A Study of Neoadjuvant/Adjuvant Durvalumab for the Treatment of Patients With Resectable Non-small Cell Lung Cancer

Non-Small Cell Lung Cancer Clinical Trial

— AEGEAN  

Official title:

A Phase III, Double-blind, Placebo-controlled, Multi-center International Study of Neoadjuvant/Adjuvant Durvalumab for the Treatment of Patients With Resectable Stages II and III Non-small Cell Lung Cancer (AEGEAN)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03800134
• Other study ID #: D9106C00001
• Secondary ID: 2018-002997-29
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 6, 2018
• Est. completion date: September 11, 2028

Study information

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

Clinical Trial Summary

This is a Phase III, randomized, double-blind, placebo-controlled, multi-center international study assessing the activity of durvalumab and chemotherapy administered prior to surgery compared with placebo and chemotherapy administered prior to surgery in terms of pathological complete response.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 826
• Est. completion date: September 11, 2028
• Est. primary completion date: November 10, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

Inclusion Criteria:

• Age =18 years
• Newly diagnosed and previously untreated patients with histologically or cytologically documented NSCLC with resectable (Stage IIA to select [ie, N2] Stage IIIB) disease
• World Health Organization (WHO)/ECOG PS of 0 or 1 at enrollment
• At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 Target Lesion (TL) at baseline
• No prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies, excluding therapeutic anticancer vaccines
• Adequate organ and marrow function
• Confirmation of a patient's tumour PD-L1 status
• Provision of sufficient tumour biopsy sample for evaluation and confirmation of EGFR and ALK status
• Planned surgery must comprise lobectomy, sleeve resection, or bilobectomy

Exclusion Criteria:

• History of allogeneic organ transplantation
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome)
• History of another primary malignancy
• History of active primary immunodeficiency
• Active infection including tuberculosis hepatitis B and C, or human immunodeficiency virus
• Deemed unresectable NSCLC by multidisciplinary evaluation
• Patients who have pre-operative radiotherapy treatment as part of their care plan
• Patients who have brain metastases or spinal cord compression
• Stage IIIB N3 and Stages IIIC, IVA, and IVB NSCLC
• Known allergy or hypersensitivity to any of the study drugs or excipients
• Existence of more than one primary tumour such as mixed small cell and NSCLC histology
• Patients whose planned surgery at enrollment includes any of the following procedures:

pneumonectomy, segmentectomies, or wedge resections

• Patients with a documented test result confirming the presence of EGFRm or ALK translocation

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Durvalumab
1500mg on Day 1 of each 3-week cycle for 4 cycles during the neoadjuvant period and 1500mg on Day 1 of each 4-week cycle for 12 cycles during the adjuvant period

Other:
• Placebo
Day 1 of each 3-week cycle for 4 cycles during the neoadjuvant period and Day 1 of each 4-week cycle for 12 cycles during the adjuvant period

Drug:
• Carboplatin
Area under the curve of 5/6 on Day 1 of each 3-week cycle for 4 cycles
• Cisplatin
75 mg/m2 on Day 1 of each 3-week cycle, for 4 cycles
• Pemetrexed
500 mg/m2 on Day 1 of each 3-week cycle for 4 cycles.
• Paclitaxel
200mg/m2 on Day 1 of each 3-week cycle for 4 cycles.
• Gemcitabine
1250 mg/m2 on Day 1 and Day 8 of each 3-week cycle, for 4 cycles.

Procedure:
• Surgery
Expected within 40 days from the last dose of IP following the completion of neoadjuvant treatment (4 cycles of platinum based chemotherapy concurrent with durvalumab or placebo)

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	La Plata
Argentina	Research Site	Pergamino
Argentina	Research Site	Rosario
Argentina	Research Site	San Salvador de Jujuy
Argentina	Research Site	Viedma
Austria	Research Site	Graz
Austria	Research Site	Innsbruck
Austria	Research Site	Rankweil
Austria	Research Site	Wien
Austria	Research Site	Wien
Belgium	Research Site	Gent
Belgium	Research Site	Liège
Belgium	Research Site	Mons
Brazil	Research Site	Barretos
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Campinas
Brazil	Research Site	Curitiba
Brazil	Research Site	Florianópolis
Brazil	Research Site	Natal
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Santa Maria
Brazil	Research Site	São José do Rio Preto
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	Teresina
Brazil	Research Site	Vitoria
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Kitchener	Ontario
Canada	Research Site	Levis	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Saskatoon	Saskatchewan
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Temuco
Chile	Research Site	Viña del Mar
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Changzhou
China	Research Site	Chengdu
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guiyang
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Hefei
China	Research Site	Kunming
China	Research Site	Linhai
China	Research Site	Nanchang
China	Research Site	Ningbo
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Shenyang
China	Research Site	Shenzhen
China	Research Site	Shenzhen
China	Research Site	Tianjin
China	Research Site	Urumqi
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Xiamen
China	Research Site	Xintai
China	Research Site	Yangzhou
China	Research Site	Zhengzhou
Costa Rica	Research Site	San José
Costa Rica	Research Site	San José
France	Research Site	Avignon Cedex
France	Research Site	Lyon Cedex 08
France	Research Site	Nice
France	Research Site	Toulon Cedex 9
France	Research Site	Vantoux
Germany	Research Site	Bielefeld
Germany	Research Site	Frankfurt am Main
Germany	Research Site	Immenstadt
Germany	Research Site	Köln
Hungary	Research Site	Budapest
Hungary	Research Site	Gyöngyös - Mátraháza
Hungary	Research Site	Gyor
Hungary	Research Site	Székesfehérvár
Hungary	Research Site	Törökbálint
India	Research Site	Ahmedabad
India	Research Site	Gurgaon
India	Research Site	Gurgaon
India	Research Site	Kolkata
India	Research Site	Manipal
India	Research Site	Mumbai
India	Research Site	Mumbai
India	Research Site	Mysuru
India	Research Site	Namakkal
India	Research Site	Nashik
India	Research Site	New Delhi
India	Research Site	New Delhi
India	Research Site	Thane
India	Research Site	Vishakhapatnam
Italy	Research Site	Ancona
Italy	Research Site	Bari
Italy	Research Site	Bergamo
Italy	Research Site	Firenze
Italy	Research Site	Milano
Italy	Research Site	Monza
Italy	Research Site	Padova
Italy	Research Site	Roma
Italy	Research Site	Verona
Japan	Research Site	Habikino-shi
Japan	Research Site	Himeji-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Iwakuni-shi
Japan	Research Site	Kitaadachi-gun
Japan	Research Site	Kitakyushu-shi
Japan	Research Site	Kurashiki shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Okayama-shi
Japan	Research Site	Osakasayama-shi
Japan	Research Site	Toyoake-shi
Japan	Research Site	Wakayama-shi
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon
Korea, Republic of	Research Site	Suwon-si
Mexico	Research Site	Aguascalientes
Mexico	Research Site	Chihuahua
Mexico	Research Site	Guadalajara
Mexico	Research Site	México
Mexico	Research Site	México
Mexico	Research Site	Monterrey
Mexico	Research Site	Monterrey
Mexico	Research Site	Pachuca de Soto
Netherlands	Research Site	Arnhem
Netherlands	Research Site	Nijmegen
Peru	Research Site	Bellavista
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Philippines	Research Site	Davao City
Philippines	Research Site	Iloilo City
Philippines	Research Site	Makati
Philippines	Research Site	Quezon City
Poland	Research Site	Bialystok
Poland	Research Site	Olsztyn
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Romania	Research Site	Suceava
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Krasnoyarsk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Nizhniy Novgorod
Russian Federation	Research Site	Obninsk
Russian Federation	Research Site	Rostov-on-Don
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	Tomsk
Russian Federation	Research Site	Yaroslavl
Spain	Research Site	Alicante
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Spain	Research Site	Oviedo
Spain	Research Site	Pamplona
Spain	Research Site	San Sebastian
Spain	Research Site	Santiago De Compostela (A Coruña)
Taiwan	Research Site	Changhua
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung City
Taiwan	Research Site	Tainan City
Taiwan	Research Site	Tainan City
