Durvalumab With or Without Olaparib as Maintenance Therapy After First-Line Treatment of Advanced and Recurrent Endometrial Cancer
Summary
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.
Key Facts
Lead Sponsor
AstraZeneca
Enrollment
805
Start Date
2020-05-05
Completion Date
2024-07-08
Study Type
INTERVENTIONAL
Official Title
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)
Interventions
Conditions
Eligibility
Age Range
18 Years – 150 Years
Sex
FEMALE
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: 1. Newly diagnosed Stage III disease (measurable disease per RECIST 1.1 following surgery or diagnostic biopsy), 2. Newly diagnosed Stage IV disease (with or without disease following surgery or diagnostic biopsy) 3. 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. Exclusion Criteria: * 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.
Outcome Measures
Primary Outcomes
Progression-free Survival (PFS) According to RECIST 1.1, Based on Investigator Assessments
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
Time frame: 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
Secondary Outcomes
Overall Survival (OS) Analysis
To determine 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 in newly diagnosed advanced or recurrent endometrial cancer patients by assessment of OS
Time frame: 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
To determine 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 in newly diagnosed advanced or recurrent endometrial cancer patients by assessment of PFS2
Time frame: 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
To determine 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 in newly diagnosed advanced or recurrent endometrial cancer patients by assessment of ORR
Time frame: 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
To determine 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 in newly diagnosed advanced or recurrent endometrial cancer patients by assessment of DoR
Time frame: 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)
To determine 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 in newly diagnosed advanced or recurrent endometrial cancer patients by assessment of TFST
Time frame: 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)
To determine 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 in newly diagnosed advanced or recurrent endometrial cancer patients by assessment of TSST
Time frame: 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)
To determine 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 in newly diagnosed advanced or recurrent endometrial cancer patients by assessment of TDT
Time frame: Time elapsed from randomisation to study treatment discontinuation or death. Assessed through study completion, up to 83 months
Serum Concentration of Durvalumab
To characterise the pharmacokinetics (PK) of durvalumab and durvalumab in combination with olaparib
Time frame: 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
To characterise the immunogenicity of durvalumab and durvalumab in combination with olaparib
Time frame: 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)
To determine effects on symptoms, functioning, and overall health related quality of life (HRQoL) 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 alone in newly diagnosed advanced or recurrent endometrial cancer patients. The physical functioning score is a score from 0 to 100. Higher scores on the physical functioning score indicate better health status/function.
Time frame: 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
To determine effects on symptoms, functioning, and overall HRQoL 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 alone in newly diagnosed advanced or recurrent endometrial cancer patients. The global health status/quality of life (QoL) is a score from 0 to 100. Higher scores on the global health status/QoL indicate better health status/function.
Time frame: 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.
Locations
Research Site, Tucson, United States
Research Site, Concord, United States
Research Site, La Jolla, United States
Research Site, San Francisco, United States
Research Site, Santa Barbara, United States
Research Site, Aurora, United States
Research Site, Fort Lauderdale, United States
Research Site, Tampa, United States
Research Site, Savannah, United States
Research Site, Honolulu, United States
Research Site, Arlington Heights, United States
Research Site, Chicago, United States
Research Site, Indianapolis, United States
Research Site, Louisville, United States
Research Site, Baton Rouge, United States
Research Site, Boston, United States
Research Site, Saint Paul, United States
Research Site, Jackson, United States
Research Site, Lebanon, United States
Research Site, Camden, United States
Research Site, Paramus, United States
Research Site, New York, United States
Research Site, New York, United States
Research Site, Pinehurst, United States
Research Site, Cleveland, United States
Research Site, Cleveland, United States
Research Site, Dayton, United States
Research Site, Oklahoma City, United States
Research Site, Tulsa, United States
Research Site, Eugene, United States
Research Site, Tigard, United States
Research Site, Pittsburgh, United States
Research Site, Providence, United States
Research Site, Sioux Falls, United States
Research Site, Chattanooga, United States
Research Site, Germantown, United States
Research Site, Knoxville, United States
Research Site, Bedford, United States
Research Site, Dallas, United States
Research Site, Houston, United States
Research Site, San Antonio, United States
Research Site, Sugar Land, United States
Research Site, Tyler, United States
Research Site, Webster, United States
Research Site, Fairfax, United States
Research Site, Norfolk, United States
Research Site, Seattle, United States
Research Site, Morgantown, United States
Research Site, Madison, United States
Research Site, Milwaukee, United States
Research Site, Clayton, Australia
Research Site, Malvern, Australia
Research Site, Melbourne, Australia
Research Site, Nedlands, Australia
Research Site, Sydney, Australia
Research Site, Bruges, Belgium
Research Site, Brussels, Belgium
Research Site, Charleroi, Belgium
Research Site, Ghent, Belgium
Research Site, Hasselt, Belgium
Research Site, Kortrijk, Belgium
Research Site, Leuven, Belgium
Research Site, Libramont-Chevigny, Belgium
Research Site, Liège, Belgium
Research Site, Belo Horizonte, Brazil
Research Site, Belo Horizonte, Brazil
Research Site, Curitiba, Brazil
Research Site, Passo Fundo, Brazil
Research Site, Pelotas, Brazil
Research Site, Porto Alegre, Brazil
Research Site, Porto Alegre, Brazil
Research Site, Porto Alegre, Brazil
Research Site, Rio de Janeiro, Brazil
Research Site, São José do Rio Preto, Brazil
Research Site, São Paulo, Brazil
Research Site, São Paulo, Brazil
Research Site, Calgary, Canada
Research Site, Toronto, Canada
Research Site, Toronto, Canada
Research Site, Montreal, Canada
Research Site, Montreal, Canada
Research Site, Montreal, Canada
Research Site, Montreal, Canada
Research Site, Beijing, China
Research Site, Beijing, China
Research Site, Changchun, China
Research Site, Changchun, China
Research Site, Changsha, China
Research Site, Changsha, China
Research Site, Chengdu, China
Research Site, Chongqing, China
Research Site, Chongqing, China
Research Site, Dalian, China
Research Site, Dalian, China
Research Site, Guangdong, China
Research Site, Guangzhou, China
Research Site, Haikou, China
Research Site, Harbin, China
Research Site, Hefei, China
Research Site, Nanning, China
Research Site, Shanghai, China
Research Site, Shenyang, China
Research Site, Taiyuan, China
Research Site, Tianjin, China
Research Site, Wuhan, China
Research Site, Wuhan, China
Research Site, Zhanjiang, China
Research Site, Zhengzhou, China
Research Site, Zhengzhou, China
Research Site, Barranquilla, Colombia
Research Site, Bogotá, Colombia
Research Site, Bogotá, Colombia
Research Site, Bogotá, Colombia
Research Site, Cali, Colombia
Research Site, Medellín, Colombia
Research Site, Medellín, Colombia
Research Site, Montería, Colombia
Research Site, Pereira, Colombia
Research Site, Tallinn, Estonia
Research Site, Tartu, Estonia
Research Site, Bonn, Germany
Research Site, Chemnitz, Germany
Research Site, Dresden, Germany
Research Site, Erlangen, Germany
Research Site, Leipzig, Germany
Research Site, Athens, Greece
Research Site, Chaïdári, Greece
Research Site, Thessaloniki, Greece
Research Site, Hong Kong, Hong Kong
Research Site, Budapest, Hungary
Research Site, Budapest, Hungary
Research Site, Budapest, Hungary
Research Site, Debrecen, Hungary
Research Site, Győr, Hungary
Research Site, Szolnok, Hungary
Research Site, Hisar, India
Research Site, Mumbai, India
Research Site, Be’er Ya‘aqov, Israel
Research Site, Hadera, Israel
Research Site, Jerusalem, Israel
Research Site, Nahariya, Israel
Research Site, Tel Aviv, Israel
Research Site, Chūōku, Japan
Research Site, Kashiwa-shi, Japan
Research Site, Kōtoku, Japan
Research Site, Kurume-shi, Japan
Research Site, Kyoto, Japan
Research Site, Matsuyama, Japan
Research Site, Minatoku, Japan
Research Site, Nagoya, Japan
Research Site, Nakagami-gun, Japan
Research Site, Niigata, Japan
Research Site, Osaka, Japan
Research Site, Osaka, Japan
Research Site, Sapporo, Japan
Research Site, Shinjuku-ku, Japan
Research Site, Sunto-gun, Japan
Research Site, Toon-Shi, Japan
Research Site, Tsu, Japan
Research Site, Yokohama, Japan
Research Site, Kaunas, Lithuania
Research Site, Vilnius, Lithuania
Research Site, Vilnius, Lithuania
Research Site, Aguascalientes, Mexico
Research Site, México, Mexico
Research Site, Monterrey, Mexico
Research Site, Oaxaca City, Mexico
Research Site, Querétaro, Mexico
Research Site, San Luis Potosí City, Mexico
Research Site, Veracruz, Mexico
Research Site, Gdansk, Poland
Research Site, Lodz, Poland
Research Site, Lublin, Poland
Research Site, Olsztyn, Poland
Research Site, Olsztyn, Poland
Research Site, Anzorey, Russia
Research Site, Kazan, Tatarstan, Russia
Research Site, Krasnodar, Russia
Research Site, Moscow, Russia
Research Site, Moscow, Russia
Research Site, Saint Petersburg, Russia
Research Site, Saransk, Russia
Research Site, Sochi, Russia
Research Site, Singapore, Singapore
Research Site, Singapore, Singapore
Research Site, Singapore, Singapore
Research Site, Goyang-si, South Korea
Research Site, Seoul, South Korea
Research Site, Seoul, South Korea
Research Site, Seoul, South Korea
Research Site, Seoul, South Korea
Research Site, Seoul, South Korea
Research Site, Seoul, South Korea
Research Site, Suwon, South Korea
Research Site, Yangsan, South Korea
Research Site, Barcelona, Spain
Research Site, Barcelona, Spain
Research Site, El Palmar, Spain
Research Site, Girona, Spain
Research Site, Jaén, Spain
Research Site, Madrid, Spain
Research Site, Mallorca, Spain