- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02094261
Phase II AZD9291 Open Label Study in NSCLC After Previous EGFR TKI Therapy in EGFR and T790M Mutation Positive Tumours (AURA2)
Phase II, Open Label, Single-arm Study to Assess Safety and Efficacy of AZD9291 in Patients With Locally Advanced/Metastatic NSCLC Whose Disease Has Progressed With Previous EGFR TKI and Whose Tumours Are EGFR and T790M Mutation Positive
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Alberta
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Edmonton, Alberta, Canada, T6G 1Z2
- Research Site
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Ontario
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Ottawa, Ontario, Canada, K1H 8L6
- Research Site
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Toronto, Ontario, Canada, M5G 2M9
- Research Site
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Hong Kong, Hong Kong
- Research Site
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Shatin, Hong Kong, 00000
- Research Site
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Milan, Italy, 20141
- Research Site
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Milano, Italy, 20132
- Research Site
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Napoli, Italy, 80131
- Research Site
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Perugia, Italy, 06132
- Research Site
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Verona, Italy, 37134
- Research Site
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Akashi-shi, Japan, 673-8558
- Research Site
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Chuo-ku, Japan, 104-0045
- Research Site
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Kitaadachi-gun, Japan, 362-0806
- Research Site
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Kitakyushu-shi, Japan, 802-0077
- Research Site
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Koto-ku, Japan, 135-8550
- Research Site
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Nagoya-shi, Japan, 464-8681
- Research Site
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Nagoya-shi, Japan, 460-0001
- Research Site
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Niigata-shi, Japan, 951-8566
- Research Site
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Osaka-shi, Japan, 541-8567
- Research Site
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Osaka-shi, Japan, 534-0021
- Research Site
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Osakasayama, Japan, 589-8511
- Research Site
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Sakai-shi, Japan, 591-8555
- Research Site
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Wakayama-shi, Japan, 641-8510
- Research Site
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Yokohama-shi, Japan, 236-0051
- Research Site
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Goyang-si, Korea, Republic of, 10408
- Research Site
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Seongnam-si, Korea, Republic of, 13620
- Research Site
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Seoul, Korea, Republic of, 06591
- Research Site
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A Coruña, Spain, 15006
- Research Site
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Barcelona, Spain, 08025
- Research Site
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Madrid, Spain, 28007
- Research Site
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Majadahonda, Spain, 28222
- Research Site
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Málaga, Spain, 29010
- Research Site
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Valencia, Spain, 46026
- Research Site
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Taichung, Taiwan, 40705
- Research Site
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Taipei, Taiwan, 112
- Research Site
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California
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La Jolla, California, United States, 92093
- Research Site
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Orange, California, United States, 92868
- Research Site
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Connecticut
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New Haven, Connecticut, United States, 06510
- Research Site
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Norwalk, Connecticut, United States, 06850
- Research Site
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Indiana
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Indianapolis, Indiana, United States, 46202
- Research Site
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Research Site
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New Hampshire
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Lebanon, New Hampshire, United States, 03756
- Research Site
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New York
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New York, New York, United States, 10032
- Research Site
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North Carolina
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Durham, North Carolina, United States, 27710
- Research Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion:
- Aged at least 18 years. Japan patients aged at least 20 years.
- Locally advanced/metastatic NSCLC not amenable to curative surgery or radiotherapy
- Radiological documentation of disease progression:
following 1st line EGFR TKI treatment but who have not received further treatment OR following prior therapy with an EGFR TKI and a platinum-based doublet chemotherapy. Patients who received prior EGFR TKI and platinum-based doublet chemotherapy may have also received additional lines of treatment. All patients must have documented radiological progression on the last treatment administered prior to enrolling in the study.
- Disease progression following 1st line EGFR TKI treatment or following prior EGFR TKI and platinum-containing doublet chemotherapy.
- Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q). Patients must have central confirmation of tumour T790M mutation positive status from a biopsy sample taken after confirmation of disease progression on the most recent treatment regimen.
- World Health Organisation (WHO) performance status 0-1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks.
- At least one lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline as ≥ 10mm in the longest diameter (except lymph nodes which must have short axis ≥ 15mm) with computerised tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements.
- Females of child-bearing potential using contraception; negative pregnancy test.
Exclusion:
- Treatment with an EGFR-TKI within 8 days of study entry; any cytotoxic chemotherapy, investigational agents or other anticancer drugs within 14 days of study entry; previous treatment with AZD9291 (or 3rd generation TKIs); major surgery within 4 weeks; radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks; current treatment with potent inhibitors of CYP2C8 and potent inhibitors/inducers of CYP3A4.
- Unresolved toxicities from prior therapy.
- Unstable spinal cord compression/brain metastases.
- Severe/uncontrolled systemic diseases, including uncontrolled hypertension, bleeding diatheses or infection.
- Refractory nausea/vomiting, chronic gastrointestinal diseases or bowel resection.
- Cardiac disease.
- Past history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
- Inadequate bone marrow reserve or organ function.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: AZD9291
Once daily tablet 80 mg
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Once daily tablet 80 mg
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Objective Response Rate (ORR)
Time Frame: RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)
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Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions.
ORR is the percentage of patients with at least 1 visit response of CR or PR (according to independent review) that was confirmed at least 4 weeks later, prior to progression or further anti-cancer therapy.
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RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Duration of Response (DoR)
Time Frame: RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)
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Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions.
DoR was defined as the time from the date of first documented response (CR or PR that was subsequently confirmed) until the date of documented progression (PD) or death in the absence of disease progression (by investigator assessment).
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RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)
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Disease Control Rate (DCR)
Time Frame: RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)
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Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions; Stable disease (SD): Neither sufficient shrinkage to qualify as a response nor sufficient growth to qualify as progression; Progressive Disease (PD): >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion.
DCR is the percentage of patients with best response of CR, PR or SD (according to independent review), prior to progression (PD) or further anti-cancer therapy.
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RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)
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Progression-Free Survival (PFS)
Time Frame: RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)
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Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Progressive Disease (PD): >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion.
PFS is the time from date of first dose until the date of PD (by independent review) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from AZD9291 therapy or received another anti-cancer therapy prior to progression.
Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST 1.1 assessment.
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RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Glenwood Goss, MD, 501 Smyth Road, Ottawa, Canada
- Principal Investigator: Tetsuya Mitsudomi, MD, Kinki University Hospital, Faculty of Medicine, Osaka, Japan
Publications and helpful links
General Publications
- 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.
- 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.
- Goss G, Tsai CM, Shepherd FA, Bazhenova L, Lee JS, Chang GC, Crino L, Satouchi M, Chu Q, Hida T, Han JY, Juan O, Dunphy F, Nishio M, Kang JH, Majem M, Mann H, Cantarini M, Ghiorghiu S, Mitsudomi T. Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2016 Dec;17(12):1643-1652. doi: 10.1016/S1470-2045(16)30508-3. Epub 2016 Oct 14.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Osimertinib
Other Study ID Numbers
- D5160C00002
- 2014-000531-17 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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