sex: Female

Trial Phase: Academic

Sponsor: University of Saskatchewan

Must be taking: PARP inhibitors

Disqualifiers: Ineligible for PARPi, Refusal HRD testing

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-12 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of niraparib, a PARP inhibitor, for patients with ovarian cancer who have difficulty repairing their DNA. It focuses on those who respond to platinum-based chemotherapy and have either homologous recombination deficiency (HRD) or do not (HRP). Researchers aim to determine if the benefits of niraparib outweigh the side effects, particularly for those without the genetic weakness. Eligible participants are women with advanced ovarian cancer who can communicate in English for study requirements.

As an unphased trial, this study provides a unique opportunity for patients to contribute to groundbreaking research that could shape future treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that niraparib is safe for ovarian cancer patients?

Research shows that niraparib is generally well-tolerated as a maintenance treatment for ovarian cancer, with a mostly manageable safety profile. However, some patients experience side effects, including common issues like low blood cell counts.

In one study, almost all patients taking niraparib experienced treatment-related side effects. Despite this, long-term evidence suggests that the benefits of using niraparib for ovarian cancer often outweigh the risks. Discuss any concerns with a doctor, who can help explain how these findings might apply to individual cases. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Niraparib is unique because it is a PARP inhibitor specifically designed to target ovarian cancer cells with DNA repair deficiencies. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, Niraparib zeroes in on cancer cells with specific genetic weaknesses, potentially leading to fewer side effects. Researchers are excited about Niraparib because it offers a more tailored treatment approach, which could improve outcomes for patients with ovarian cancer, especially those with homologous recombination deficiency (HRD).

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

Research has shown that niraparib, a PARP inhibitor, can slow the progression of ovarian cancer, particularly in patients with homologous recombination deficiency (HRD). Studies have found that niraparib extends the time before the cancer worsens. Specifically, 35% of patients with HRD remained well after five years, compared to 16% of those not taking niraparib. However, niraparib may cause more severe side effects than other treatments, potentially affecting quality of life, especially in the initial weeks of treatment. Overall, niraparib offers significant benefits for certain patients, particularly those with DNA repair issues, such as BRCA mutations. Participants in this trial will undergo testing for HRD status to determine their treatment approach. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for ovarian cancer patients in Saskatchewan who've responded to platinum-based chemotherapy and will undergo HRD testing. It's designed to help those with defective DNA repair mechanisms decide if PARPi therapy, specifically niraparib, is beneficial considering its impact on quality of life.

Inclusion Criteria

Able to provide oral consent and complete questionnaires in English as per study protocol

I have advanced ovarian cancer.

Exclusion Criteria

I refuse to have HRD testing.

I cannot receive maintenance PARPi therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

HRD Testing

HRD testing is performed for ovarian cancer patients to determine eligibility for PARPi therapy

2 weeks

Treatment

Participants receive PARPi therapy, with a focus on evaluating treatment outcomes and quality of life

6-12 weeks

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Niraparib

Trial Overview The study tests the effectiveness of a decision aid for using PARP inhibitors (PARPi) like niraparib or olaparib in ovarian cancer patients with homologous recombination deficiency (HRD). It aims to balance treatment benefits against side effects and decreased quality of life during initial weeks.

How Is the Trial Designed?

Group I: HRD Tested Experimental Treatment 1 Intervention

HRP patients are given a decision aid, while HRD patients are not given a decision.

Who Is Running the Clinical Trial?

University of Saskatchewan

Lead Sponsor

Trials

261

Recruited

156,000+

Published Research Related to This Trial

In a real-world study of 22 ovarian cancer patients treated with niraparib at a dose of 200 mg/day, the objective response rate was 33.3%, indicating promising efficacy, especially in patients with homologous recombination deficiency (HRD).

The most common adverse events included nausea, thrombocytopenia, and anemia, with severe thrombocytopenia managed through dose adjustments, suggesting that niraparib can be tolerated with appropriate monitoring and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of niraparib for ovarian cancer: a single-center observational study from China. Ni, J., Cheng, X., Zhao, Q., et al.[2021]

Niraparib, a PARP inhibitor, has been shown to be safe for long-term use in patients with recurrent ovarian cancer, with a significant reduction in treatment-emergent adverse events (TEAEs) over time, particularly in the first month of treatment.