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Chiang Mai
Thailand	Research Site	Chiang Rai
Thailand	Research Site	Khon Kaen
Thailand	Research Site	Lampang
United States	Research Site	Ashland	Kentucky
United States	Research Site	Aurora	Colorado
United States	Research Site	Austin	Texas
United States	Research Site	Bend	Oregon
United States	Research Site	Boca Raton	Florida
United States	Research Site	Charleston	South Carolina
United States	Research Site	Charleston	South Carolina
United States	Research Site	Chicago	Illinois
United States	Research Site	Duarte	California
United States	Research Site	Duluth	Minnesota
United States	Research Site	Durham	North Carolina
United States	Research Site	Fairfax	Virginia
United States	Research Site	Fort Worth	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Jacksonville	Florida
United States	Research Site	Kirkland	Washington
United States	Research Site	Lexington	Kentucky
United States	Research Site	Medford	Oregon
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Morristown	New Jersey
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Orange	California
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Seattle	Washington
United States	Research Site	Shirley	New York
United States	Research Site	Silver Spring	Maryland
United States	Research Site	Towson	Maryland
United States	Research Site	Wichita	Kansas
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  China,  Costa Rica,  France,  Germany,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Peru,  Philippines,  Poland,  Romania,  Russian Federation,  Spain,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of participants with adverse events as assessed by CTCAE v5.0		From date of randomization to 3 months after last dose of IP
Primary	Pathological Complete Response (pCR) in modified intent-to-treat (mITT) population	Defined as the lack of any viable tumour cells after complete evaluation in the resected lung cancer specimen and all sampled regional lymph nodes.	Up to approximately 15 weeks after randomization
Primary	Event-Free Survival (EFS) in modified intent to treat (mITT) population	An event is defined as documented RECIST 1.1 local or distant recurrence of lung cancer; death due to any cause; disease progression that precludes surgery or discovered upon attempting surgery that prevents completion of surgery.	Up to 5.5 years after first patient randomized.
Secondary	Disease-free survival (DFS) in modified resected population		From date of randomization to approximately 5.5 years after date of resection
Secondary	Major Pathological Response (mPR) in modified intent to treat (mITT) population		Up to approximately 15 weeks after randomization
Secondary	Overall Survival (OS) in modified intent to treat (mITT) population		From date of randomization to 5.5 years after randomization
Secondary	Event-free survival (EFS) in PD-L1-TC =1% patients in modified intent to treat (mITT) population		From date of randomization to 5.5 years after randomization
Secondary	pCR in PD-L1-TC =1% patients in modified intent to treat (mITT) population		Up to approximately 15 weeks after randomization
Secondary	Disease-Free Survival (DFS) in PD-L1-TC =1% patients in modified resected population		From date of randomization to 5.5 years after date of resection
Secondary	Major Pathological Response (mPR) in PD-L1-TC =1% patients in modified intent to treat (mITT) population		Up to approximately 15 weeks after randomization
Secondary	Overall Survival (OS) in PD-L1-TC =1% patients in modified intent to treat (mITT) population		From date of randomization to 5.5 years after randomization.
Secondary	To assess disease-related symptoms and HRQoL (EORTC QLQ-C30) in patients treated with durvalumab + chemotherapy prior to surgery followed by durvalumab post-surgery compared with placebo + chemotherapy prior to surgery followed by placebo post-surgery	To assess disease-related symptoms, functioning, and global health status/quality of life in patients.	From date of screening to 6 months after last dose of IP
Secondary	To assess disease-related symptoms and HRQoL (EORTC QLQ-LC13) in patients treated with durvalumab + chemotherapy prior to surgery followed by durvalumab post-surgery compared with placebo + chemotherapy prior to surgery followed by placebo post-surgery	To assess disease-related symptoms, functioning, and global health status/quality of life in patients.	From date of screening to 6 months after last dose of IP
Secondary	To assess the PK of durvalumab in blood	To assess concentration of durvalumab in bloodstream.	From date of randomization to 2 months after resection
Secondary	Presence of ADA for durvalumab	To evaluate the presence of antibodies following treatment with study medications.	From date of randomization to 3 months after last dose of IP