Alternative Dosing of Niraparib for Ovarian Cancer

Overseen By Dr. Allan Covens, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Sunnybrook Health Sciences Centre

Must be taking: Platinum-based chemotherapy

Must not be taking: PARP inhibitors

Disqualifiers: Pregnancy, Myelodysplastic syndrome, HIV, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 cycles

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different methods of administering niraparib, a medication, to assess its effects on women with newly diagnosed advanced ovarian cancer. Researchers aim to determine the frequency of side effects, the need for dose adjustments, and the duration of cancer control after two years. Women with advanced ovarian cancer who have responded well to specific chemotherapy treatments may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude patients receiving certain prohibited medications. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research has shown that niraparib, a treatment for ovarian cancer, has a well-understood safety record, particularly in preventing cancer recurrence in some patients. Studies have found it to be generally well-tolerated, especially when doses are adjusted early based on side effects.

Common side effects include nausea, affecting 65% of patients in studies, and low blood counts. Adjusting the dose often manages these side effects. The treatment has helped over 1,000 women live longer without their disease worsening.

Overall, while niraparib can cause some side effects, particularly related to blood, early and proper dose adjustments play a crucial role in managing these effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Niraparib is unique because it offers a personalized dosing approach for ovarian cancer treatment, unlike the standard fixed-dose regimens. While typical treatments like chemotherapy broadly target fast-growing cells, Niraparib is a PARP inhibitor that specifically targets cancer cells' DNA repair pathways, potentially leading to fewer side effects and improved effectiveness. Researchers are excited about its potential to tailor the dosage to individual patient needs, which could enhance the balance between efficacy and tolerability.

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

Research has shown that niraparib can help patients with advanced ovarian cancer live longer without their cancer worsening. Studies found that patients who took niraparib experienced more time before cancer progression compared to those who did not take it. Women with a specific genetic marker called HRD-positive ovarian cancer experienced significant benefits from this treatment. Overall, niraparib consistently slows the progression of ovarian cancer, making it a promising option for patients with this condition. ^{6 7 8 9 10}

Who Is on the Research Team?

Dr. Allan Covens, MD

Principal Investigator

Sunnybrook Research Institute

Are You a Good Fit for This Trial?

This trial is for women over 18 with newly diagnosed high-grade ovarian cancer who've completed certain chemotherapies. They must be post-menopausal, surgically sterilized, or use contraception. Exclusions include pregnancy, previous severe reactions to niraparib or PARP inhibitors, and certain health conditions.

Inclusion Criteria

Patients must be able to understand the study, agree to participate and provide written, informed consent

My organs are functioning well enough for me to join the trial.

I am a woman and at least 18 years old.

Exclusion Criteria

I have not received a live vaccine in the last 30 days.

I have a serious heart condition.

You have taken another experimental treatment within the past 4 weeks or 5 times the length of time it takes for the treatment to leave your body, whichever is longer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral niraparib in a dose escalation design starting at 100 mg PO daily for the first two cycles, then 200 mg PO daily for the third and fourth cycle.

4 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival at 24 months.

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Niraparib

Trial Overview

The trial tests alternative dosing of Niraparib in patients with advanced stage ovarian cancer to see how it affects the rate of side effects, treatment interruptions, dose reductions/discontinuations and progression-free survival at 24 months.

How Is the Trial Designed?

Group I: Single arm- Niraparib Experimental Treatment 1 Intervention

Oral niraparib will be administered in a dose escalation design where patients will start at a dose of 100 mg PO daily for the first two cycles, then 200 mg PO daily for the third and fourth cycle. Patients will remain on the individualized dose until either they experience an adverse event and require a dose reduction or they have disease progression.

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?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

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, 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]

In a Phase 2 study involving 20 Japanese women with heavily pretreated ovarian cancer, niraparib demonstrated an objective response rate of 35%, indicating that it can effectively reduce tumor size in some patients.

The treatment was generally well-tolerated, with a high disease control rate of 90%, although common side effects included anemia and nausea, and 70% of patients experienced dose reductions or interruptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer. Okamoto, A., Kondo, E., Nakamura, T., et al.[2021]

Niraparib significantly extends progression-free survival in patients with newly diagnosed advanced ovarian cancer, showing efficacy in both homologous-recombination deficiency positive (HRd) and negative (HRp) populations, based on a phase III trial.

The treatment has a manageable safety profile, with myelosuppression as the main concern, which can be effectively managed through monitoring and individualized dosing based on weight and platelet count.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib: A Review in First-Line Maintenance Therapy in Advanced Ovarian Cancer. Lee, A.[2022]

Niraparib significantly improves progression-free survival and other key outcomes in patients with recurrent, platinum-sensitive ovarian cancer, based on the phase III NOVA trial involving a randomized, double-blind, placebo-controlled design.

The treatment has a manageable safety profile, with most serious side effects being blood-related issues, which can be effectively managed through dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib: A Review in Ovarian Cancer. Heo, YA., Duggan, ST.[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, 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]

Citations

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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 ...

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PRIMA Clinical Study | Efficacy | ZEJULA (niraparib) for HCPs

ZEJULA was associated with long-term PFS benefits for patients with HRD-positive ovarian cancer.

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Efficacy of niraparib in patients with advanced ovarian cancer

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Niraparib improves outcomes in patients with newly ...

Women who received niraparib had a longer progression-free survival (amount of time until their cancer came back or got worse) than those who received a placebo

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Safety & Side Effects| ZEJULA (niraparib) for HCPs

An established safety and tolerability profile in 1L maintenance therapy of HRD-positive advanced ovarian cancer.

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10313963/

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Long-term safety data from the NOVA trial confirmed that, with appropriate and early dose modifications, niraparib is well tolerated. Keywords: ...

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accessdata.fda.gov/drugsatfda_docs/label/2020/208447s015s017lbledt.pdf

Zejula - accessdata.fda.gov

The most common adverse reactions of all grades in >10% of 1314 patients who received ZEJULA in the pooled PRIMA, NOVA and QUADRA trials were nausea (65%), ...

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Zejula | European Medicines Agency (EMA)

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cda-amc.ca

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The Safety of Niraparib in Ovarian Cancer

Clinical trials have shown that PARP inhibitors can cause hematological toxicity. A population-based, retrospective cohort study was conducted ...