The study highlighted the importance of dose adjustments, as the incidence of severe side effects like thrombocytopenia decreased significantly after the initial month, indicating that careful management can enhance the safety of niraparib therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo: Results from the phase III ENGOT-OV16/NOVA trial. Mirza, MR., Benigno, B., Dørum, A., et al.[2021]

Niraparib, a PARP inhibitor used for ovarian cancer maintenance therapy, is associated with grade 3/4 thrombocytopenia, particularly in patients with renal insufficiency (CrCl <60 mL/min) and low albumin levels (<3.5 g/dL).

In vitro studies confirmed a direct concentration-dependent relationship between niraparib and platelet toxicity, indicating that higher drug concentrations can lead to more significant decreases in platelet counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identifying the need to refine the potential patient risk factors for niraparib-induced thrombocytopenia. Smith, JA., Le, T., Martin, GA., et al.[2019]

Niraparib is the first PARP inhibitor approved for ovarian cancer treatment in patients without BRCA mutations, showing good tolerability and manageable hematologic side effects, especially with new dose modification guidelines.

Current research is exploring niraparib's effectiveness as a maintenance therapy after platinum-based chemotherapy and in recurrent high-grade serous ovarian cancer, highlighting the need for better biomarkers to identify which patients will benefit most from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib for the treatment of ovarian cancer. Essel, KG., Moore, KN.[2019]

Niraparib is an FDA and EMA-approved oral PARP inhibitor for maintenance treatment in women with recurrent ovarian cancer who have responded to platinum-based chemotherapy, showing efficacy in both BRCA mutated and wild-type cancers.

While niraparib is effective, it can cause significant hematologic toxicities, such as thrombocytopenia and anemia, necessitating dose adjustments for certain patients to minimize these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The poly (ADP ribose) polymerase inhibitor niraparib: Management of toxicities. Moore, KN., Mirza, MR., Matulonis, UA.[2019]

Niraparib, a PARP inhibitor, significantly improves progression-free survival in patients with advanced epithelial ovarian cancer, but nearly all patients (≥99%) experience treatment-emergent adverse events, with 51-74% experiencing severe (grade ≥3) events.

An individualized starting dose of niraparib based on body weight and platelet count leads to fewer severe adverse events and dose modifications, suggesting a tailored approach can enhance safety while maintaining treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and management of niraparib monotherapy in ovarian cancer clinical trials. Monk, BJ., González-Martin, A., Buckley, L., et al.[2023]

In a phase 3 trial involving 553 patients with platinum-sensitive, recurrent ovarian cancer, niraparib significantly improved progression-free survival compared to placebo, with median durations of 21.0 months versus 5.5 months for patients with gBRCA mutations, and 12.9 months versus 3.8 months for those with homologous recombination deficiency.

While niraparib was effective, it was associated with moderate bone marrow toxicity, with common grade 3 or 4 adverse events including thrombocytopenia (33.8%), anemia (25.3%), and neutropenia (19.6%), which were managed through dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. Mirza, MR., Monk, BJ., Herrstedt, J., et al.[2022]

Niraparib, a treatment for recurrent ovarian cancer, has a high dose reduction rate of 68.9% due to treatment-emergent adverse events, with thrombocytopenia being a notable cause for 3.3% of patients.

Baseline body weight and platelet count are significant predictors for the risk of severe thrombocytopenia, suggesting that patients with a body weight under 77 kg or platelet count below 150,000/µl may benefit from starting at a lower dose of 200 mg/day without compromising progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and dose modification for patients receiving niraparib. Berek, JS., Matulonis, UA., Peen, U., et al.[2021]

Niraparib is the first FDA- and EMA-approved PARP inhibitor for maintenance therapy in platinum-sensitive ovarian cancer, effective regardless of BRCA status in first-line treatment.

