Long-term Niraparib for Cancer

Recruiting at 29 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: GlaxoSmithKline

Must be taking: Niraparib

Disqualifiers: Pregnancy, Breastfeeding, Unresolved toxicities, 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

26 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial provides continued access to niraparib for patients already receiving it in certain studies and aims to understand its ongoing safety. Niraparib helps stop cancer cells from repairing their DNA, which can kill the cancer. Niraparib is approved for use in ovarian cancer patients who respond to specific 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. However, since this study is for participants already on niraparib, it seems likely you can continue with your current treatment.

What data supports the effectiveness of the drug Niraparib for cancer?

Research shows that Niraparib, a drug used for maintenance therapy in ovarian cancer, significantly extends the time patients live without their cancer getting worse compared to those who do not take it. It is effective for patients with certain genetic profiles and even those without, making it a promising option for many. ^{1 2 3 4 5}

Is niraparib generally safe for human use?

Niraparib has been associated with some side effects, including blood-related issues like low platelet counts (thrombocytopenia), low red blood cell counts (anemia), and low white blood cell counts (neutropenia). Other common side effects include digestive issues and nerve problems. These side effects are often managed by adjusting the dose or taking breaks from the medication. ^{1 2 6 7 8}

How is the drug Niraparib unique in treating cancer?

Niraparib is unique because it is a PARP inhibitor (a type of drug that blocks an enzyme involved in repairing damaged DNA) used as maintenance therapy for ovarian cancer, extending progression-free survival in patients regardless of their DNA repair status. It is taken orally and has a personalized dosing regimen based on weight and platelet count to improve safety. ^{1 2 5 9 10}

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

This trial is for individuals already participating in certain GlaxoSmithKline/TESARO-sponsored studies of Niraparib, who are seeing benefits from the treatment. They must be able to follow the study plan and agree to use effective contraception if they can have children. Pregnant or breastfeeding individuals, those planning to conceive, or with unresolved toxicities from previous Niraparib treatments cannot join.

Inclusion Criteria

I am currently seeing positive results from my niraparib treatment.

I am currently on niraparib treatment in a GlaxoSmithKline/TESARO study.

You are willing and able to comply with study procedures.

Exclusion Criteria

Participant is breastfeeding or is expecting to breastfeed within 30 days of receiving the final dose of study drug (women should not breastfeed or store breastmilk for use during niraparib treatment and for 30 days after receiving the final dose of study treatment).

I was taken off niraparib treatment for any reason.

Participant is pregnant or is expecting to conceive children while receiving study drug or for up to 180 days after the last dose of study drug.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Long-term Treatment Extension

Participants receive niraparib once a day, continuously throughout each 90-day cycle until disease progression, unacceptable toxicity, or other discontinuation criteria are met.

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Niraparib

Trial Overview The trial provides continued access to Niraparib for participants benefiting from it in prior related studies. It aims to gather more data on the long-term safety of this cancer medication when used by patients with tumors, breast cancer, or ovarian tumors.

Participant Groups

Group I: Participants receiving niraparib Experimental Treatment 1 Intervention

Participants will receive niraparib once a day, continuously throughout each 90-day cycle until one of the following occurs: disease progression, unacceptable toxicity, initiation of new anticancer therapy that was not part of the parent study, withdrawal of consent, discontinuation at the discretion of the Investigator, noncompliance with protocol, death, or discontinuation for any other reason. The doses provided in this long-term treatment extension study will be those defined in the parent study for each enrolled participant. The starting dose of niraparib will be the same as the assigned dose and regimen that were given in the parent study.

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?

GlaxoSmithKline

Lead 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

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 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 has been approved by the FDA for patients with complete or partial response to first-line platinum-based chemotherapy, regardless of their BRCAm or HRD status, expanding treatment options for more patients.

Olaparib, in combination with bevacizumab, has also received FDA approval for patients with epithelial ovarian cancer, indicating that PARP inhibitors are now beneficial not only for BRCAm and HRD-deficient patients but also for those with HRD-proficient tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PARP inhibitors in the treatment of ovarian cancer: a review. Washington, CR., Moore, KN.[2023]

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 (Zejula) is effective for treating recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, providing a targeted therapy option for these specific cancer types.

Ocrelizumab (Ocrevus) has shown efficacy in managing both relapsing and primary progressive multiple sclerosis, while dupilumab (Dupixent) is effective for patients with moderate-to-severe atopic dermatitis, highlighting its role in managing chronic inflammatory skin conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical Approval Update. Choy, M.[2020]

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]

Niraparib, administered at doses of 200 mg and 300 mg daily, was found to be tolerable in Japanese patients with advanced solid tumors, with only one case of dose-limiting toxicity observed.

The study demonstrated a favorable pharmacokinetic profile for niraparib, with dose-proportional increases in drug levels and some patients showing a partial response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety, tolerability and pharmacokinetics of niraparib in Japanese patients with solid tumours: results of a phase I dose-escalation study. Yonemori, K., Shimizu, T., Kondo, S., 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, 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]

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. France pubmed.ncbi.nlm.nih.gov

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

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

PARP inhibitors in the treatment of ovarian cancer: a review. [2023]

4. Korea (South) 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. [2021]

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

Pharmaceutical Approval Update. [2020]

6. England pubmed.ncbi.nlm.nih.gov

A real-world pharmacovigilance study of FDA adverse event reporting system (FAERS) events for niraparib. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Safety and management of niraparib monotherapy in ovarian cancer clinical trials. [2023]

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

The safety, tolerability and pharmacokinetics of niraparib in Japanese patients with solid tumours: results of a phase I dose-escalation study. [2021]

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

Identifying the need to refine the potential patient risk factors for niraparib-induced thrombocytopenia. [2019]

10. United States 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. [2021]