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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02151981




Registration number
NCT02151981
Ethics application status
Date submitted
15/05/2014
Date registered
2/06/2014
Date last updated
13/09/2023

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
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Nottingham
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Wolverhampton

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

Ethics approval
Ethics application status

Summary
Brief summary
A Phase III, Open Label, Randomized Study of Osimertinib 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
Trial website
https://clinicaltrials.gov/ct2/show/NCT02151981
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02151981