Newly diagnosed, histologically-confirmed stage III-IV endometrial carcinoma/carcinosarcoma with residual disease after surgery, either measurable or evaluable, and naïve to first line systemic anti-cancer treatment. Recurrent endometrial cancer patients if not yet treated for recurrent disease. MedDRA version: 20.0 Level: LLT Classification code 10014772 Term: Endometrioid adenocarcinoma recurrent
Conditions
Sponsors
IRCCS - Istituto di Ricerche Farmacologiche Mario Negri
Eligibility
Sex/Gender
All
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 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. 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 330 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 220
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. E-8. Treatment with systemic corticosteroids or other systemic immunosuppressive medications. E-9.History of autoimmune disease 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 . 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: a.Myocardial infarction or unstable angina within = 6 months of randomization, b.New York Heart Association (NYHA) = 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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy in terms of PFS and OS of first-line atezolizumab versus placebo in combination with carboplatin and paclitaxel in patients with advanced stage III/IV or recurrent endometrial cancer. ; Secondary Objective: 1.To determine the efficacy of atezolizumab as measured by: •Objective response rate (ORR) as assessed per RECIST v1.1 and median response duration •Time from randomization to second progression 2.To assess the safety and tolerability of the addition of atezolizumab. 3.To evaluate the effects of the addition of atezolizumab to carbo-taxol chemotherapy on Health-related Quality of Life (HRQoL) and patient function (physical, role). 4.To evaluate any treatment burden patients may experience in association with atezolizumab versus placebo. 5.To evaluate and compare between treatment arms patients' health status as measured by the EQ-5D-5L (including EQ VAS) to generate utility score. ; Primary end point(s): The study has two coprimary endpoints: OS and PFS. PFS is defined as the time from randomization to the date of first progression or death from any cause, whichever comes first. Progression will be established as the radiological disease progression according to RECIST 1.1 or death from any cause, whichever occurs first. OS is defined as the time from randomization until the date of death from any cause. ; Timepoint(s) of evaluation of this end point: Tumor assessments should be performed every 9 weeks during the chemotherapy treatment then every 12 weeks during the maintenance treatment (atezolizumab or placebo) for the first year from randomization. After the first year t | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Objective Response Rate (ORR), defined as the percentage of patients with an objective response as determined by RECIST 1.1 ; Timepoint(s) of evaluation of this end point: Tumor assessments should be performed every 9 weeks during the chemotherapy treatment then every 12 weeks during the maintenance treatment (atezolizumab or placebo) for the first year from randomization. After the first year the assessment during the maintenance phase should be performed every 6 months until progression. | — |
Countries
Austria, Germany, Poland, Spain, Switzerland, United Kingdom
Contacts
Public ContactElena Biagioli
IRCCS Istituto di Ricerche Farmacologiche Mario Negri
Outcome results
None listed