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Atezolizumab Trial in Endometrial Cancer - AtTEnd
Bu çalışma, ilerlemiş veya nüks etmiş endometriyum kanseri (endometrial cancer) olan hastalarda kemoterapiye (Paclitaxel ve Carboplatin) eklenen Atezolizumab ilacını plaseboyla karşılaştırıyor. Katılım için yeni tanı almış, ameliyat sonrası hastalığı devam eden veya ameliyata uygun olmayan evre III-IV hastalar ile daha önce tedavi görmemiş nüks endometriyum kanseri hastaları uygundur. Faz 3 aşamasında yürütülmüş ve tamamlanmıştır.
Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.
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Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.
Inclusion Criteria: I-1. Newly diagnosed, histologically-confirmed with residual disease after surgery either measurable or evaluable, or inoperable stage III-IV endometrial carcinoma/carcinosarcoma, after diagnostic biopsy, and naïve to first line systemic anti-cancer treatment. Recurrent endometrial cancer patients if not yet treated for recurrent disease. I-2. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 I-3. Age ≥ 18 years I-4. Only one prior line of systemic platinum-based regimen is permitted if the platinum-free interval ≥ 6 months. Such prior line is the up-front/adjuvant treatment which can be concurrent chemoradiation or concurrent chemoradiation followed by chemotherapy or only chemotherapy. I-5. Patients with history of primary breast cancer may be eligible provided they completed their definitive anticancer treatment more than 3 years ago and they remain breast cancer disease free prior to start of study treatment. I-6. Previous pelvic and outside pelvis radiation is allowed if completed more than 6 weeks ago. I-7. Signed informed consent and ability to comply with treatment and follow-up. I-8. Representative FFPE tumor sample or, only if unfeasible, at least 20 unstained slides from initial surgery or from diagnostic biopsy, in case surgery was not performed, available and sent to central laboratory for Micro Satellite (MS) determination prior to randomization. I-9. Patients must have normal organ and bone marrow function : 1. Haemoglobin ≥ 10.0 g/dL. 2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. 3. Platelet count ≥ 100 x 109/L. 4. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). 5. Aspartate aminotransferase /Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT)) and Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) ≤ 2.5 x ULN, unless liver metastases are present in which case they must be ≤ 5 x ULN. 6. Serum creatinine ≤ 1.5 x institutional ULN Exclusion Criteria: E-1. 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. E-2. Patients with uterine leiomyosarcoma . E-3. Major surgery within 4 weeks of starting study treatment or patients who have not completely recovered from the effects of any major surgery. E-4. Previous allogeneic bone marrow transplant or previous solid organ transplantation. E-5. 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). E-6. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD1, or anti-PDL1 therapeutic antibodies or anti-CTLA4 . E-7. Treatment with systemic immunostimulatory agents (including but not limited to interferon-alpha (IFN-α) and interleukin-2 (IL-2) within 4 weeks or five half-lives of the drug (whichever is shorter) prior to Cycle 1, Day 1. E-8. 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). E-9. 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 anti-phospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis \[please note: patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible; patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible; history of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia) is permitted\]. E-10. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV). E-11. Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C . 1. 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. 2. 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. E-12. Active tuberculosis (all patients will have tuberculin \[PPD\] skin test or Interferon-Gamma Releasing Assay \[IGRA\] done locally prior to inclusion to study) E-13. Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1 E-14. 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. E-15. Clinically significant (e.g. active) cardiovascular disease, including: 1. Myocardial infarction or unstable angina within ≤ 6 months of randomization, 2. New York Heart Association (NYHA) ≥ grade 2 congestive heart failure (CHF), 3. Poorly controlled cardiac arrhythmia despite medication (patients with rate controlled atrial fibrillation are eligible), 4. Peripheral vascular disease grade ≥ 3 (e.g. symptomatic and interfering with activities of daily living \[ADL\] requiring repair or revision) E-16. Resting ECG with QTc \> 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome. E-17. 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 . E-18. History or evidence upon neurological examination of central nervous system (CNS) disease, unless asymptomatic and adequately treated with standard medical therapy. E-19. 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. E-20. Women of childbearing potential (\<2 years after last menstruation) not willing to use highly-effective means of contraception. E-21. Pregnant or lactating women. E-22. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins. E-23. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation. E-24. Known hypersensitivity reaction or allergy to drugs chemically related to carboplatin, paclitaxel, or their excipients that contraindicates the subject's participation