A Randomised, Multicentre, Double-blind, Placebo-controlled, Phase III Study of First-line Carboplatin and Paclitaxel in Combination With Durvalumab, Followed by Maintenance Durvalumab With or Without Olaparib in Patients With Newly Diagnosed Advanced or Recurrent Endometrial Cancer (DUO-E)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 805
- 试验地点
- 201
- 主要终点
- Progression-free Survival (PFS) According to RECIST 1.1, Based on Investigator Assessments
研究概览
简要总结
A study to assess the efficacy and safety of durvalumab in combination with platinum-based chemotherapy (paclitaxel + carboplatin) followed by maintenance durvalumab with or without olaparib for patients with newly diagnosed advanced or recurrent endometrial cancer.
详细描述
This Phase III study will assess the efficacy and safety of durvalumab in combination with platinum-based chemotherapy (paclitaxel + carboplatin) followed by maintenance durvalumab with or without olaparib for patients with newly diagnosed advanced or recurrent endometrial cancer.
Target patient population: Adult female patients with histologically confirmed diagnosis of epithelial endometrial carcinoma (excluding sarcomas): newly diagnosed Stage III, newly diagnosed Stage IV, or recurrent endometrial cancer
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 150 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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:
- •Newly diagnosed Stage III disease (measurable disease per RECIST 1.1 following surgery or diagnostic biopsy),
- •Newly diagnosed Stage IV disease (with or without disease following surgery or diagnostic biopsy)
- •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 and there is at least 12 months from date of last dose of systemic anti-cancer treatment 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.
排除标准
- •History of leptomeningeal carcinomatosis.
- •Brain metastases or spinal cord compression.
- •Prior treatment with PARP inhibitors.
- •Any prior exposure to immune-mediated therapy, including (but not limited to) other anti CTLA-4, anti-PD-1, anti-PD-L1, or anti-programmed-cell-death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.
研究组 & 干预措施
Arm A (control)
Platinum-based chemotherapy and durvalumab placebo followed by maintenance durvalumab placebo and olaparib placebo (tablets).
干预措施: Carboplatin (Drug)
Arm B (durvalumab+placebo)
Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib placebo
干预措施: olaparib placebo (Drug)
Arm A (control)
Platinum-based chemotherapy and durvalumab placebo followed by maintenance durvalumab placebo and olaparib placebo (tablets).
干预措施: durvalumab placebo (Drug)
Arm B (durvalumab+placebo)
Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib placebo
干预措施: durvalumab (Biological)
Arm A (control)
Platinum-based chemotherapy and durvalumab placebo followed by maintenance durvalumab placebo and olaparib placebo (tablets).
干预措施: olaparib placebo (Drug)
Arm C (durvalumab+olaparib)
Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib.
干预措施: durvalumab (Biological)
Arm A (control)
Platinum-based chemotherapy and durvalumab placebo followed by maintenance durvalumab placebo and olaparib placebo (tablets).
干预措施: Paclitaxel (Drug)
Arm B (durvalumab+placebo)
Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib placebo
干预措施: Carboplatin (Drug)
Arm B (durvalumab+placebo)
Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib placebo
干预措施: Paclitaxel (Drug)
Arm C (durvalumab+olaparib)
Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib.
干预措施: olaparib (Drug)
Arm C (durvalumab+olaparib)
Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib.
干预措施: Carboplatin (Drug)
Arm C (durvalumab+olaparib)
Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Progression-free Survival (PFS) According to RECIST 1.1, Based on Investigator Assessments
时间窗: At baseline, every 9 weeks (wks) up to 18 wks, then every 12 wks until objective radiological disease progression. Assessed until 12 Apr 2023 DCO (08 Jul 2024 DCO for China cohort), up to 50 months
To demonstrate the efficacy of durvalumab in combination with platinum-based chemotherapy (paclitaxel and carboplatin) followed by maintenance durvalumab or durvalumab with olaparib when compared to platinum-based chemotherapy by assessment of PFS (using investigator assessment according to Response Evaluation Criteria in Solid Tumours version 1.1 \[RECIST 1.1\]) in patients with newly diagnosed advanced or recurrent endometrial cancer
次要结局
- Overall Survival (OS) Analysis(Survival assessed every 2 months after RECIST defined radiological progression; assessed through study completion, up to 83 months)
- Time From Randomisation to Second Progression or Death (PFS2) Based on Local Standard Clinical Practice(At baseline, every 9 to 18 wks, then every 12 wks until objective radiological disease progression. Assessments then per local practice every 12 wks until second progression. Assessed until 12Apr2023 DCO (08Jul2024 DCO for China cohort), up to 50 months)
- Objective Response Rate (ORR) Based on Investigator Assessment(At baseline, every 9 to 18 wks, then every 12 wks until objective radiological disease progression. Assessed until 12 Apr 2023 DCO (08 Jul 2024 DCO for China cohort), up to 50 months)
- Duration of Response (DoR) Based on Investigator Assessment(At baseline, every 9 wks up to 18 wks, then every 12 wks until objective radiological disease progression. Assessed until 12 Apr 2023 DCO, up to 35 months)
- Time From Randomisation to First Subsequent Therapy or Death (TFST)(Time elapsed from randomisation to first subsequent therapy or death. Assessed every 12 wks following treatment discontinuation, through study completion (up to 83 months))
- Time From Randomisation to Second Subsequent Therapy or Death (TSST)(Time elapsed from randomisation to second subsequent therapy or death. Assessed every 12 wks following treatment discontinuation, through study completion (up to 83 months))
- Time From Randomisation to Discontinuation of Treatment or Death (TDT)(Time elapsed from randomisation to study treatment discontinuation or death. Assessed through study completion, up to 83 months)
- Serum Concentration of Durvalumab(PK sampling performed on Day 85 pre-dose, Day 183 pre-dose, and 3 months after study treatment discontinuation (up to 36 months))
- Anti-drug Antibodies (ADA) to Durvalumab(Immunogenicity sampling performed on Day 1 pre-dose, Day 85 pre-dose, Day 183 pre-dose, and 3 and 6 months after study treatment discontinuation (up to 39 months))
- Change From Baseline in Physical Functioning Score of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients 30 (EORTC QLQ-C30)(At baseline, every 3 wks until Wk 18, and every 4 wks until the second progression. Assessed until 12 Apr 2023 DCO, up to 35 months. The average treatment effect over the first 12 months after randomisation is presented.)
- Change From Baseline in Global Health Status/QoL Score of the EORTC QLQ-C30(At baseline, every 3 wks until Wk 18, and every 4 wks until the second progression. Assessed until 12 Apr 2023 DCO, up to 35 months. The average treatment effect over the first 12 months after randomisation is presented.)