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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
Date last updated
18/01/2024

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
Not applicable
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
4/03/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/12/2023
Sample size
Target
Accrual to date
Final
603
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
This study will treat patients with advanced NSCLC who have already received at least one course of specific anti-cancer treatment but the tumour has started to re-grow following that treatment. This is the first time this drug has ever been tested in patients, and so it will help to understand what type of side effects may occur with the drug treatment, it will measure the levels of drug in the body, it will also measure the anti-cancer activity. By using these pieces of information together the best dose of this drug to use in further clinical trials will be selected.
Trial website
https://clinicaltrials.gov/study/NCT01802632
Trial related presentations / publications
Martin ML, Correll J, Walding A, Ryden A. How patients being treated for non-small cell lung cancer value treatment benefit despite side effects. Qual Life Res. 2022 Jan;31(1):135-146. doi: 10.1007/s11136-021-02882-6. Epub 2021 May 31.
Ahn MJ, Han JY, Kim DW, Cho BC, Kang JH, Kim SW, Yang JC, Mitsudomi T, Lee JS. Osimertinib in Patients with T790M-Positive Advanced Non-small Cell Lung Cancer: Korean Subgroup Analysis from Phase II Studies. Cancer Res Treat. 2020 Jan;52(1):284-291. doi: 10.4143/crt.2019.200. Epub 2019 Jul 23.
Ahn MJ, Tsai CM, Shepherd FA, Bazhenova L, Sequist LV, Hida T, Yang JCH, Ramalingam SS, Mitsudomi T, Janne PA, Mann H, Cantarini M, Goss G. Osimertinib in patients with T790M mutation-positive, advanced non-small cell lung cancer: Long-term follow-up from a pooled analysis of 2 phase 2 studies. Cancer. 2019 Mar 15;125(6):892-901. doi: 10.1002/cncr.31891. Epub 2018 Dec 4.
Oxnard GR, Hu Y, Mileham KF, Husain H, Costa DB, Tracy P, Feeney N, Sholl LM, Dahlberg SE, Redig AJ, Kwiatkowski DJ, Rabin MS, Paweletz CP, Thress KS, Janne PA. Assessment of Resistance Mechanisms and Clinical Implications in Patients With EGFR T790M-Positive Lung Cancer and Acquired Resistance to Osimertinib. JAMA Oncol. 2018 Nov 1;4(11):1527-1534. doi: 10.1001/jamaoncol.2018.2969.
Kiura K, Yoh K, Katakami N, Nogami N, Kasahara K, Takahashi T, Okamoto I, Cantarini M, Hodge R, Uchida H. Osimertinib in patients with epidermal growth factor receptor T790M advanced non-small cell lung cancer selected using cytology samples. Cancer Sci. 2018 Apr;109(4):1177-1184. doi: 10.1111/cas.13511. Epub 2018 Feb 27.
Goss G, Tsai CM, Shepherd FA, Ahn MJ, Bazhenova L, Crino L, de Marinis F, Felip E, Morabito A, Hodge R, Cantarini M, Johnson M, Mitsudomi T, Janne PA, Yang JC. CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. Ann Oncol. 2018 Mar 1;29(3):687-693. doi: 10.1093/annonc/mdx820.
Ramalingam SS, Yang JC, Lee CK, Kurata T, Kim DW, John T, Nogami N, Ohe Y, Mann H, Rukazenkov Y, Ghiorghiu S, Stetson D, Markovets A, Barrett JC, Thress KS, Janne PA. Osimertinib As First-Line Treatment of EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2018 Mar 20;36(9):841-849. doi: 10.1200/JCO.2017.74.7576. Epub 2017 Aug 25.
Thress KS, Jacobs V, Angell HK, Yang JC, Sequist LV, Blackhall F, Su WC, Schuler M, Wolf J, Gold KA, Cantarini M, Barrett JC, Janne PA. Modulation of Biomarker Expression by Osimertinib: Results of the Paired Tumor Biopsy Cohorts of the AURA Phase I Trial. J Thorac Oncol. 2017 Oct;12(10):1588-1594. doi: 10.1016/j.jtho.2017.07.011. Epub 2017 Jul 24.
Dearden S, Brown H, Jenkins S, Thress KS, Cantarini M, Cole R, Ranson M, Janne PA. EGFR T790M mutation testing within the osimertinib AURA Phase I study. Lung Cancer. 2017 Jul;109:9-13. doi: 10.1016/j.lungcan.2017.04.011. Epub 2017 Apr 19.
Ballard P, Yates JW, Yang Z, Kim DW, Yang JC, Cantarini M, Pickup K, Jordan A, Hickey M, Grist M, Box M, Johnstrom P, Varnas K, Malmquist J, Thress KS, Janne PA, Cross D. Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity. Clin Cancer Res. 2016 Oct 15;22(20):5130-5140. doi: 10.1158/1078-0432.CCR-16-0399. Epub 2016 Jul 19.
Oxnard GR, Thress KS, Alden RS, Lawrance R, Paweletz CP, Cantarini M, Yang JC, Barrett JC, Janne PA. Association Between Plasma Genotyping and Outcomes of Treatment With Osimertinib (AZD9291) in Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2016 Oct 1;34(28):3375-82. doi: 10.1200/JCO.2016.66.7162. Epub 2016 Jun 27.
Thress KS, Brant R, Carr TH, Dearden S, Jenkins S, Brown H, Hammett T, Cantarini M, Barrett JC. EGFR mutation detection in ctDNA from NSCLC patient plasma: A cross-platform comparison of leading technologies to support the clinical development of AZD9291. Lung Cancer. 2015 Dec;90(3):509-15. doi: 10.1016/j.lungcan.2015.10.004. Epub 2015 Oct 9.
Kim TM, Song A, Kim DW, Kim S, Ahn YO, Keam B, Jeon YK, Lee SH, Chung DH, Heo DS. Mechanisms of Acquired Resistance to AZD9291: A Mutation-Selective, Irreversible EGFR Inhibitor. J Thorac Oncol. 2015 Dec;10(12):1736-44. doi: 10.1097/JTO.0000000000000688.
Yu HA, Tian SK, Drilon AE, Borsu L, Riely GJ, Arcila ME, Ladanyi M. Acquired Resistance of EGFR-Mutant Lung Cancer to a T790M-Specific EGFR Inhibitor: Emergence of a Third Mutation (C797S) in the EGFR Tyrosine Kinase Domain. JAMA Oncol. 2015 Oct;1(7):982-4. doi: 10.1001/jamaoncol.2015.1066. No abstract available.
Janne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, Ahn MJ, Kim SW, Su WC, Horn L, Haggstrom D, Felip E, Kim JH, Frewer P, Cantarini M, Brown KH, Dickinson PA, Ghiorghiu S, Ranson M. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 2015 Apr 30;372(18):1689-99. doi: 10.1056/NEJMoa1411817.
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01802632