The review highlights niraparib's pharmacological properties and summarizes efficacy and safety data from key trials, indicating its significant role in improving treatment outcomes for ovarian cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib and Advanced Ovarian Cancer: A Beacon in the Non-BRCA Mutated Setting. Maiorano, MFP., Maiorano, BA., Biancofiore, A., et al.[2023]

Niraparib, a PARP inhibitor for recurrent ovarian cancer, showed no significant changes in its pharmacokinetics when taken with a high-fat meal compared to fasting, indicating it can be safely taken with or without food.

The study demonstrated that niraparib was well-tolerated and had similar adverse events regardless of the meal condition, confirming its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of food on the pharmacokinetics of niraparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, in patients with recurrent ovarian cancer. Moore, K., Zhang, ZY., Agarwal, S., et al.[2019]

In a phase 3 trial involving 733 patients with newly diagnosed advanced ovarian cancer, niraparib significantly improved progression-free survival compared to placebo, with a median of 21.9 months versus 10.4 months for patients with homologous-recombination deficiency.

Niraparib also demonstrated a notable overall survival rate of 84% at 24 months, with manageable side effects, including anemia and thrombocytopenia, but no treatment-related deaths, indicating its safety and efficacy as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. González-Martín, A., Pothuri, B., Vergote, I., et al.[2019]

Niraparib significantly prolongs progression-free survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer, with a median PFS of 18.3 months compared to 5.4 months for placebo, indicating a 68% reduction in the risk of disease progression or death.

The treatment was generally safe, though 50.8% of patients experienced grade ≥3 adverse events, with the most common being decreased neutrophil count and anemia, highlighting the importance of monitoring for side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial&#9734;. Wu, XH., Zhu, JQ., Yin, RT., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10663182/

Efficacy and Safety of Niraparib as First-Line Maintenance ... The results of HRD testing revealed that 66 (33.2%) patients were positive, 52 (26.1%) negative, and 81 (40.7%) not known. It is noteworthy that ...

2. zejulahcp.com zejulahcp.com/efficacy/

PRIMA Clinical Study | Efficacy | ZEJULA (niraparib) for HCPs Find study data for PRIMA, a clinical trial examining the efficacy of ZEJULA (niraparib) as first-line maintenance in HRD-positive patients with ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534%2824%2903762-1/fulltext

final overall survival results from the PRIMA/ENGOT-OV26/ ... The 5-year PFS rate was 22% in the niraparib arm versus 12% in the placebo arm in the overall population and 35% versus 16% in the HRd ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.5587

Efficacy of niraparib in patients with advanced ovarian cancer Niraparib improves PFS and lowers the time to first subsequent therapy in patients with advanced ovarian cancer.

5. facingourrisk.org facingourrisk.org/XRAY/PARP-inhibitor-ovarian-cancer-survival

Niraparib improves outcomes in patients with newly ... This study looked at the effectiveness and safety of niraparib (Zejula), a PARP inhibitor, as maintenance therapy in newly diagnosed ovarian cancer patients.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35049703/

Safety Profile of Niraparib as Maintenance Therapy for ... Niraparib is considered an effective and well-tolerated choice, with an improved safety profile, for the maintenance treatment of EOC ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0301211525000466

Safety of niraparib-based regimens in patients with ovarian ... Our meta-analysis suggests that niraparib is associated with a tolerable safety profile in ovarian cancer maintenance treatment, with hematological toxicities ...

8. nature.com nature.com/articles/s41598-024-63600-z

Safety assessments and clinical features of PARP ... This retrospective study included 181 patients with ovarian cancer who received olaparib or niraparib at two independent hospitals in Japan between May 2018 ...

9. journals.lww.com journals.lww.com/annals-of-medicine-and-surgery/fulltext/2025/04000/assessment_of_safety_of_niraparib_maintenance.64.aspx

Assessment of safety of niraparib maintenance therapy in... The PRIMA 2 trial 15 reported treatment-emergent adverse events (TEAEs) in 99% of niraparib-treated patients and 93.9% of control-treated ...