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

Endometrial Neoplasms Clinical Trial

— DUO-E  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04269200
• Other study ID #: D9311C00001
• Secondary ID: GOG-3041ENGOT-EN
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 5, 2020
• Est. completion date: March 5, 2025

Study information

• Verified date: March 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 805
• Est. completion date: March 5, 2025
• Est. primary completion date: March 5, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 150 Years

Eligibility

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.

Related Conditions & MeSH terms

• Endometrial Neoplasms

Intervention

Drug:
• olaparib
Olaparib tablets

Biological:
• durvalumab
Durvalumab by intravenous infusion

Drug:
• durvalumab placebo
Matching placebo for intravenous infusion
• olaparib placebo
Placebo tablets to match olaparib
• Carboplatin
Standard of care chemotherapy
• Paclitaxel
Standard of care chemotherapy

Locations

Country	Name	City	State
Australia	Research Site	Clayton
Australia	Research Site	Malvern
Australia	Research Site	Melbourne
Australia	Research Site	Nedlands
Australia	Research Site	Sydney
Belgium	Research Site	Bruges
Belgium	Research Site	Bruxelles
Belgium	Research Site	Charleroi
Belgium	Research Site	Gent
Belgium	Research Site	Hasselt
Belgium	Research Site	Kortrijk
Belgium	Research Site	Leuven
Belgium	Research Site	Libramont-Chevigny
Belgium	Research Site	Liège
Brazil	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	Sao Paulo
Brazil	Research Site	Sao Paulo
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
China	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
Colombia	Research Site	Barranquilla
Colombia	Research Site	Bogota
Colombia	Research Site	Bogota
Colombia	Research Site	Bogota
Colombia	Research Site	Cali
Colombia	Research Site	Medellin
Colombia	Research Site	Medellín
Colombia	Research Site	Monteria
Colombia	Research Site	Pereira
Estonia	Research Site	Tallinn
Estonia	Research Site	Tartu
Germany	Research Site	Bonn
Germany	Research Site	Chemnitz
Germany	Research Site	Dresden
Germany	Research Site	Leipzig
Greece	Research Site	Athens
Greece	Research Site	Chaidari
Greece	Research Site	Thessaloniki
Hong Kong	Research Site	HKG
Hong Kong	Research Site	Hong Kong
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Gyor
Hungary	Research Site	Szolnok
India	Research Site	Hisar
India	Research Site	Mumbai
Israel	Research Site	Be'er Ya'akov
Israel	Research Site	Hadera
Israel	Research Site	Jerusalem
Israel	Research Site	Nahariya
Israel	Research Site	Tel Aviv
Japan	Research Site	Chuo-ku
Japan	Research Site	Kashiwa-shi
Japan	Research Site	Koto-ku
Japan	Research Site	Kurume-shi
Japan	Research Site	Kyoto-shi
Japan	Research Site	Matsuyama-shi
Japan	Research Site	Minato-ku
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nakagami-gun
Japan	Research Site	Niigata-shi
Japan	Research Site	Osaka
Japan	Research Site	Osaka-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Sunto-gun
Japan	Research Site	Toon-Shi
Japan	Research Site	Tsu-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon
Korea, Republic of	Research Site	Yangsan-si
Lithuania	Research Site	Kaunas
Lithuania	Research Site	Vilnius
Lithuania	Research Site	Vilnius
Mexico	Research Site	Aguascalientes
Mexico	Research Site	Mexico
Mexico	Research Site	Monterrey
Mexico	Research Site	Oaxaca
Mexico	Research Site	Queretaro
Mexico	Research Site	San Luis Potosi
Mexico	Research Site	Veracruz
Poland	Research Site	Gdansk
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Poland	Research Site	Olsztyn
Poland	Research Site	Olsztyn
Russian Federation	Research Site	Anzorey
Russian Federation	Research Site	Kazan, Tatarstan
Russian Federation	Research Site	Krasnodar
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saransk
Russian Federation	Research Site	Sochi
Russian Federation	Research Site	St. Petersburg
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Spain	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
United States	Research Site	Arlington Heights	Illinois
United States	Research Site	Aurora	Colorado
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Bedford	Texas
United States	Research Site	Boston	Massachusetts
United States	Research Site	Camden	New Jersey
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Chicago	Illinois
United States	Research Site	Cleveland	Ohio
United States	Research Site	Cleveland	Ohio
United States	Research Site	Concord	California
United States	Research Site	Dallas	Texas
United States	Research Site	Dayton	Ohio
United States	Research Site	Eugene	Oregon
United States	Research Site	Fairfax	Virginia
United States	Research Site	Fort Lauderdale	Florida
United States	Research Site	Germantown	Tennessee
United States	Research Site	Honolulu	Hawaii
United States	Research Site	Houston	Texas
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Jackson	Mississippi
United States	Research Site	Knoxville	Tennessee
United States	Research Site	La Jolla	California
United States	Research Site	Lebanon	New Hampshire
United States	Research Site	Louisville	Kentucky
United States	Research Site	Madison	Wisconsin
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Morgantown	West Virginia
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Norfolk	Virginia
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Paramus	New Jersey
United States	Research Site	Pinehurst	North Carolina
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Providence	Rhode Island
United States	Research Site	Saint Paul	Minnesota
United States	Research Site	San Antonio	Texas
United States	Research Site	San Francisco	California
United States	Research Site	Santa Barbara	California
United States	Research Site	Savannah	Georgia
United States	Research Site	Seattle	Washington
United States	Research Site	Sioux Falls	South Dakota
United States	Research Site	Sugar Land	Texas
United States	Research Site	Tampa	Florida
United States	Research Site	Tigard	Oregon
United States	Research Site	Tucson	Arizona
United States	Research Site	Tulsa	Oklahoma
United States	Research Site	Tyler	Texas
United States	Research Site	Webster	Texas

Sponsors (3)

Lead Sponsor	Collaborator
AstraZeneca	The European Network for Gynaecological Oncological Trial groups (ENGOT), The Gynecologic Oncology Group (GOG) Foundation Inc

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  China,  Colombia,  Estonia,  Germany,  Greece,  Hong Kong,  Hungary,  India,  Israel,  Japan,  Korea, Republic of,  Lithuania,  Mexico,  Poland,  Russian Federation,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Overall Survival (OS)	Defined as the time from randomisation to death due to any cause	Up to 6 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	The pharmacokinetics (PK) of durvalumab will be determined after steady state doses	Determination of durvalumab concentration in serum	Up to 4 years
Secondary	Safety and tolerability of drugs by assessment of AEs/SAEs	Graded according to the National Cancer Institute (NCI CTCAE)	Up to 6 years
Secondary	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