Clinical trial NCT04269200: Durvalumab With or Without Olaparib as Maintenance Therapy After First-Line Treatment of Advanced and Recurrent Endometrial Cancer
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Endometrial Neoplasms
Keywords: Cancer of Endometrium
Cancer of the Endometrium
Carcinoma of Endometrium
Endometrial Cancer
Endometrial Carcinoma
Endometrium Cancer
Neoplasms, Endometrial
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: The Gynecologic Oncology Group (GOG) Foundation Inc
name: The European Network for Gynaecological Oncological Trial groups (ENGOT)
First posted: 2020-02-13
Enrollment: 813
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 150
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double-blind, placebo-controlled
Primary purpose: TREATMENT

Brief 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.

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

Eligibility 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:

  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.

Primary outcomes:
measure: Progression Free Survival (PFS) for Arm B vs Arm A and Arm C vs Arm A
timeFrame: Up to 4 years
Secondary outcomes:
measure: Second Progression (PFS2)
timeFrame: Up to 6 years
measure: Overall Survival (OS)
timeFrame: Up to 6 years
measure: Objective Response Rate (ORR)
timeFrame: Up to 4 years
measure: Duration of response (DoR)
timeFrame: Up to 4 years
measure: Time to first subsequent therapy (TFST)
timeFrame: Up to 6 years
measure: Time to second subsequent therapy (TSST)
timeFrame: Up to 6 years
measure: Time to discontinuation or death (TDT)
timeFrame: Up to 6 years
measure: The pharmacokinetics (PK) of durvalumab will be determined after steady state doses
timeFrame: Up to 4 years
measure: Safety and tolerability of drugs by assessment of AEs/SAEs
timeFrame: Up to 6 years
measure: The immunogenicity of durvalumab as determined by concentration of Anti-drug antibodies (ADA) to durvalumab
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Concord
country: United States
facility: Research Site
state: California
city: La Jolla
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Santa Barbara
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Fort Lauderdale
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Savannah
country: United States
facility: Research Site
state: Georgia
city: Honolulu
country: United States
facility: Research Site
state: Hawaii
city: Arlington Heights
country: United States
facility: Research Site
state: Illinois
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Baton Rouge
country: United States
facility: Research Site
state: Louisiana
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Saint Paul
country: United States
facility: Research Site
state: Minnesota
city: Jackson
country: United States
facility: Research Site
state: Mississippi
city: Lebanon
country: United States
facility: Research Site
state: New Hampshire
city: Camden
country: United States
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state: New Jersey
city: Paramus
country: United States
facility: Research Site
state: New Jersey
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Pinehurst
country: United States
facility: Research Site
state: North Carolina
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Dayton
country: United States
facility: Research Site
state: Ohio
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Tulsa
country: United States
facility: Research Site
state: Oklahoma
city: Eugene
country: United States
facility: Research Site
state: Oregon
city: Tigard
country: United States
facility: Research Site
state: Oregon
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Providence
country: United States
facility: Research Site
state: Rhode Island
city: Sioux Falls
country: United States
facility: Research Site
state: South Dakota
city: Chattanooga
country: United States
facility: Research Site
state: Tennessee
city: Germantown
country: United States
facility: Research Site
state: Tennessee
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
city: Bedford
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Sugar Land
country: United States
facility: Research Site
state: Texas
city: Tyler
country: United States
facility: Research Site
state: Texas
city: Webster
country: United States
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state: Texas
city: Fairfax
country: United States
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state: Virginia
city: Norfolk
country: United States
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state: Virginia
city: Seattle
country: United States
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state: Washington
city: Morgantown
country: United States
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state: West Virginia
city: Madison
country: United States
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state: Wisconsin
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Clayton
country: Australia
facility: Research Site
city: Malvern
country: Australia
facility: Research Site
city: Melbourne
country: Australia
facility: Research Site
city: Nedlands
country: Australia
facility: Research Site
city: Sydney
country: Australia
facility: Research Site
city: Bruges
country: Belgium
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Charleroi
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Hasselt
country: Belgium
facility: Research Site
city: Kortrijk
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Libramont-Chevigny
country: Belgium
facility: Research Site
city: Liège
country: Belgium
facility: Research Site
city: Belo Horizonte
country: Brazil
facility: Research Site
city: Belo Horizonte
country: Brazil
facility: Research Site
city: Curitiba
country: Brazil
facility: Research Site
city: Passo Fundo
country: Brazil
facility: Research Site
city: Pelotas
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
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city: Porto Alegre
country: Brazil
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city: Rio de Janeiro
country: Brazil
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city: Sao Paulo
country: Brazil
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city: Sao Paulo
country: Brazil
facility: Research Site
city: São José do Rio Preto
country: Brazil
facility: Research Site
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Dalian
country: China
facility: Research Site
city: Dalian
country: China
facility: Research Site
city: Guangdong
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Haikou
country: China
facility: Research Site
city: Harbin
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Nanning
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Tianjin
country: China
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city: Wuhan
country: China
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city: Wuhan
country: China
facility: Research Site
city: Zhanjiang
country: China
facility: Research Site
city: Zhengzhou
country: China
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city: Zhengzhou
country: China
facility: Research Site
city: Barranquilla
country: Colombia
facility: Research Site
city: Bogota
country: Colombia
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city: Bogota
country: Colombia
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city: Bogota
country: Colombia
facility: Research Site
city: Cali
country: Colombia
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city: Medellin
country: Colombia
facility: Research Site
city: Medellín
country: Colombia
facility: Research Site
city: Monteria
country: Colombia
facility: Research Site
city: Pereira
country: Colombia
facility: Research Site
city: Tallinn
country: Estonia
facility: Research Site
city: Tartu
country: Estonia
facility: Research Site
city: Bonn
country: Germany
facility: Research Site
city: Chemnitz
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Chaidari
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: HKG
country: Hong Kong
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Győr
country: Hungary
facility: Research Site
city: Szolnok
country: Hungary
facility: Research Site
city: Hisar
country: India
facility: Research Site
city: Mumbai
country: India
facility: Research Site
city: Be'er Ya'akov
country: Israel
facility: Research Site
city: Hadera
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Nahariya
country: Israel
facility: Research Site
city: Tel Aviv
country: Israel
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Kashiwa-shi
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Kurume-shi
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
facility: Research Site
city: Matsuyama-shi
country: Japan
facility: Research Site
city: Minato-ku
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Nakagami-gun
country: Japan
facility: Research Site
city: Niigata-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Osaka
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Toon-Shi
country: Japan
facility: Research Site
city: Tsu-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon
country: Korea, Republic of
facility: Research Site
city: Yangsan-si
country: Korea, Republic of
facility: Research Site
city: Kaunas
country: Lithuania
facility: Research Site
city: Vilnius
country: Lithuania
facility: Research Site
city: Vilnius
country: Lithuania
facility: Research Site
city: Aguascalientes
country: Mexico
facility: Research Site
city: Mexico
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: Oaxaca
country: Mexico
facility: Research Site
city: Queretaro
country: Mexico
facility: Research Site
city: San Luis Potosi
country: Mexico
facility: Research Site
city: Veracruz
country: Mexico
facility: Research Site
city: Gdansk
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Anzorey
country: Russian Federation
facility: Research Site
city: Kazan, Tatarstan
country: Russian Federation
facility: Research Site
city: Krasnodar
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saransk
country: Russian Federation
facility: Research Site
city: Sochi
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: El Palmar
country: Spain
facility: Research Site
city: Girona
country: Spain
facility: Research Site
city: Jaén
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Mallorca
country: Spain
facility: Research Site
Study officials:
affiliation: The University of Texas MD Anderson Cancer Center
name: Shannon N. Westin, MD, MPH, FACOG
role: PRINCIPAL_INVESTIGATOR
References: