International study that compares a chemotherapy regimen with atezolizumab, paclitaxel and carboplatin versus a regimen with placebo, paclitaxel and carboplatin in patients affected by advanced or recurrent endometrial cancer

Phase 1

• Conditions: ewly diagnosed, histologically-confirmed stage III-IV endometrial carcinoma/carcinosarcoma with residual disease aftersurgery, either measurable or evaluable, and naïve to first line systemic anti-cancer treatment. Recurrent endometrial cancerpatients if not yet treated for recurrent disease.; MedDRA version: 21.1Level: LLTClassification code 10014772Term: Endometrioid adenocarcinoma recurrentSystem Organ Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code 10014776Term: Endometrioid adenocarcinoma stage IIISystem Organ Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code 10014777Term: Endometrioid adenocarcinoma stage IVSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-001072-37-AT
• Lead Sponsor: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-09-17
• Last Update Posted: 17 May 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 550

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 with a chemotherapy line for recurrent disease. Hormonal Treatment (including but not limited to progestins, tamoxifen, luteinizing hormone-releasing hormone agonists, aromatase Inhibitors) without chemotherapy is allowed.
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

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.Evidence of active tuberculosis.
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 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified