Clinical trial NCT03800134: A Study of Neoadjuvant/Adjuvant Durvalumab for the Treatment of Patients With Resectable Non-small Cell Lung Cancer
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Keywords: Resectable Non-small Cell Lung Cancer, NSCLC, Carcinoma, Non-small Cell Lung Cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2019-01-11
Enrollment: 825
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Pathological Complete Response (pCR) in modified intent-to-treat (mITT) population
timeFrame: Up to approximately 15 weeks after randomization
measure: Event-Free Survival (EFS) in modified intent to treat (mITT) population
timeFrame: Up to 5.5 years after first patient randomized.
Secondary outcomes:
measure: Disease-free survival (DFS) in modified resected population
timeFrame: From date of randomization to approximately 5.5 years after date of resection
measure: Major Pathological Response (mPR) in modified intent to treat (mITT) population
timeFrame: Up to approximately 15 weeks after randomization
measure: Overall Survival (OS) in modified intent to treat (mITT) population
timeFrame: From date of randomization to 5.5 years after randomization
measure: Event-free survival (EFS) in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population
timeFrame: From date of randomization to 5.5 years after randomization
measure: pCR in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population
timeFrame: Up to approximately 15 weeks after randomization
measure: Disease-Free Survival (DFS) in PD-L1-TC ≥1% patients in modified resected population
timeFrame: From date of randomization to 5.5 years after date of resection
measure: Major Pathological Response (mPR) in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population
timeFrame: Up to approximately 15 weeks after randomization
measure: Overall Survival (OS) in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population
timeFrame: From date of randomization to 5.5 years after randomization.
measure: 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
timeFrame: From date of screening to 6 months after last dose of IP
measure: 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
timeFrame: From date of screening to 6 months after last dose of IP
measure: To assess the PK of durvalumab in blood
timeFrame: From date of randomization to 2 months after resection
measure: Presence of ADA for durvalumab
timeFrame: From date of randomization to 3 months after last dose of IP
Other outcomes:
measure: Number of participants with adverse events as assessed by CTCAE v5.0
timeFrame: From date of randomization to 3 months after last dose of IP
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Duarte
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Boca Raton
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
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state: Florida
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Wichita
country: United States
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state: Kansas
city: Ashland
country: United States
facility: Research Site
state: Kentucky
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Silver Spring
country: United States
facility: Research Site
state: Maryland
city: Towson
country: United States
facility: Research Site
state: Maryland
city: Duluth
country: United States
facility: Research Site
state: Minnesota
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Morristown
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: Shirley
country: United States
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state: New York
city: Durham
country: United States
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state: North Carolina
city: Bend
country: United States
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state: Oregon
city: Medford
country: United States
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state: Oregon
city: Pittsburgh
country: United States
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state: Pennsylvania
city: Charleston
country: United States
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state: South Carolina
city: Charleston
country: United States
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state: South Carolina
city: Austin
country: United States
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state: Texas
city: Fort Worth
country: United States
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state: Texas
city: Houston
country: United States
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state: Texas
city: Houston
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city: Fairfax
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state: Virginia
city: Kirkland
country: United States
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state: Washington
city: Seattle
country: United States
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state: Washington
city: Buenos Aires
country: Argentina
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city: Caba
country: Argentina
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city: Caba
country: Argentina
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city: La Plata
country: Argentina
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city: Pergamino
country: Argentina
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city: Rosario
country: Argentina
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city: San Salvador de Jujuy
country: Argentina
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city: Viedma
country: Argentina
facility: Research Site
city: Graz
country: Austria
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city: Innsbruck
country: Austria
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city: Rankweil
country: Austria
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city: Wien
country: Austria
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city: Wien
country: Austria
facility: Research Site
city: Gent
country: Belgium
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city: Liège
country: Belgium
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city: Mons
country: Belgium
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city: Barretos
country: Brazil
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city: Belo Horizonte
country: Brazil
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city: Campinas
country: Brazil
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city: Curitiba
country: Brazil
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country: Brazil
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city: Natal
country: Brazil
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country: Brazil
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city: Santa Maria
country: Brazil
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city: Sao Paulo
country: Brazil
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city: São José do Rio Preto
country: Brazil
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city: São Paulo
country: Brazil
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city: Teresina
country: Brazil
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city: Vitoria
country: Brazil
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city: Plovdiv
country: Bulgaria
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city: Sofia
country: Bulgaria
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city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Edmonton
country: Canada
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state: Alberta
city: Kitchener
country: Canada
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state: Ontario
city: Levis
country: Canada
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state: Quebec
city: Montreal
country: Canada
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state: Quebec
city: Montreal
country: Canada
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state: Quebec
city: Saskatoon
country: Canada
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state: Saskatchewan
city: Quebec
country: Canada
facility: Research Site
city: Santiago
country: Chile
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city: Santiago
country: Chile
facility: Research Site
city: Temuco
country: Chile
facility: Research Site
city: Viña del Mar
country: Chile
facility: Research Site
city: Beijing
country: China
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city: Beijing
country: China
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city: Beijing
country: China
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city: Beijing
country: China
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city: Changsha
country: China
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city: Changsha
country: China
