Niraparib Maintenance Therapy for Endometrial Cancer

Recruiting at 5 trial locations

Overseen By Marina Frimer, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Northwell Health

Must be taking: Niraparib

Must not be taking: PARP inhibitors

Disqualifiers: Brain metastases, Hepatitis, MDS, 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: 3

Duration: 1 year

45 Participants Needed

Trial Summary

What is the purpose of this trial?

Uterine serous carcinoma (USC) accounts for up to 40% of endometrial cancer-related deaths. Patients with USC share many genomic and clinical characteristics with patients who has serous ovarian cancer. The objective of this study is to evaluate the efficacy of maintenance Niraparib regimen in patients with advanced or platinum sensitive recurrent uterine serous carcinoma. Additionally, the investigators aim to further describe the safety of this regimen. The investigators hypothesize that Niraparib maintenance will be a well-tolerated treatment and show significant response in patients with uterine serous carcinoma.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you can continue taking corticosteroids if your dose is stable for at least 4 weeks before starting the trial.

What data supports the idea that Niraparib Maintenance Therapy for Endometrial Cancer is an effective treatment?

The available research shows that Niraparib is effective in treating ovarian cancer, as it significantly extends the time patients live without the disease getting worse. However, there is no specific data provided about its effectiveness for endometrial cancer. Other treatments for endometrial cancer, like the combination of paclitaxel, carboplatin, and bevacizumab, have been studied, but Niraparib's effectiveness for endometrial cancer is not directly supported by the information available. ^{1 2 3 4 5}

What safety data is available for Niraparib treatment?

Niraparib, also known as Zejula, has been evaluated in several clinical trials primarily for ovarian cancer. Safety data indicates that nearly all patients experience treatment-emergent adverse events, with 51-74% experiencing grade ≥3 events. Common adverse events include hematologic issues like thrombocytopenia, anemia, and neutropenia, as well as gastrointestinal events. These adverse events often lead to dose interruptions or reductions. A weight- and platelet count-based individualized dosage regimen has been introduced to improve hematological tolerability. ^{1 2 3 6 7}

Is the drug Niraparib a promising treatment for endometrial cancer?

Niraparib is a promising drug because it has been shown to help patients with ovarian cancer live longer without the disease getting worse. It works by targeting specific pathways in cancer cells, and it has been effective in patients regardless of certain genetic factors. This suggests it could be a valuable option for treating endometrial cancer as well. ^{1 2 3 8 9}

Research Team

Marina Frimer, MD

Principal Investigator

Northwell Health

Eligibility Criteria

This trial is for women aged 18 or older with advanced stage uterine serous carcinoma (USC) who have responded to chemotherapy. They must not be breastfeeding, agree to contraception if of childbearing potential, and have good organ function. Those with persistent severe blood disorders from past treatments, recent major surgery, uncontrolled medical conditions, active infections, or prior PARP inhibitor treatment are excluded.

Inclusion Criteria

My cancer is a type called Uterine Serous Carcinoma.

I am a woman aged 18 or older.

My tumor has responded to at least 3 cycles of chemotherapy.

Exclusion Criteria

I have never been diagnosed with MDS or AML.

You are allergic to the ingredients in Niraparib.

I haven't had major surgery in the last 3 weeks or still recovering from one.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral Niraparib as maintenance therapy for uterine serous carcinoma

1 year

Visits every 3 months for quality of life assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Long-term follow-up

Participants are monitored for overall survival and mutational burden

5 years

Treatment Details

Interventions

• Niraparib

Trial Overview The study tests the effectiveness and safety of Niraparib as a maintenance therapy in patients with USC who've had a positive response to platinum-based chemotherapy. The goal is to see if taking Niraparib after chemo helps control cancer growth better than the current standard care.

Participant Groups

Group I: Niraparib Experimental Treatment 1 Intervention

Oral niraparib -Cohort - Uterine serous carcinoma

Who Is Running the Clinical Trial?

Northwell Health

Lead Sponsor

Trials

481

Recruited

470,000+

Tesaro, Inc.

Industry Sponsor

Trials

57

Recruited

10,600+

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]

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]

In a study involving 27 patients with advanced or recurrent endometrial carcinoma, the combination of bevacizumab with paclitaxel and carboplatin showed a high response rate of 82.8% in first-line therapy, indicating its efficacy in treating this cancer.

The median progression-free survival was 20 months and median overall survival was 56 months, suggesting that this treatment regimen can significantly extend the lives of patients with advanced endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel, Carboplatin, and Bevacizumab in Advanced and Recurrent Endometrial Carcinoma. Rose, PG., Ali, S., Moslemi-Kebria, M., et al.[2018]

In the ENGOT-OV16/NOVA trial involving 553 patients with platinum-sensitive recurrent ovarian cancer, maintenance therapy with niraparib significantly improved progression-free survival compared to placebo for both patients with germline BRCA mutations and those without.

The treatment was found to have manageable side effects, and there were no significant differences in patient-reported outcomes between those receiving niraparib and those on placebo, indicating that niraparib is a safe and effective option for maintaining treatment benefits after platinum-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial. Del Campo, JM., Matulonis, UA., Malander, S., et al.[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]

In a Phase 2 study involving 19 Japanese patients with platinum-sensitive, relapsed ovarian cancer, niraparib at a dose of 300 mg/day was found to have a safety profile consistent with previous studies, with 31.6% of patients experiencing grade 3 or 4 thrombocytopenia-related events within 30 days of treatment.

The overall safety profile of niraparib was deemed acceptable, with common treatment-emergent adverse events including nausea and decreased blood cell counts, but no significant improvements in tumor response were observed in the small cohort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 single-arm study on the safety of maintenance niraparib in Japanese patients with platinum-sensitive relapsed ovarian cancer. Takehara, K., Matsumoto, T., Hamanishi, J., et al.[2021]

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 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]

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. 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]

3. France pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Paclitaxel, Carboplatin, and Bevacizumab in Advanced and Recurrent Endometrial Carcinoma. [2018]

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

Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial. [2020]

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

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

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Phase 2 single-arm study on the safety of maintenance niraparib in Japanese patients with platinum-sensitive relapsed ovarian cancer. [2021]

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

Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. [2022]

9. France pubmed.ncbi.nlm.nih.gov

Niraparib: A Review in Ovarian Cancer. [2019]