The EndoBARR Trial (Endometrial Bevacizumab, Atezolizumab, Rucaparib)

Inclusion Criteria

• •1. Patients must have recurrent or persistent/progressive endometrial carcinoma, which is refractory to curative therapy or established treatments. Histologic confirmation of the original primary tumor is required. Stained slides of either the primary or recurrent tumor are required. If primary FFPE samples are not available, a biopsy demonstrating recurrent disease must be obtained. Pathologic Slides/Blocks will be reviewed at the primary site for confirmation.
• •2. Patients with the following histologic epithelial cell types are eligible: Endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, transitional cell carcinoma and uterine carcinosarcoma (MMT).
• •3. Patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma. Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a chemotherapy regimen. Patients may have had, but are not required to have received, a second chemotherapeutic regimen for recurrent disease.
• •4. All patients must have measurable disease, as defined by RECIST 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each target lesion must be ≥ 10 mm when measured by
• •CT or MRI. Lymph nodes must be \> 15 mm in short axis when measured by CT or MRI.
• •5. Patients may be enrolled if they do not have a target lesion (\>= 10 mm lesion or \>=15 mm lymph node), if they have measurable disease. This is defined by RECIST 1.1 as a suspicious lesion \<10mm or a lymph node \>=10mm but \<15mm.
• •6. Patients must have an EGOG Performance Status of 0, 1.
• •7. Recovery from effects of recent surgery, radiotherapy, or chemotherapy
• •8. Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated UTI).
• •9. Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration.
• •10. Any other prior therapy directed at the malignant tumor, including chemotherapy and immunologic agents, must be discontinued at least three weeks prior to first cycle of treatment.
• •11. Any prior radiation therapy must be completed at least four weeks prior to first cycle of treatment.
• •12. Prior hormonal therapy is allowed. There is no limit on the number of prior hormonal therapies allowed. Hormonal therapy will not be counted as a line of therapy for purposes of this trial.
• •13. Patients must have a urine protein of 2+ on dipstick. If dipstick is \>2+, 24-hour urine protein must be obtained and should be \< 1g for patient to be eligible.
• •14. Patients must have signed an approved informed consent and authorization permitting release of personal health information for study purposes.
• •15. Patients must meet pre-entry requirements, as specified in section 5.
• •16. Patients of childbearing potential must agree to use an accepted and effective nonhormonal method of contraception i.e., double-barrier method (e.g., condom plus diaphragm) from the time of signing the informed consent through six months after last dose of study drug.
• •17. Patients 18 years of age or greater.
• •18. Be willing to provide tissue from the primary surgical resection (paraffin block).
• •19. Must have laboratory values in the below ranges:
• •System Laboratory Value Endocrine Thyroid function testing (TSH) 0.350 - 5.500 ulU/mL (Or within institutional labarotory range).
• •Free T4/Total T3 If TSH is outside of laboratory range and subject is clinically euthyroid, enrollment may occur if Free T4/Total T3 are in normal range by local lab values Hematological
• •System Laboratory Value Absolute neutrophil count (ANC) ≥1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) Renal Serum creatinine OR Measured or calculateda creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR
• •≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR
• •≤ 5 X ULN for subjects with liver metastases Albumin \>2.5 mg/dL Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT)
• •Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• •≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants aCreatinine clearance should be calculated per institutional standard.