Niraparib Maintenance Therapy for Endometrial Cancer

Recruiting in Palo Alto (17 mi)

+5 other locations

Overseen by Marina Frimer, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Northwell Health

Must be taking: Niraparib

Must not be taking: PARP inhibitors

Disqualifiers: Brain metastases, Hepatitis, MDS, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 3 Jurisdictions

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}

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.

Trial 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 (PARP Inhibitor)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Monter Cancer Institute New Hyde Park, NY

Imbert Cancer Center Northwell Health Bay Shore, NY

Greenlawn Cancer Institute, Northwell Health Greenlawn, NY

RJ Zuckerberg Cancer Hospital New Hyde Park, NY

More Trial Locations

Who Is Running the Clinical Trial?

Northwell Health Lead Sponsor

Tesaro, Inc. Industry Sponsor

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] Niraparib (Zejula™) is a poly(ADP-ribose) polymerase inhibitor recently approved by the US Food and Drug Administration for the maintenance treatment of patients with recurrent platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. The pivotal phase III clinical trial has shown improved progression-free survival in patients receiving niraparib compared with those receiving placebo.

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] To evaluate the efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer.

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

Niraparib: A Review in First-Line Maintenance Therapy in Advanced Ovarian Cancer. [2022] Niraparib (Zejula™) is a PARP inhibitor which is approved for maintenance therapy in adults with advanced ovarian cancer in complete or partial response to platinum-based chemotherapy. In a placebo-controlled phase III trial in patients with newly diagnosed advanced ovarian cancer, niraparib significantly extended progression free survival in two predefined populations, namely a patient population with altered homologous-recombination DNA repair pathways [i.e. homologous-recombination deficiency positive (HRd)] and the overall trial population. A prespecified exploratory subgroup analysis indicated that niraparib was also efficacious in patients who were homologous recombination deficiency negative or homologous recombination proficient (HRp). Niraparib has a manageable tolerability profile with myelosuppression as the main safety concern. Haematological reactions were managed with monitoring and dose reduction or interruption. A weight- and platelet count-based individualised dosage regimen introduced during the trial (and subsequently approved) appeared to improve haematological tolerability. Niraparib is a useful option for first-line maintenance therapy for advanced ovarian cancer in adults who responded to platinum-based chemotherapy, regardless of homologous-recombination deficiency status and is a promising option for HRp patients, for whom maintenance treatment options are limited.

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

Paclitaxel, Carboplatin, and Bevacizumab in Advanced and Recurrent Endometrial Carcinoma. [2018] The aim of this study was to evaluate the efficacy of adding bevacizumab to paclitaxel and carboplatin and as maintenance in a larger cohort of patients with advanced or recurrent endometrial carcinoma.

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] In the ENGOT-OV16/NOVA trial (ClinicalTrials.gov identifier: NCT01847274), maintenance therapy with niraparib, a poly(ADP-ribose) polymerase inhibitor, prolonged progression-free survival in patients with platinum-sensitive, recurrent ovarian cancer who had a response to their last platinum-based chemotherapy. The objective of the study was to assess the clinical benefit and patient-reported outcomes in patients who had a partial response (PR) and complete response (CR) to their last platinum-based therapy.

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

Safety and management of niraparib monotherapy in ovarian cancer clinical trials. [2023] Niraparib is a poly (ADP-ribose) polymerase inhibitor that has shown a significant improvement in progression-free survival irrespective of biomarker status in patients with advanced epithelial ovarian cancer. This review focuses on the adverse events associated with niraparib and their management to maintain efficacy of niraparib treatment and improve quality of life for patients. In five trials assessing efficacy of niraparib in patients with advanced epithelial ovarian cancer (PRIMA, NOVA, NORA, QUADRA, and PRIME), treatment-emergent adverse events of any grade were reported in nearly all patients (≥99%) receiving niraparib; the events were grade ≥3 in 51-74% of patients. Across all lines of therapy, treatment-emergent adverse events led to dose interruptions in 62-80% of patients receiving niraparib and dose reductions in 47-71%. Hematologic events were most frequently reported, including thrombocytopenia, anemia, and neutropenia. Common non-hematologic events included gastrointestinal events, which were generally low grade (

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] The primary objective of this study was to evaluate the safety of niraparib 300 mg/day in Japanese patients with platinum-sensitive, relapsed ovarian cancer in a maintenance setting.

8. France pubmed.ncbi.nlm.nih.gov

Niraparib: A Review in Ovarian Cancer. [2019] Niraparib (Zejula®), a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for the maintenance treatment of recurrent, epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in complete or partial response to platinum-based chemotherapy. Approval was based on the results of the randomized, double-blind, placebo-controlled phase III NOVA trial. In NOVA, niraparib significantly prolonged progression-free survival (primary endpoint), chemotherapy-free interval and time to first subsequent therapy compared with placebo in patients with recurrent, platinum-sensitive, high grade serous ovarian, fallopian tube or primary peritoneal cancer. The beneficial effects of niraparib were consistent regardless of BRCA mutation or homologous recombination deficiency (HRD) status. Niraparib had a manageable tolerability profile, with the majority of grade 3 or 4 adverse events being haematologic abnormalities (e.g. thrombocytopenia, anaemia, neutropenia). Adverse events were generally well managed with dose interruption or modification of niraparib. Current evidence suggests that niraparib is an effective new option with a manageable tolerability profile for the maintenance treatment of recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer in adults, with or without BRCA1/2 mutation or HRD.

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

Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. [2022] Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer.