A Study of Osimertinib With or Without Chemotherapy Versus Chemotherapy Alone as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-Small Cell Lung Cancer

Non-Small Cell Lung Cancer Clinical Trial

— NeoADAURA  

Official title:

A Phase III, Randomised, Controlled, Multi-center, 3-Arm Study of Neoadjuvant Osimertinib as Monotherapy or in Combination With Chemotherapy Versus Standard of Care Chemotherapy Alone for the Treatment of Patients With Epidermal Growth Factor Receptor Mutation Positive, Resectable Non-small Cell Lung Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04351555
• Other study ID #: D516AC00001
• Secondary ID: 2020-000058-89
• Status: Recruiting
• Phase: Phase 3
• Start date: December 16, 2020
• Est. completion date: June 13, 2029

Study information

• Verified date: March 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase III, randomised, controlled, 3-arm, multi-centre study of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy, versus SoC chemotherapy alone, for the treatment of patients with resectable EGFRm Non-Small Cell Lung Cancer

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 328
• Est. completion date: June 13, 2029
• Est. primary completion date: July 5, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• Male or female, at least 18 years of age. For patients aged <20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative

• Histologically or cytologically documented non-squamous NSCLC with completely resectable (Stage II - IIIB N2) disease (according to Version 8 of the IASLC Cancer Staging Manual [IASLC Staging Manual in Thoracic Oncology 2016]).

• Complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by a MDT evaluation (which should include a thoracic surgeon, specialised in oncologic procedures).

• Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1 at enrolment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing

• A tumour which harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations (eg., T790M, G719X, Exon20 insertions, S7681 and L861Q).

Exclusion Criteria:

• Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.

• History of another primary malignancy (including any known or suspected synchronous primary lung cancer), except for the following: Malignancy treated with curative intent and with no known active disease =2 years before the first dose of investigational product (IP) and of low potential risk for recurrence; Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease; Adequately treated carcinoma in situ without evidence of disease; Any synchronous Stage IA primary lung cancer that is =2 cm and planned to be resected during surgery for the Stage II to IIIB N2 lung tumour.

• Patients who have pre-operative radiotherapy treatment as part of their care plan

• Mixed small cell and NSCLC histology

• Stages I, IIIB N3, IIIC, IVA, and IVB NSCLC

• T4 tumours infiltrating the great vessels, the carina, the trachea, the oesophagus, the heart, and/or the vertebral body; and/or any bulky N2 disease.

• Patients who are candidates to undergo only segmentectomies or wedge resections

• Prior treatment with any systemic anti-cancer therapy for NSCLC including chemotherapy, biologic therapy, immunotherapy, or any investigational drug

• Prior treatment with EGFR-TKI therapy

• Current use of (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP) 3A4 (at least 3 weeks prior)

Related Conditions & MeSH terms

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

Intervention

Drug:
• Osimertinib
Oral
• Cisplatin
Cisplatin (75mg/m2) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles.
• Carboplatin
Carboplatin (AUC5) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles
• Placebo
Oral
• Pemetrexed
Pemetrexed (500 mg/m2) to be administered with cisplatin or carboplatin on Day 1 of every 3-week cycle for 3 cycles

