Atezolizumab Trial in Endometrial cancer.

Exclusion Criteria36

• Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS) of the breast. Patients with a history of localized malignancy diagnosed over 5 years ago may be eligible provided they completed their adjuvant systemic therapy prior to randomization and that the patient remains free of recurrent or metastatic disease
• Patients with uterine leiomyosarcoma
• Major surgery within 4 weeks of starting study treatment or patients who have not completely recovered from the effects of any major surgery
• Previous allogeneic bone marrow transplant or previous solid organ transplantation
• Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement therapy is permitted).
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies,
• anti-PD1, or anti-PDL1 therapeutic antibodies or anti-CTLA4
• Treatment with systemic immunostimulatory agents (including but not limited to interferon-alpha (IFN-a) and interleukin-2 (IL-2) within 4 weeks or five half-lives of the drug (whichever is shorter) prior to Cycle 1, Day 1
• Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents) within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for systemic
• immunosuppressive medications during the trial. However, please note that the use of inhaled corticosteroids for chronic obstructive pulmonary disease or for asthma is allowed, as well as the use of mineralocorticoids (e.g., fludrocortisones) and low-dose supplemental corticosteroids for adrenocortical insufficiency and for patients with orthostatic hypotension. The use of corticosteroids as premedication for paclitaxel-based regimen is allowed)
• History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, GuillainBarré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis [please note: patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible; patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible; history of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, Organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia) is permitted]
• Immunocompromised patients, e.g. patients who are known to be serologically
• positive for human immunodeficiency virus (HIV)
• Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C
• a. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive total hepatitis B core antibody [HBcAb]) are eligible only if hepatitis B virus (HBV) DNA is negative. The HBV DNA test will be performed only for patients who have a positive total HBcAb test
• b. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. The HCV RNA test will be performed only for patients who have a positive HCV antibody test
• Evidence of active tuberculosis
• Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1
• Administration of a live, attenuated vaccine within 4 weeks prior to Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study. Influenza vaccination should be given during influenza season only (example approximately October to March in the Northern Hemisphere). Patients must not receive live, attenuated influenza vaccine.
• Clinically significant (e.g. active) cardiovascular disease, including:
• a. Myocardial infarction or unstable angina within less than or equal to 6 months of randomization,
• b. New York Heart Association (NYHA) greater than or equal to grade 2 congestive heart failure (CHF),
• c. Poorly controlled cardiac arrhythmia despite medication (patients with rate controlled atrial fibrillation are eligible),
• d. Peripheral vascular disease greater than or equal to grade 3 (e.g. symptomatic and interfering with activities of daily living [ADL] requiring repair or revision)
• Resting ECG with QTc greater than 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
• History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI
• of the brain is mandatory (within 4 weeks prior to randomization) in case of suspected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to randomization) in any case of suspected central nervous system (CNS) involvement
• History or evidence upon neurological examination of central nervous system (CNS)
• disease, unless asymptomatic and adequately treated with standard medical therapy
• Evidence of any other disease, metabolic dysfunction, physical examination finding
• or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment related complications
• Women of childbearing potential (less than 2 years after last menstruation) not willing to use highly-effective means of contraception
• Pregnant or lactating women
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation
• Known hypersensitivity reaction or allergy to drugs chemically related to carboplatin, paclitaxel, or their excipients that contraindicates the subject’s participation