Durvalumab With or Without Olaparib as Maintenance Therapy After First-Line Treatment of Advanced and Recurrent Endometrial Cancer (DUO-E)

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Endometrial Neoplasms
• Intervention / Treatment: Drug: durvalumab placebo; Drug: olaparib placebo; Drug: Carboplatin; Drug: Paclitaxel; Biological: durvalumab; Drug: olaparib

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 805
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Clayton, Australia, 3168
    • Research Site
  • Malvern, Australia, 3144
    • Research Site
  • Melbourne, Australia, 3000
    • Research Site
  • Nedlands, Australia, 6009
    • Research Site
  • Sydney, Australia, NSW 2145
    • Research Site
• Belgium
  • Bruges, Belgium, 8000
    • Research Site
  • Bruxelles, Belgium, 1200
    • Research Site
  • Charleroi, Belgium, 6000
    • Research Site
  • Gent, Belgium, 9000
    • Research Site
  • Hasselt, Belgium, 3500
    • Research Site
  • Kortrijk, Belgium, 8500
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Libramont-Chevigny, Belgium, 6800
    • Research Site
  • Liège, Belgium, 4000
    • Research Site
• Brazil
  • Belo Horizonte, Brazil, 30130-090
    • Research Site
  • Belo Horizonte, Brazil, 30150-274
    • Research Site
  • Curitiba, Brazil, 80520-174
    • Research Site
  • Passo Fundo, Brazil, 99010-080
    • Research Site
  • Pelotas, Brazil, 96020-080
    • Research Site
  • Porto Alegre, Brazil, 90035-003
    • Research Site
  • Porto Alegre, Brazil, 90020-090
    • Research Site
  • Porto Alegre, Brazil, 90110-270
    • Research Site
  • Rio de Janeiro, Brazil, 20231-050
    • Research Site
  • Sao Paulo, Brazil, 01246-000
    • Research Site
  • Sao Paulo, Brazil, 01317-001
    • Research Site
  • São José do Rio Preto, Brazil, 15090-000
    • Research Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Research Site
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Research Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Research Site
    • Montreal, Quebec, Canada, H1T 2M4
      • Research Site
    • Montreal, Quebec, Canada, H2L 4M1
      • Research Site
    • Montreal, Quebec, Canada, H3A 1A1
      • Research Site
• China
  • Beijing, China, 100142
    • Research Site
  • Beijing, China, 100034
    • Research Site
  • Changchun, China, 130012
    • Research Site
  • Changchun, China, 130021
    • Research Site
  • Changsha, China, 410008
    • Research Site
  • Changsha, China, 410003
    • Research Site
  • Chengdu, China, 610041
    • Research Site
  • Chongqing, China
    • Research Site
  • Chongqing, China, 400038
    • Research Site
  • Dalian, China, 116027
    • Research Site
  • Dalian, China, 116001
    • Research Site
  • Guangdong, China
    • Research Site
  • Guangzhou, China, 510060
    • Research Site
  • Haikou, China, 570311
    • Research Site
  • Harbin, China, 150081
    • Research Site
  • Hefei, China, 230031
    • Research Site
  • Nanning, China, 530021
    • Research Site
  • Shanghai, China, 200032
    • Research Site
  • Shenyang, China, 110042
    • Research Site
  • Taiyuan, China, 030001
    • Research Site
  • Tianjin, China, 300060
    • Research Site
  • Wuhan, China, 430022
    • Research Site
  • Wuhan, China, 430030
    • Research Site
  • Zhanjiang, China, 524001
    • Research Site
  • Zhengzhou, China, 450008
    • Research Site
  • Zhengzhou, China
    • Research Site
• Colombia
  • Barranquilla, Colombia, 80020
    • Research Site
  • Bogota, Colombia, 111511
    • Research Site
  • Bogota, Colombia, 110321
    • Research Site
  • Bogota, Colombia, 111321
    • Research Site
  • Cali, Colombia, 760043
    • Research Site
  • Medellin, Colombia, 50030
    • Research Site
  • Medellín, Colombia, 50025
    • Research Site
  • Monteria, Colombia, 23001
    • Research Site
  • Pereira, Colombia, 660001
    • Research Site
• Estonia
  • Tallinn, Estonia, 1131
    • Research Site
  • Tartu, Estonia, 50406
    • Research Site
• Germany
  • Bonn, Germany, 53127
    • Research Site
  • Chemnitz, Germany, 09116
    • Research Site
  • Dresden, Germany, 01307
    • Research Site
  • Leipzig, Germany, 4103
    • Research Site
• Greece
  • Athens, Greece, 11528
    • Research Site
  • Chaidari, Greece, 124 62
    • Research Site
  • Thessaloniki, Greece, 54645
    • Research Site
• Hong Kong
  • HKG, Hong Kong
    • Research Site
  • Hong Kong, Hong Kong
    • Research Site
• Hungary
  • Budapest, Hungary, 1145
    • Research Site
  • Budapest, Hungary, 1122
    • Research Site
  • Budapest, Hungary, 1062
    • Research Site
  • Debrecen, Hungary, 4032
    • Research Site
  • Győr, Hungary, 9024
    • Research Site
  • Szolnok, Hungary, 5004
    • Research Site
• India
  • Hisar, India, 125005
    • Research Site
  • Mumbai, India, 400012
    • Research Site
• Israel
  • Be'er Ya'akov, Israel, 70300
    • Research Site
  • Hadera, Israel, 3810101
    • Research Site
  • Jerusalem, Israel, 91031
    • Research Site
  • Nahariya, Israel, 22100
    • Research Site
  • Tel Aviv, Israel, 6423906
    • Research Site
• Japan
  • Chuo-ku, Japan, 104-0045
    • Research Site
  • Kashiwa-shi, Japan, 277-8567
    • Research Site
  • Koto-ku, Japan, 135-8550
    • Research Site
  • Kurume-shi, Japan, 830-0011
