The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02151981




Registration number
NCT02151981
Ethics application status
Date submitted
15/05/2014
Date registered
2/06/2014

Titles & IDs
Public title
AZD9291 (Osimertinib) Versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Scientific title
A Phase III, Open Label, Randomized Study of AZD9291 Versus Platinum-Based Doublet Chemotherapy for Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Whose Disease Has Progressed With Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Whose Tumours Harbour a T790M Mutation Within the Epidermal Growth Factor Receptor Gene (AURA3).
Secondary ID [1] 0 0
2014-000594-39
Secondary ID [2] 0 0
D5160C00003
Universal Trial Number (UTN)
Trial acronym
AURA3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anticancer Treatment 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Chemotherapy
Treatment: Drugs - Cross-over to Osimertinib

Experimental: Osimertinib - Osimertinib 80 mg, orally, once daily

Active comparator: Platinum-based doublet chemotherapy - pemetrexed 500mg/m2 + carboplatin AUC5 or pemetrexed 500mg/m2 + cisplatin 75mg/m2


Treatment: Drugs: Chemotherapy
Randomization to either Osimertinib or platinum-based doublet-chemotherapy on Day 1 of every 21d cycle in a 2:1 (Osimertinib:platinum-based doublet-chemotherapy) ratio

Treatment: Drugs: Cross-over to Osimertinib
Once subjects on the platinum-based doublet chemotherapy arm are determined to have objective radiological progression according to RECIST 1.1 by the investigator and confirmed by independent central imaging review, they will be given the opportunity to begin treatment with Osimertinib 80mg, once daily. These subjects may continue treatment with Osimertinib even after disease progression, as long as they are continuing to show clinical benefit, as judged by the investigator.

Subjects who stop platinum-based doublet chemotherapy for reasons other than objective disease progression according to RECIST 1.1 will not be eligible to cross-over to Osimertinib.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) by Investigator Assessment
Timepoint [1] 0 0
RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Secondary outcome [1] 0 0
Objective Response Rate (ORR) by Investigator Assessment
Timepoint [1] 0 0
RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Secondary outcome [2] 0 0
Duration of Response (DoR) by Investigator Assessment
Timepoint [2] 0 0
RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Secondary outcome [3] 0 0
Disease Control Rate (DCR) by Investigator Assessment
Timepoint [3] 0 0
RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Secondary outcome [4] 0 0
Tumour Shrinkage by Investigator Assessment
Timepoint [4] 0 0
RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Secondary outcome [5] 0 0
Secondary: Overall Survival (OS)
Timepoint [5] 0 0
From date of randomization until time of final OS analysis, a median follow-up of 43 months

Eligibility
Key inclusion criteria
* Subjects with histologically or cytologically documented NSCLC.
* Locally advanced or metastatic NSCLC
* Radiological documentation of disease progression following 1st line EGFR TKI Treatment without any further treatment
* Eligible to receive treatment with the selected doublet-chemotherapy
* Central confirmation of T790M+ mutation status
* World Health Organization (WHO) performance status 0-1
* At least one lesion, not previously irradiated.
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* • Prior neo-adjuvant or adjuvant chemotherapy treatment within 6 months prior of starting 1st EGFR TKI treatment
* Treatment with more than one prior line of treatment for advanced NSCLC
* Treatment with an approved EGFR-TKI (e.g.,erlotinib, gefitinib, afatinib) within 8 days or approximately 5x half-life of the first dose of study treatment
* Any investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment
* Previous treatment with Osimertinib, or a 3rd generation EGFR TKI

For subjects who cross-over to Osimertinib:

* Once subjects on the platinum-based doublet chemotherapy arm are determined to have objective radiological progression according to RECIST 1.1 by the investigator and confirmed by independent central imaging review.
* At least 14 days since last dose of platinum-based doublet chemotherapy

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Darlinghurst
Recruitment hospital [2] 0 0
Research Site - Heidelberg
Recruitment hospital [3] 0 0
Research Site - Kogarah
Recruitment hospital [4] 0 0
Research Site - Nedlands
Recruitment hospital [5] 0 0
Research Site - Woolloongabba
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment postcode(s) [5] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
New Hampshire
Country [10] 0 0
United States of America
State/province [10] 0 0
New Jersey
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
South Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
United States of America
State/province [16] 0 0
Wisconsin
Country [17] 0 0
Canada
State/province [17] 0 0
Alberta
Country [18] 0 0
Canada
State/province [18] 0 0
British Columbia
Country [19] 0 0
Canada
State/province [19] 0 0
Nova Scotia
Country [20] 0 0
Canada
State/province [20] 0 0
Ontario
Country [21] 0 0
Canada
State/province [21] 0 0
Quebec
Country [22] 0 0
China
State/province [22] 0 0
Beijing
Country [23] 0 0
China
State/province [23] 0 0
Changchun
Country [24] 0 0
China
State/province [24] 0 0
Chongqing
Country [25] 0 0
China
State/province [25] 0 0
Fuzhou
Country [26] 0 0
China
State/province [26] 0 0
Guangzhou
Country [27] 0 0
China
State/province [27] 0 0
Hangzhou
Country [28] 0 0
China
State/province [28] 0 0
Harbin
Country [29] 0 0
China
State/province [29] 0 0
Nanchang
Country [30] 0 0
China
State/province [30] 0 0
Shanghai
Country [31] 0 0
China
State/province [31] 0 0
Tianjin
Country [32] 0 0
China
State/province [32] 0 0
Zhengzhou
Country [33] 0 0
China
State/province [33] 0 0
Ürümqi
Country [34] 0 0
France
State/province [34] 0 0
Clermont Ferrand
Country [35] 0 0
France
State/province [35] 0 0
Dijon
Country [36] 0 0
France
State/province [36] 0 0
Lille
Country [37] 0 0
France
State/province [37] 0 0
Marseille Cedex 20
Country [38] 0 0
France
State/province [38] 0 0
Paris
Country [39] 0 0
France
State/province [39] 0 0
Strasbourg Cedex
Country [40] 0 0
France
State/province [40] 0 0
Toulouse Cedex 09
Country [41] 0 0
France
State/province [41] 0 0
Villejuif
Country [42] 0 0
Germany
State/province [42] 0 0
Essen
Country [43] 0 0
Germany
State/province [43] 0 0
Frankfurt
Country [44] 0 0
Germany
State/province [44] 0 0
Gerlingen
Country [45] 0 0
Germany
State/province [45] 0 0
Oldenburg
Country [46] 0 0
Germany
State/province [46] 0 0
Regensburg
Country [47] 0 0
Germany
State/province [47] 0 0
Würzburg
Country [48] 0 0
Hong Kong
State/province [48] 0 0
Hong Kong
Country [49] 0 0
Hong Kong
State/province [49] 0 0
Shatin
Country [50] 0 0
Hungary
State/province [50] 0 0
Budapest
Country [51] 0 0
Italy
State/province [51] 0 0
Avellino
Country [52] 0 0
Italy
State/province [52] 0 0
Meldola
Country [53] 0 0
Italy
State/province [53] 0 0
Milano
Country [54] 0 0
Italy
State/province [54] 0 0
Orbassano
Country [55] 0 0
Italy
State/province [55] 0 0
Roma
Country [56] 0 0
Japan
State/province [56] 0 0
Akashi-shi
Country [57] 0 0
Japan
State/province [57] 0 0
Bunkyo-ku
Country [58] 0 0
Japan
State/province [58] 0 0
Fukuoka
Country [59] 0 0
Japan
State/province [59] 0 0
Hirakata-shi
Country [60] 0 0
Japan
State/province [60] 0 0
Kanazawa
Country [61] 0 0
Japan
State/province [61] 0 0
Kitaadachi-gun
Country [62] 0 0
Japan
State/province [62] 0 0
Kobe-shi
Country [63] 0 0
Japan
State/province [63] 0 0
Kurashiki-shi
Country [64] 0 0
Japan
State/province [64] 0 0
Kyoto-shi
Country [65] 0 0
Japan
State/province [65] 0 0
Matsuyama-shi
Country [66] 0 0
Japan
State/province [66] 0 0
Nagoya-shi
Country [67] 0 0
Japan
State/province [67] 0 0
Natori-shi
Country [68] 0 0
Japan
State/province [68] 0 0
Niigata-shi
Country [69] 0 0
Japan
State/province [69] 0 0
Okayama-shi
Country [70] 0 0
Japan
State/province [70] 0 0
Osaka-shi
Country [71] 0 0
Japan
State/province [71] 0 0
Osakasayama
Country [72] 0 0
Japan
State/province [72] 0 0
Sakai-shi
Country [73] 0 0
Japan
State/province [73] 0 0
Shinjuku-ku
Country [74] 0 0
Japan
State/province [74] 0 0
Sunto-gun
Country [75] 0 0
Japan
State/province [75] 0 0
Takatsuki-shi
Country [76] 0 0
Japan
State/province [76] 0 0
Wakayama-shi
Country [77] 0 0
Japan
State/province [77] 0 0
Yokohama-shi
Country [78] 0 0
Korea, Republic of
State/province [78] 0 0
Busan
Country [79] 0 0
Korea, Republic of
State/province [79] 0 0
Cheongju-si
Country [80] 0 0
Korea, Republic of
State/province [80] 0 0
Goyang-si
Country [81] 0 0
Korea, Republic of
State/province [81] 0 0
Incheon
Country [82] 0 0
Korea, Republic of
State/province [82] 0 0
Jinju-si
Country [83] 0 0
Korea, Republic of
State/province [83] 0 0
Seongnam-si
Country [84] 0 0
Korea, Republic of
State/province [84] 0 0
Seoul
Country [85] 0 0
Korea, Republic of
State/province [85] 0 0
Suwon-si
Country [86] 0 0
Korea, Republic of
State/province [86] 0 0
Ulsan
Country [87] 0 0
Mexico
State/province [87] 0 0
Mexico
Country [88] 0 0
Mexico
State/province [88] 0 0
Oaxaca
Country [89] 0 0
Netherlands
State/province [89] 0 0
Amsterdam
Country [90] 0 0
Netherlands
State/province [90] 0 0
Groningen
Country [91] 0 0
Russian Federation
State/province [91] 0 0
Ekaterinburg
Country [92] 0 0
Russian Federation
State/province [92] 0 0
Moscow
Country [93] 0 0
Russian Federation
State/province [93] 0 0
Omsk
Country [94] 0 0
Russian Federation
State/province [94] 0 0
Saint Petersburg,
Country [95] 0 0
Russian Federation
State/province [95] 0 0
Saint Petersburg
Country [96] 0 0
Russian Federation
State/province [96] 0 0
Saint-Petersburg
Country [97] 0 0
Spain
State/province [97] 0 0
Madrid
Country [98] 0 0
Spain
State/province [98] 0 0
Málaga
Country [99] 0 0
Spain
State/province [99] 0 0
Sevilla
Country [100] 0 0
Spain
State/province [100] 0 0
Zaragoza
Country [101] 0 0
Sweden
State/province [101] 0 0
Göteborg
Country [102] 0 0
Sweden
State/province [102] 0 0
Lund
Country [103] 0 0
Sweden
State/province [103] 0 0
Stockholm
Country [104] 0 0
Taiwan
State/province [104] 0 0
Changhua
Country [105] 0 0
Taiwan
State/province [105] 0 0
Hsinchu
Country [106] 0 0
Taiwan
State/province [106] 0 0
Kaohsiung City
Country [107] 0 0
Taiwan
State/province [107] 0 0
Kaohsiung
Country [108] 0 0
Taiwan
State/province [108] 0 0
Taichung
Country [109] 0 0
Taiwan
State/province [109] 0 0
Tainan
Country [110] 0 0
Taiwan
State/province [110] 0 0
Taipei
Country [111] 0 0
Taiwan
State/province [111] 0 0
Taoyuan
Country [112] 0 0
United Kingdom
State/province [112] 0 0
Aberdeen
Country [113] 0 0
United Kingdom
State/province [113] 0 0
Bristol
Country [114] 0 0
United Kingdom
State/province [114] 0 0
Glasgow
Country [115] 0 0
United Kingdom
State/province [115] 0 0
Huddersfield
Country [116] 0 0
United Kingdom
State/province [116] 0 0
London
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Manchester
Country [118] 0 0
United Kingdom
State/province [118] 0 0
Newcastle-Upon-Tyne
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Nottingham
Country [120] 0 0
United Kingdom
State/province [120] 0 0
Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Yilong Wu, MD
Address 0 0
Guangdong General Hospital, Guangdong, 510030, China
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available to whom?
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.