Locations

Country	Name	City	State
Austria	Research Site	Graz
Austria	Research Site	Linz
Austria	Research Site	Vienna
Austria	Research Site	Wien
Brazil	Research Site	Barretos
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Bento Goncalves
Brazil	Research Site	Fortaleza
Brazil	Research Site	Jau
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Recife
Brazil	Research Site	Ribeirão Preto
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Santa Maria
Brazil	Research Site	São José do Rio Preto
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	São Paulo
Bulgaria	Research Site	Panagyurishte
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Toronto	Ontario
Chile	Research Site	Concepcion
Chile	Research Site	Las Condes
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
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	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
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	Nanjing
China	Research Site	Nantong
China	Research Site	Shandong
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Shenzhen
China	Research Site	Suzhou
China	Research Site	Urumqi
China	Research Site	Wanzhou
China	Research Site	Wenzhou
China	Research Site	Xiamen
China	Research Site	Yangzhou
China	Research Site	Zhengzhou
France	Research Site	Angers
France	Research Site	Avignon Cedex
France	Research Site	Bordeaux
France	Research Site	Clermont Ferrand
France	Research Site	Lyon
France	Research Site	Toulon Cedex 9
Germany	Research Site	Berlin
Germany	Research Site	Bielefeld
Germany	Research Site	Esslingen a.N.
Germany	Research Site	Freiburg
Germany	Research Site	Gauting
Germany	Research Site	Georgsmarienhuette
Germany	Research Site	Halle
Germany	Research Site	Hamburg
Germany	Research Site	Heidelberg
Germany	Research Site	Homburg
Germany	Research Site	Köln
Germany	Research Site	Oldenburg
Germany	Research Site	Würzburg
India	Research Site	Delhi
India	Research Site	Kolkata
India	Research Site	Manipal
India	Research Site	Mumbai
India	Research Site	Mumbai
India	Research Site	Namakkal
India	Research Site	New Delhi
India	Research Site	Varanasi
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Kfar Saba
Israel	Research Site	Petah Tikva
Israel	Research Site	Ramat Gan
Israel	Research Site	Tel Aviv
Italy	Research Site	Bari
Italy	Research Site	Firenze
Italy	Research Site	Monza
Italy	Research Site	Orbassano
Italy	Research Site	Padova
Italy	Research Site	Roma
Italy	Research Site	Rozzano
Italy	Research Site	Varese
Japan	Research Site	Akashi-shi
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Chiba-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Kashiwa
Japan	Research Site	Koto-ku
Japan	Research Site	Kyoto-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama-shi
Japan	Research Site	Sakai-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Sunto-gun
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Hwasun-gun
Korea, Republic of	Research Site	Incheon
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	Yangsan-si
Mexico	Research Site	Aguascalientes
Mexico	Research Site	D.F
Mexico	Research Site	Mexico City
Mexico	Research Site	Mexico City
Peru	Research Site	La Libertad
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Poland	Research Site	Bialystok
Poland	Research Site	Kraków
Poland	Research Site	Olsztyn
Poland	Research Site	Otwock
Poland	Research Site	Poznan
Poland	Research Site	Szczecin
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Krasnoyarsk
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	Perm
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	Tomsk
Singapore	Research Site	Singapore
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda
Spain	Research Site	Málaga
Switzerland	Research Site	Bellinzona
Switzerland	Research Site	Winterthur
Switzerland	Research Site	Zürich
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan City
Taiwan	Research Site	Taipei
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	Khon Kaen
Thailand	Research Site	Pathumthani
Thailand	Research Site	Pathumwan
Thailand	Research Site	Phisanulok
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Malatya
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	Manchester
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boston	Massachusetts
United States	Research Site	Chicago	Illinois
United States	Research Site	Commack	New York
United States	Research Site	Duarte	California
United States	Research Site	Fairfax	Virginia
United States	Research Site	Houston	Texas
United States	Research Site	Irvine	California
United States	Research Site	Lebanon	New Hampshire
United States	Research Site	Los Angeles	California
United States	Research Site	Miami	Florida
United States	Research Site	New Haven	Connecticut
United States	Research Site	New York	New York
United States	Research Site	San Antonio	Texas
United States	Research Site	San Francisco	California
United States	Research Site	Santa Monica	California
United States	Research Site	Santa Rosa	California
United States	Research Site	Seattle	Washington
United States	Research Site	Washington	District of Columbia
Vietnam	Research Site	Hanoi
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,  Austria,  Brazil,  Bulgaria,  Canada,  Chile,  China,  France,  Germany,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Peru,  Poland,  Russian Federation,  Singapore,  Spain,  Switzerland,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cure rate	The cure rate is defined as the percentage of people in this study who are still alive and disease free for a certain period of time after they finished the surgery. Here 5-year landmark cure rate will be calculated in the same time as OS analysis.	From the surgery until 5 years after surgery
Other	Number of adverse events as assessed by CTCAE 5.0 and other clinical variables for safety and tolerability profile of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy prior to surgery compared with chemotherapy alone	Other clinical variables include deaths, laboratory data, vital signs (pulse and BP), ECG, LVEF, ECOG performance status, and ophthalmologic assessment	From the time of enrollment to either 28-days after the last dose of last study treatment for patients who do not undergo surgery, or 90-days post-surgery
Other	MPR using plasma-derived circulating-free tumour DNA (ctDNA)		From date of randomization to an average of 12 weeks after the first dose
Primary	Major Pathological Response (MPR)	Defined as =10% residual cancer cells in the main tumour, as assessed per central pathology laboratory post-surgery	From date of randomization to an average of 12 weeks after the first dose
Secondary	Pathological complete response (pCR)	Defined as absence of any viable cancer cells in the dissected tumour samples, including the main tumour, lymph nodes, and margins as assessed per central pathology laboratory post-surgery	From date of randomization to an average of 12 weeks after the first dose
Secondary	Event-free survival (EFS)	An event is defined as documented disease progression that precludes surgery or prevents completion of definitive surgery; recurrence or a new lesion, local or distant (a new primary malignancy, confirmed by pathology if clinically feasible, is not considered to be an EFS event); death due to any cause	From date of randomization up to approximately 5.5 years after the last patient is randomized
Secondary	Overall Survival (OS)	OS will be defined as the time from the date of randomisation until death due to any cause	From date of randomization up to approximately 5.5 years after the last patient is randomized
Secondary	Disease free survival (DFS)	DFS is defined as the time from the date of surgery until the first date of disease recurrence (local or distant) or date of death due to any cause, whichever occurs first.	From date of randomization up to approximately 5.5 years after the last patient is randomized
Secondary	Downstaging	Measured using pathologic mediastinal lymph node evaluation	From date of randomization to an average of 12 weeks after the first dose
Secondary	Difference between treatment arms in change from baseline in EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 items)	Assess disease-related symptoms, functioning, and global health status/quality-of-life in patients	From date of randomization up to approximately 5.5 years after the last patient is randomized
Secondary	Concordance of EGFRm status between tumour tissue DNA and patient-matched plasma-derived ctDNA		Baseline
Secondary	Corcordance of EGFR mutation status between the local and central cobas EGFR mutation test results from baseline tumour samples		Baseline
Secondary	PK plasma concentrations of osimertinib		From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days)
Secondary	Difference between treatment arms in change from baseline in EORTC QLQ-LC13 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 items)	Assess lung cancer-associated symptoms and side effects from conventional chemotherapy and radiotherapy	From date of randomization up to approximately 5.5 years after the last patient is randomized