The study will first enroll patients with recurrent endometrial cancer regardless of PTEN status. If this patient population does not meet the criteria for clinical efficacy, retrospective analysis of PTEN status will be done and the study will potentially continue with a focus on participants with PTEN loss.

Participants will be screened for eligibility by standard safety tests and procedures within 28 days of the start of the study drug. Tests and procedures done for research purposes only during this time include archival tumor tissue collection for biomarker/genetic research including PTEN analysis, and blood sample collection for analysis in the even the participant develops myelodysplastic syndrome) MDS or acute myeloid leukemia (AML).

Eligible participants will take niraparib capsules or tablets by mouth, at 300 mg, once a day, every day of every 28 day cycle.

While receiving the study treatment, participants will be asked to visit the study site on Days 1, 8, 15, and 21 of Cycle 1, Days 1 and 15 of Cycle 2, and Day 1 of Cycle 3 and future cycles for safety tests and procedures. If, at any time, participants develop (or is suspected to have developed) MDS/AML, a mandatory bone marrow aspirate/biopsy will be done for testing to confirm diagnosis.

When participants are taken off the study treatment permanently, they will be asked to return to the study site for an End of Study Treatment visit to have tests and procedures done for safety purposes.

Participants who are taken off the study treatment for any reason other than disease progression will continue to have radiological assessments every 12 weeks until disease progression. Participants will continue to be followed up for side effects weekly in the first 4 weeks, then monthly until resolution.

Inclusion Criteria:

• Histologically confirmed epithelial endometrial cancer. All histological subtypes are allowed except for endometrial sarcoma, carcinosarcoma, clear cell, mixed and adenosquamous tumors.
• Patients must have radiographic evidence of disease progression following the most recent line of treatment.
• Patients must have previously received at least one line of platinum-based chemotherapy. Prior hormonal and immunotherapy are allowed. There is no restriction on the total number prior lines of therapy.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥10 mm with CT scan, MRI, or calipers by clinical exam, and ≥15mm for nodal lesions. Areas of previous radiation may not serve as measurable disease unless there is evidence of progression post radiation.
• Patients must have archival tumor sample available for PTEN analysis. If archival tissue is not available, the patient will have the option to undergo tumor biopsy.
• Eastern Cooperative Group (ECOG) performance status ≤ 2.
• Life expectancy of greater than 12 weeks.
• Within 7 days of the proposed start of treatment, patients must have normal organ and marrow function.

Exclusion Criteria:

• Chemotherapy or biologic agents received within 4 weeks of starting study treatment.
• Hormonal therapy within 2 weeks of starting study treatment.
• Pelvic radiotherapy (as treatment of primary disease) within 4 weeks, or palliative radiotherapy encompassing >20% of the bone marrow within 1 week of starting study treatment.
• Previous treatment with a PARP inhibitor, or any other targeted therapy directed against the homologous recombination pathway.
• Patients who are receiving any other investigational agents.
• Ongoing ≥ Grade 2 toxicities related to prior cancer therapy, with the exceptions of alopecia, neuropathy, lymphopenia and skin depigmentation.
• Received transfusion (platelets or red blood cells) ≤4 weeks of the first dose of study treatment.
• Major surgery within 4 weeks of registration or ongoing clinically significant post-surgical complications. Study biopsy is not considered major surgery.
• Known brain metastases, except if stable for greater than 28 days following definitive treatment. The patient must have no new or progressive signs or symptoms related to the CNS disease and must be either off or taking a stable dose of corticosteroids. A scan to confirm the absence of brain metastases is not required.
• History of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML).
• History of bowel obstruction within 3 months, or other reason preventing effective oral administration of medication.
• Immunocompromised patients e.g. Human Immunodeficiency Virus (HIV) requiring treatment or active Hepatitis B or C. Prior splenectomy is allowed.
• Uncontrolled inter-current illness.
• History of other malignancy ≤ 3 years prior to registration with the exceptions of a) cone-biopsied in situ carcinoma of the cervix uteri; b) basal or squamous cell carcinoma of the skin. All second malignancies in this context should be discussed with the Principal Investigator.