    • Research Site
  • Kyoto-shi, Japan, 606-8507
    • Research Site
  • Matsuyama-shi, Japan, 791-0280
    • Research Site
  • Minato-ku, Japan, 105-8471
    • Research Site
  • Nagoya-shi, Japan, 464-8681
    • Research Site
  • Nakagami-gun, Japan, 903-0215
    • Research Site
  • Niigata-shi, Japan, 951-8520
    • Research Site
  • Osaka, Japan, 637086
    • Research Site
  • Osaka-shi, Japan, 541-8567
    • Research Site
  • Sapporo-shi, Japan, 003-0804
    • Research Site
  • Shinjuku-ku, Japan, 160-8582
    • Research Site
  • Sunto-gun, Japan, 411-8777
    • Research Site
  • Toon-Shi, Japan, 791-0295
    • Research Site
  • Tsu-shi, Japan, 514-8507
    • Research Site
  • Yokohama-shi, Japan, 236-0004
    • Research Site
• Korea, Republic of
  • Goyang-si, Korea, Republic of, 10408
    • Research Site
  • Seoul, Korea, Republic of, 03722
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Research Site
  • Seoul, Korea, Republic of, 06351
    • Research Site
  • Seoul, Korea, Republic of, 06591
    • Research Site
  • Seoul, Korea, Republic of, 138-736
    • Research Site
  • Seoul, Korea, Republic of, 01812
    • Research Site
  • Suwon, Korea, Republic of, 443380
    • Research Site
  • Yangsan-si, Korea, Republic of, 50612
    • Research Site
• Lithuania
  • Kaunas, Lithuania, 50161
    • Research Site
  • Vilnius, Lithuania, 08661
    • Research Site
  • Vilnius, Lithuania, 8660
    • Research Site
• Mexico
  • Aguascalientes, Mexico, 20116
    • Research Site
  • Mexico, Mexico, 06700
    • Research Site
  • Monterrey, Mexico, 64000
    • Research Site
  • Oaxaca, Mexico, 68000
    • Research Site
  • Queretaro, Mexico, 76090
    • Research Site
  • San Luis Potosi, Mexico, 78200
    • Research Site
  • Veracruz, Mexico, 91910
    • Research Site
• Poland
  • Gdansk, Poland, 80-214
    • Research Site
  • Lublin, Poland, 20-081
    • Research Site
  • Olsztyn, Poland, 10-228
    • Research Site
  • Olsztyn, Poland, 10-560
    • Research Site
  • Łódź, Poland, 93-513
    • Research Site
• Russian Federation
  • Anzorey, Russian Federation, 361350
    • Research Site
  • Kazan, Tatarstan, Russian Federation, 420029
    • Research Site
  • Krasnodar, Russian Federation, 350040
    • Research Site
  • Moscow, Russian Federation, 115478
    • Research Site
  • Moscow, Russian Federation, 117997
    • Research Site
  • Saransk, Russian Federation, 430032
    • Research Site
  • Sochi, Russian Federation, 354000
    • Research Site
  • St. Petersburg, Russian Federation, 198255
    • Research Site
• Singapore
  • Singapore, Singapore, 169610
    • Research Site
  • Singapore, Singapore, 119228
    • Research Site
  • Singapore, Singapore, 258499
    • Research Site
• Spain
  • Barcelona, Spain, 08907
    • Research Site
  • Barcelona, Spain, 08208
    • Research Site
  • El Palmar, Spain, 30120
    • Research Site
  • Girona, Spain, 17007
    • Research Site
  • Jaén, Spain, 23007
    • Research Site
  • Madrid, Spain, 28046
    • Research Site
  • Mallorca, Spain, 07120
    • Research Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Research Site
  • California
    • Concord, California, United States, 94520-2278
      • Research Site
    • La Jolla, California, United States, 92093
      • Research Site
    • San Francisco, California, United States, 94158
      • Research Site
    • Santa Barbara, California, United States, 93105
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Research Site
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Research Site
    • Tampa, Florida, United States, 33612
      • Research Site
  • Georgia
    • Savannah, Georgia, United States, 31404
      • Research Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96826
      • Research Site
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Research Site
    • Chicago, Illinois, United States, 60637
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Research Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70817
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Research Site
  • Minnesota
    • Saint Paul, Minnesota, United States, 55125
      • Research Site
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Research Site
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Research Site
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Research Site
    • Paramus, New Jersey, United States, 07652
      • Research Site
  • New York
    • New York, New York, United States, 10029
      • Research Site
    • New York, New York, United States, 10011
      • Research Site
  • North Carolina
    • Pinehurst, North Carolina, United States, 28374
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • Research Site
    • Cleveland, Ohio, United States, 44124
      • Research Site
    • Dayton, Ohio, United States, 45459
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Research Site
    • Tulsa, Oklahoma, United States, 74134
      • Research Site
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Research Site
    • Tigard, Oregon, United States, 97223
      • Research Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Research Site
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Research Site
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Research Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Research Site
    • Germantown, Tennessee, United States, 38138
      • Research Site
    • Knoxville, Tennessee, United States, 37920
      • Research Site
  • Texas
    • Bedford, Texas, United States, 76022
      • Research Site
    • Dallas, Texas, United States, 75231
      • Research Site
    • Houston, Texas, United States, 77030
      • Research Site
    • San Antonio, Texas, United States, 78240
      • Research Site
    • Sugar Land, Texas, United States, 77479
      • Research Site
    • Tyler, Texas, United States, 75702
      • Research Site
    • Webster, Texas, United States, 77598
      • Research Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Research Site
    • Norfolk, Virginia, United States, 23502
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98195
      • Research Site
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • Research Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Research Site
    • Milwaukee, Wisconsin, United States, 53226
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 148 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A (control); Platinum-based chemotherapy and durvalumab placebo followed by maintenance durvalumab placebo and olaparib placebo (tablets).	Drug: durvalumab placebo; Matching placebo for intravenous infusion; Drug: olaparib placebo; Placebo tablets to match olaparib; Drug: Carboplatin; Standard of care chemotherapy; Drug: Paclitaxel; Standard of care chemotherapy
Experimental: Arm B (durvalumab+placebo); Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib placebo	Drug: olaparib placebo; Placebo tablets to match olaparib; Drug: Carboplatin; Standard of care chemotherapy; Drug: Paclitaxel; Standard of care chemotherapy; Biological: durvalumab; Durvalumab by intravenous infusion
Experimental: Arm C (durvalumab+olaparib); Platinum-based chemotherapy and durvalumab followed by maintenance durvalumab and olaparib.	Drug: Carboplatin; Standard of care chemotherapy; Drug: Paclitaxel; Standard of care chemotherapy; Biological: durvalumab; Durvalumab by intravenous infusion; Drug: olaparib; Olaparib tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) for Arm B vs Arm A and Arm C vs Arm A	Defined as the time from randomisation until the date of objective disease progression (per RECIST 1.1 as assessed by investigator) or death (by any cause in the absence of progression)	Up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Second Progression (PFS2)	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	Up to 6 years
Overall Survival (OS)	Defined as the time from randomisation to death due to any cause	Up to 6 years
Objective Response Rate (ORR)	Defined as 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.	Up to 4 years
Duration of response (DoR)	Defined as time from the date of first documented response until date of documented progression or death in the absence of disease progression	Up to 4 years
Time to first subsequent therapy (TFST)	Defined as the 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	Up to 6 years
Time to second subsequent therapy (TSST)	Defined as the 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.	Up to 6 years
Time to discontinuation or death (TDT)	Defined as the time from randomisation to the earlier of the date of study treatment discontinuation or death.	Up to 6 years
The pharmacokinetics (PK) of durvalumab will be determined after steady state doses	Determination of durvalumab concentration in serum	Up to 4 years
Safety and tolerability of drugs by assessment of AEs/SAEs	Graded according to the National Cancer Institute (NCI CTCAE)	Up to 6 years
The immunogenicity of durvalumab as determined by concentration of Anti-drug antibodies (ADA) to durvalumab	Determination concentration of Anti-drug antibodies (ADA) to durvalumab in serum	Up to 4 years

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: The Gynecologic Oncology Group (GOG) Foundation Inc; The European Network for Gynaecological Oncological Trial groups (ENGOT)
• Investigators: Principal Investigator: Shannon N. Westin, MD, MPH, FACOG, The University of Texas MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2020
• Primary Completion (Estimated): March 5, 2025
• Study Completion (Estimated): March 5, 2025

Study Registration Dates

• First Submitted: February 10, 2020
• First Submitted That Met QC Criteria: February 12, 2020
• First Posted (Actual): February 13, 2020

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Endometrial Carcinoma; Endometrium Cancer; Endometrial Cancer; Cancer of Endometrium; Cancer of the Endometrium; Carcinoma of Endometrium; Neoplasms, Endometrial
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Endometrial Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Poly(ADP-ribose) Polymerase Inhibitors; Carboplatin; Paclitaxel; Olaparib; Durvalumab; Antibodies, Monoclonal
• Other Study ID Numbers: D9311C00001 (Other Identifier: AZ DCode); 2019-004112-60 (EudraCT Number); GOG-3041 (Other Identifier: Gynecologic Oncology Group(GOG) Foundation Inc); ENGOT-EN10 (Other Identifier: The European Network for Gynaecological Oncological Trial groups)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No