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city: Changzhou
country: China
facility: Research Site
city: Chengdu
country: China
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city: Guangzhou
country: China
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city: Guangzhou
country: China
facility: Research Site
city: Guiyang
country: China
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city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
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city: Hangzhou
country: China
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city: Hangzhou
country: China
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city: Hefei
country: China
facility: Research Site
city: Kunming
country: China
facility: Research Site
city: Linhai
country: China
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city: Nanchang
country: China
facility: Research Site
city: Ningbo
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
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city: Shenyang
country: China
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city: Shenyang
country: China
facility: Research Site
city: Shenzhen
country: China
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city: Shenzhen
country: China
facility: Research Site
city: Tianjin
country: China
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city: Urumqi
country: China
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city: Wuhan
country: China
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city: Wuhan
country: China
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city: Xiamen
country: China
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city: Xintai
country: China
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city: Yangzhou
country: China
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city: Zhengzhou
country: China
facility: Research Site
city: San José
country: Costa Rica
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city: San José
country: Costa Rica
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city: Avignon Cedex
country: France
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city: Lyon Cedex 08
country: France
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city: Nice
country: France
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city: Toulon Cedex 9
country: France
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city: Vantoux
country: France
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city: Bielefeld
country: Germany
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city: Frankfurt am Main
country: Germany
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city: Immenstadt
country: Germany
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city: Köln
country: Germany
facility: Research Site
city: Budapest
country: Hungary
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city: Gyöngyös - Mátraháza
country: Hungary
facility: Research Site
city: Győr
country: Hungary
facility: Research Site
city: Székesfehérvár
country: Hungary
facility: Research Site
city: Törökbálint
country: Hungary
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city: Ahmedabad
country: India
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city: Gurgaon
country: India
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city: Gurgaon
country: India
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country: India
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country: India
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country: India
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country: India
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city: Mysuru
country: India
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city: Namakkal
country: India
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city: Nashik
country: India
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city: New Delhi
country: India
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country: India
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country: India
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city: Vishakhapatnam
country: India
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city: Ancona
country: Italy
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city: Bari
country: Italy
facility: Research Site
city: Bergamo
country: Italy
facility: Research Site
city: Firenze
country: Italy
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city: Milano
country: Italy
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city: Monza
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Roma
country: Italy
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city: Verona
country: Italy
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city: Habikino-shi
country: Japan
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city: Himeji-shi
country: Japan
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city: Hiroshima-shi
country: Japan
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city: Hiroshima-shi
country: Japan
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city: Iwakuni-shi
country: Japan
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city: Kitaadachi-gun
country: Japan
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city: Kitakyushu-shi
country: Japan
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city: Kurashiki shi
country: Japan
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city: Nagoya-shi
country: Japan
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city: Niigata-shi
country: Japan
facility: Research Site
city: Okayama-shi
country: Japan
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city: Osakasayama-shi
country: Japan
facility: Research Site
city: Toyoake-shi
country: Japan
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city: Wakayama-shi
country: Japan
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Seongnam-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: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Suwon
country: Korea, Republic of
facility: Research Site
city: Aguascalientes
country: Mexico
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country: Mexico
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city: Guadalajara
country: Mexico
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city: Monterrey
country: Mexico
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city: Monterrey
country: Mexico
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city: México
country: Mexico
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city: México
country: Mexico
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city: Pachuca de Soto
country: Mexico
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city: Arnhem
country: Netherlands
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city: Nijmegen
country: Netherlands
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city: Bellavista
country: Peru
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city: Lima
country: Peru
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city: Lima
country: Peru
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city: Lima
country: Peru
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city: Lima
country: Peru
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city: Davao City
country: Philippines
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city: Iloilo City
country: Philippines
facility: Research Site
city: Makati
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Warszawa
country: Poland
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city: Warszawa
country: Poland
facility: Research Site
city: Suceava
country: Romania
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Krasnoyarsk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Nizhniy Novgorod
country: Russian Federation
facility: Research Site
city: Obninsk
country: Russian Federation
facility: Research Site
city: Rostov-on-Don
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Tomsk
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Alicante
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Oviedo
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: San Sebastian
country: Spain
facility: Research Site
city: Santiago De Compostela (A Coruña)
country: Spain
facility: Research Site
city: Changhua
country: Taiwan
facility: Research Site
city: Taichung City
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Chiang Mai
country: Thailand
facility: Research Site
city: Chiang Rai
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
city: Lampang
country: Thailand
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
affiliation: UT MD Anderson Cancer Center
name: John Heymach, MD
role: PRINCIPAL_INVESTIGATOR
References: