Endometrial Cancer MedDRA version: 21.0 Level: PT Classification code 10014733 Term: Endometrial cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age =18 years at the time of screening and female. - Histologically confirmed diagnosis of epithelial endometrial carcinoma. All histologies, including carcinosarcomas, will be allowed. Sarcomas will not be allowed. - Patient must have endometrial cancer in one of the following categories: a Newly diagnosed Stage III disease (measurable disease per RECIST 1.1 following surgery or diagnostic biopsy), b) Newly diagnosed Stage IV disease (with or without disease following surgery or diagnostic biopsy) c) Recurrence of disease (measurable or non-measurable disease per RECIST 1.1) where the potential for cure by surgery alone or in combination is poor. - Naïve to first line systemic anti-cancer treatment. For patients with recurrent disease only, prior systemic anti-cancer treatment is allowed only if it was administered in the adjuvant setting (as part of the upfront/adjuvant anti-cancer treatment, which may be concurrent or followed with chemoradiation) and there is at least 12 months from date of last dose of chemotherapy administered to date of subsequent relapse. - FPPE tumor sample must be available for MMR evaluation. - Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of starting study treatment. 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 349 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 350
Exclusion criteria
Exclusion criteria: - History of leptomeningeal carcinomatosis. - Brain metastases or spinal cord compression. - Prior treatment with PARP inhibitors. - Prior immune-mediated therapy including other anti-CTLA-4, anti-PD-1, anti-PD-L1 or anti-PD-L2 antibodies, excluding therapeutic anticancer vaccines.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the efficacy of durvalumab in combination with platinum-based chemotherapy (paclitaxel and carboplatin) followed by maintenance durvalumab (Arm B) compared to platinum-based chemotherapy alone (Arm A) by assessment of progression free survival (PFS) for Arm B vs Arm A and PFS for Arm C vs Arm A, in patients with newly diagnosed advanced or recurrent endometrial cancer;Secondary Objective: -To determine the efficacy of durvalumab in combination with platinum-based chemotherapy (paclitaxel and carboplatin) followed by maintenance durvalumab (Arm B) or durvalumab with olaparib (Arm C) when compared to platinum-based chemotherapy alone (Arm A) in newly diagnosed advanced or recurrent endometrial cancer patients by assessment of: PFS2, OS, ORR, DoR, TFST, TSST and TDT. - To characterise the PK and immunogenicity of durvalumab and durvalumab in combination with olaparib. - To evaluate the safety and tolerability of durvalumab in combination with platinum-based chemotherapy followed by maintenance durvalumab or durvalumab with olaparib compared to platinum-based chemotherapy alone. - To determine effects on symptoms, functioning and overall health related quality of life (HRQoL) of durvalumab in combination with platinum-based chemotherapy followed by maintenance durvalumab or durvalumab with olaparib when compared to platinum-based chemotherapy alone;Primary end point(s): - PFS (per RECIST 1.1 as assessed by investigator) is defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression).;Timepoint(s) of evaluation of this end point: - randomisation until the date of objective disease progression or death | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - PFS2: Second progression-free survival is defined as the time from randomisation to the earliest of progression event subsequent to first subsequent therapy (assessed by the investigator per local standard clinical practice and may involve any of the following: objective radiological imaging, symptomatic progression), or death due to any cause. - OS: Overall survival is defined as the time from the date of randomisation until death due to any cause. - ORR: Objective response rate is the proportion of patients with measurable disease at baseline who have confirmed complete response (CR) or partial response (PR), as determined by the investigator at local site. - DoR: Duration of response is time from the date of first documented response (subsequently confirmed) until date of documented progression or death in the absence of disease progression, as determined by the investigator at local site.. - TFST: Time to first subsequent therapy or death is time from randomisation to the earlier of start date of the first subsequent anti-cancer therapy after discontinuation of randomised treatment or death due to any cause. - TSST: Time to second subsequent therapy or death is time from randomisation to the earlier of start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment or death due to any cause. - TDT: Time to study treatment discontinuation or death is time from randomisation to the earlier of the date of study treatment discontinuation or death. - Serum concentrations of durvalumab - Anti-drug antibodies (ADA) to durvalumab - Safety and tolerability will be evaluated in terms of AEs/serious AEs (SAEs), physical examination, vital signs including blood pressure, pulse, clinical laboratory including clinical chemistry/haematology parameters, and ECG;Timepoint(s) of evaluation of this end point: -PFS2: The earliest of progression event subsequent to first subsequent therapy, or death due t | — |
Countries
Australia, Belgium, Brazil, Canada, China, Colombia, Estonia, Germany, Greece, Hong Kong, Hungary, Israel, Japan, Korea, Republic of, Lithuania, Poland, Russian Federation, Singapore, Spain, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed