Phase II AZD9291 Open Label Study in NSCLC After Previous EGFR TKI Therapy in EGFR and T790M Mutation Positive Tumours (AURA2)

November 5, 2024 updated by: AstraZeneca

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

A Phase II, Open Label, Single-arm Study to Assess the Safety and Efficacy of AZD9291 in Patients with Locally Advanced/Metastatic Non Small Cell Lung Cancer whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours are Epidermal Growth Factor Receptor Mutation and T790M Mutation Positive

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a phase II, open label, single arm study assessing the safety and efficacy of AZD9291 (80 mg, orally, once daily) in patients with a confirmed diagnosis of Epidermal Growth Factor Receptor mutation positive and T790M mutation positive NSCLC,who have progressed following prior therapy with an approved Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) agent. Patients must agree to provide a biopsy for central confirmation of T790M mutation status following confirmed disease progression on the most recent treatment regimen. The primary objective of the study is to assess the efficacy of AZD9291 by assessment of Objective Response Rate according to RECIST 1.1 by an Independent Central Review.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
210

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Research Site
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • Research Site
      • Toronto, Ontario, Canada, M5G 2M9
        • Research Site
  • Hong Kong
      • Hong Kong, Hong Kong
        • Research Site
      • Shatin, Hong Kong, 00000
        • Research Site
  • Italy
      • Milan, Italy, 20141
        • Research Site
      • Milano, Italy, 20132
        • Research Site
      • Napoli, Italy, 80131
        • Research Site
      • Perugia, Italy, 06132
        • Research Site
      • Verona, Italy, 37134
        • Research Site
  • Japan
      • Akashi-shi, Japan, 673-8558
        • Research Site
      • Chuo-ku, Japan, 104-0045
        • Research Site
      • Kitaadachi-gun, Japan, 362-0806
        • Research Site
      • Kitakyushu-shi, Japan, 802-0077
        • Research Site
      • Koto-ku, Japan, 135-8550
        • Research Site
      • Nagoya-shi, Japan, 464-8681
        • Research Site
      • Nagoya-shi, Japan, 460-0001
        • Research Site
      • Niigata-shi, Japan, 951-8566
        • Research Site
      • Osaka-shi, Japan, 541-8567
        • Research Site
      • Osaka-shi, Japan, 534-0021
        • Research Site
      • Osakasayama, