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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01802632




Registration number
NCT01802632
Ethics application status
Date submitted
25/02/2013
Date registered
1/03/2013

Titles & IDs
Public title
AZD9291 First Time In Patients Ascending Dose Study
Scientific title
Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of AZD9291 in Patients With Advanced Non Small Cell Lung Cancer Who Progressed on Prior Therapy With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Agent
Secondary ID [1] 0 0
2012-004628-39
Secondary ID [2] 0 0
D5160C00001
Universal Trial Number (UTN)
Trial acronym
AURA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Non Small Cell Lung Cancer 0 0
Advanced (Inoperable) Non Small Cell Lung Cancer 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 - AZD9291

Experimental: Daily dose of AZD9291 - Daily oral dose of AZD9291


Treatment: Drugs: AZD9291
Starting dose 20 mg, administered once daily. If tolerated subsequent cohorts will test increasing doses of AZD9291, until a maximum tolerated dose or maximum feasible dose is defined

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

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) for Dose Expansion Population
Timepoint [1] 0 0
RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 21 months (at time of analysis)
Primary outcome [2] 0 0
Best Objective Response (BOR) for Dose Escalation Population
Timepoint [2] 0 0
RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 25 months (at time of analysis)
Primary outcome [3] 0 0
Objective Response Rate (ORR) for Extension Population
Timepoint [3] 0 0
RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 12 months (at the time of analysis)
Secondary outcome [1] 0 0
Duration of Response (DoR) for Dose Expansion Population
Timepoint [1] 0 0
RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 21 months (at time of analysis)
Secondary outcome [2] 0 0
Progression-Free Survival (PFS) for Dose Expansion Population
Timepoint [2] 0 0
RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 21 months (at time of analysis)
Secondary outcome [3] 0 0
Best Objective Response (BOR) for 80mg AZD9291 Extension Population
Timepoint [3] 0 0
RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 12 months (at the time of analysis)

Eligibility
Key inclusion criteria
* Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses
* Aged at least 18 years. Patients from Japan aged at least 20 years.
* Histological or cytological confirmation diagnosis of Non Small Cell Lung Cancer (NSCLC).
* Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI e.g. gefitinib or erlotinib (with the exception of 1st line expansion cohort). In addition other lines of therapy may have been given. All patients must have documented radiological progression on the last treatment administered prior to enrolling in the study.
* Patients (with the exception of 1st line expansion cohort) must fulfil one of the following:

* Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) OR
* Must have experienced clinical benefit from EGFR TKI, according to the Jackman criteria (Jackman et al 2010) followed by systemic objective progression (RECIST or WHO) while on continuous treatment with EGFR TKI.
* Previous treatment with a single-agent EGFR TKI (e.g. gefitinib or erlotinib).
* Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing or evidence of non-child bearing potential.
* Male patients should be willing to use barrier contraception.
* For 1st Line expansion cohort ONLY, confirmation that the tumour is EGFRm+ve and have had no prior therapy for their advanced disease (for 1st line patients biopsy will be at time of diagnosis of advanced disease).
* For dose expansion and extension cohorts, patients must also have confirmation of tumour T790M mutation status (confirmed positive or negative) from a biopsy sample taken after disease progression on the most recent treatment regimen (irrespective of whether this is EGFR TKI or chemotherapy).

Prior to entry a result from the central analysis of the patient's T790M mutation status must be obtained.

- World Health Organisation (WHO) performance status 0-1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks.
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Treatment with an EGFR TKI (erlotinib or gefitinib) within 8 days (approximately 5x half-life) of the first dose of study treatment.
* Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from the treatment of advanced NSCLC from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.
* AZD9291 in the present study (ie, dosing with AZD9291 previously initiated in this study).
* Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection.
* Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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 - Heidelberg
Recruitment hospital [2] 0 0
Research Site - Kogarah
Recruitment hospital [3] 0 0
Research Site - Nedlands
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
France
State/province [7] 0 0
Pierre Benite CEDEX
Country [8] 0 0
France
State/province [8] 0 0
Saint Herblain Cedex
Country [9] 0 0
France
State/province [9] 0 0
Villejuif
Country [10] 0 0
Germany
State/province [10] 0 0
Essen
Country [11] 0 0
Germany
State/province [11] 0 0
Köln
Country [12] 0 0
Germany
State/province [12] 0 0
Würzburg
Country [13] 0 0
Italy
State/province [13] 0 0
Genova
Country [14] 0 0
Italy
State/province [14] 0 0
Orbassano
Country [15] 0 0
Italy
State/province [15] 0 0
Roma
Country [16] 0 0
Japan
State/province [16] 0 0
Chiba-shi
Country [17] 0 0
Japan
State/province [17] 0 0
Fukuoka-shi
Country [18] 0 0
Japan
State/province [18] 0 0
Fukuoka
Country [19] 0 0
Japan
State/province [19] 0 0
Habikino-shi
Country [20] 0 0
Japan
State/province [20] 0 0
Hirakata-shi
Country [21] 0 0
Japan
State/province [21] 0 0
Hiroshima-shi
Country [22] 0 0
Japan
State/province [22] 0 0
Kanazawa
Country [23] 0 0
Japan
State/province [23] 0 0
Kashiwa
Country [24] 0 0
Japan
State/province [24] 0 0
Kobe-shi
Country [25] 0 0
Japan
State/province [25] 0 0
Matsuyama-shi
Country [26] 0 0
Japan
State/province [26] 0 0
Okayama-shi
Country [27] 0 0
Japan
State/province [27] 0 0
Shinjuku-ku
Country [28] 0 0
Japan
State/province [28] 0 0
Sunto-gun
Country [29] 0 0
Japan
State/province [29] 0 0
Takatsuki-shi
Country [30] 0 0
Japan
State/province [30] 0 0
Yokohama-shi
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Seoul
Country [32] 0 0
Spain
State/province [32] 0 0
Madrid
Country [33] 0 0
Spain
State/province [33] 0 0
Sevilla
Country [34] 0 0
Taiwan
State/province [34] 0 0
Tainan
Country [35] 0 0
Taiwan
State/province [35] 0 0
Taipei
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Manchester
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Newcastle upon Tyne

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
Yuri Rukazenkov
Address 0 0
AstraZeneca
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.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

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?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.