Endometrial cancer
Conditions
Interventions
placebo I.V. and chemotherapy and in maintenance
atezolizumab I.V. and chemotherapy and in maintenance
(Atezolizumab/placebo 1200mg dose will be delivered every 3 weeks prior to the carboplatin- pacli
Sponsors
Harano Kenichi
Eligibility
Sex/Gender
Female
Inclusion criteria
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 naive 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. In recurrent patients, 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, except for whole abdominal radiotherapy, 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 a. Haemoglobin >= 10.0 g/dL. b. Absolute neutrophil count (ANC) >= 1.5 x 109/L. c. Platelet count >= 100 x 109/L. d. Total bilirubin <= 1.5 x institutional upper limit of normal (ULN). e. 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. f. Serum creatinine <= 1.5 x institutional ULN
Exclusion criteria
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-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. 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, Sjogren`s syndrome, Guillain-Barre 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 . 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| OS,PFS | — |
Secondary
| Measure | Time frame |
|---|---|
| - Objective Response Rate (ORR), defined as the percentage of patients with an objective response as determined by RECIST 1.1; - Duration of response, defined as the time from the date of first documentation of response (complete response (CR) or partial response (PR), whichever occurs first) to the date of documented PD or death; - Second Progression Free Survival (PFS2), defined as the time from randomization to the earliest of the progression event subsequent to that used for the primary variable PFS, or date of death. The date of second progression will be recorded by the investigator and defined according to local standard clinical practice; - Change from baseline in quality of life scores evaluated on subscales and total scores using the EORTC QLQ-C30 and QLQ-EN24; - Proportion of patients reporting each response option at each assessment timepoint by treatment arm for item GP5 from the FACT-G instrument - Health utility scores of the EuroQoL 5 Dimension, 5 Level Questionnaire (EQ-5D-5L). European Quality of Life Visual Analogue Scale (EQ VAS) | — |
Countries
Australia, Austria, Germany, Italy, Japan, Korea, NewZeland, Spain, Switzerland, Taiwan, UK
Contacts
Public ContactYuji Matsuyama
Japan Gynecologic Oncology Group
Outcome results
None listed