Niraparib Maintenance Therapy for Endometrial Cancer

No longer recruiting at 6 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of Niraparib (also known as Zejula) for individuals with advanced uterine serous carcinoma, a type of endometrial cancer. Researchers aim to determine if Niraparib can prevent cancer recurrence after initial treatment and assess its safety. Women with this specific cancer type who have responded to prior chemotherapy may qualify for the trial. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that Niraparib is generally well-tolerated by patients. It has been successfully used to treat conditions like ovarian cancer, which are similar to uterine serous carcinoma. In these studies, patients experienced manageable side effects. Common side effects included tiredness, nausea, and low blood cell counts. While these might sound concerning, they are typical for many cancer treatments and are closely monitored by doctors.

Niraparib already has FDA approval for other types of cancer, which adds confidence in its safety. The current study aims to confirm its safety specifically for uterine serous carcinoma. This trial is in an early phase, so researchers are still collecting detailed safety information. However, existing evidence suggests that Niraparib may be a safe and promising option for people with this type of cancer. ^{1 2 3 4 5}

Why are researchers excited about this possible treatment for endometrial cancer?

Niraparib is unique because it targets a specific weakness in cancer cells, known as the PARP (poly ADP-ribose polymerase) pathway. Unlike other treatments for endometrial cancer, such as chemotherapy or hormonal therapies, which broadly attack rapidly dividing cells, niraparib specifically disrupts the DNA repair process in cancer cells, leading to their death. Researchers are excited about niraparib because its targeted approach could lead to more effective treatment outcomes with potentially fewer side effects, offering new hope for patients with uterine serous carcinoma.

What evidence suggests that Niraparib might be an effective treatment for uterine serous carcinoma?

Studies have shown that Niraparib, a PARP inhibitor, can help treat uterine serous carcinoma (USC). Research suggests that patients with USC share many similarities with those who have serous ovarian cancer, where Niraparib has proven beneficial. In this trial, participants will receive Niraparib as ongoing treatment, which has been linked to better outcomes for patients with advanced or recurring USC that responds to platinum-based chemotherapy. Early results indicate that Niraparib is generally well-tolerated and effective in these patients, making it a promising option for those facing this aggressive form of endometrial cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Marina Frimer, MD

Principal Investigator

Northwell Health

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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 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]

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 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 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, 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04080284

Trial of Maintenance With Niraparib- Uterine Serous ... The objective of this study is to evaluate the efficacy of maintenance Niraparib regimen in patients with advanced or platinum sensitive recurrent uterine ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12142135/

Maintenance with niraparib in patients with stage III ... Uterine serous carcinoma (USC) accounts for 40% of endometrial cancer-related deaths. The standard of care for stages III and IV USC yields a 20 ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-02518

Trial of Maintenance With Niraparib- Uterine Serous ... The investigators hypothesize that Niraparib maintenance will be a well-tolerated treatment and show significant response in patients with uterine serous ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04080284?term=serous&cond=endometrial%20cancer&viewType=Table&checkSpell=&rank=3

Trial of Maintenance With Niraparib- Uterine Serous ... The objective of this study is to evaluate the efficacy of maintenance Niraparib regimen in patients with advanced or platinum sensitive recurrent uterine ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090825822015529

Phase II trial of maintenance niraparib in patients with ... This study aims to determine the efficacy of Niraparib in women with advanced or platinum-sensitive recurrent USC. We also aim to describe the safety profile ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04716686?term=serous&cond=endometrial%20cancer&viewType=Table&checkSpell=&rank=4

Niraparib Monotherapy as Maintain and Recurrent ... Also called a data safety and monitoring board, or DSMB. Early Phase 1 (formerly listed as Phase 0). A phase of research used to describe exploratory trials ...

7. centerwatch.com centerwatch.com/clinical-trials/listings/condition/1056/uterine-serous-carcinoma

Uterine Serous Carcinoma Clinical Research Trials Uterine Serous Carcinoma is a rare and aggressive type of endometrial cancer. It accounts for only 10-15% of all endometrial cancer cases.