Bevacizumab and/or Niraparib in Patients With Recurrent Endometrial and/or Ovarian Cancer With ARID1A Mutation

Inclusion Criteria

• •Female subjects ≥ 18 years of age.
• •Histologically confirmed progressive or recurrent endometrial cancer or ovarian cancer with previously identified ARID1A tumor mutations.
• •a. Any ARID1A mutation is eligible and any CLIA Next generation sequencing test is allowable for eligibility.
• •Archival tumor tissue specimen available. Histological tissue specimen (tissue block or 8-10 unstained slides) must be available (specimen can be the sample at diagnosis or taken at relapse). Otherwise, patient must agree to have tumor biopsy to obtain sufficient tissue for histological assessment. If unable to be safely biopsied and patient desires enrollment, may be enrolled per MM discretion.
• •A subset of patients (15 ovarian samples and 15 endometrial samples) should agree to have optional tumor biopsy for translational studies assessment. If unable to be safely biopsied and patient desires enrollment, may be enrolled per medical monitor discretion. Tissue collection for the optional translational biopsies will continue until a total of 30 viable samples have been collected (15 endometrial and 15 ovarian). Patient agrees to have blood draw at pre-treatment and post-treatment (end of study) for translational studies assessment.
• •Patients who have progressed after ≥1 prior platinum containing 5.2 regimen.
• •Patient must agree to have blood draw at pre- and post-treatment for correlative studies.
• •Measurable disease by RECIST criteria v1.1.
• •ECOG performance status 0 or 1.
• •Patients should have no major existing co-morbidities or medical conditions that will preclude therapy in the view of the principal investigator.
• •Life expectancy \> 12 weeks.
• •Adequate bone marrow, hepatic and renal function as defined by the following values within 14 days prior to starting treatment:
• •1. Hemoglobin \>9 g/dL Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
• •2. Platelet count ≥ 100 x 109/L with no platelet transfusion in the past 28 days.
• •3. Creatinine clearance ≥50 mL/min (estimated using Cockcroft-Gault equation).
• •4. Total bilirubin ≤1.5 x institutional upper limit (ULN) (where bilirubin rise \> 1.5 x ULN due to Gilbert's syndrome a conjugated bilirubin ≤1.5 x ULN is required).
• •5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.5 x ULN if no demonstrable liver metastases or ≤5 times ULN if patient has documented liver metastases.
• •Women of child-bearing potential who are confirmed NOT to be pregnant. This should be evidenced by a negative urine or serum pregnancy test within 72 hours prior to start of trial treatment. Patients will be considered to be not of child-bearing potential if they are:
• •1. Post-menopausal - defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments, OR women under 50 years old who have been amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments and have serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and plasma oestradiol levels in the post-menopausal range for the institution.
• •2. Able to provide documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
• •3. Radiation or chemotherapy-induced oophorectomy or menopause with \> 1 year since last menses.
• •Patient is willing and able to comply with the protocol for the duration of the study. including undergoing treatment and scheduled visits and examinations.
• •Able to swallow, absorb, retain oral medication.
• •Able to provide written, informed consent.
• •Patients must have recovered from any effects of any major surgery and not have an open wound, active ulcer, or fistula.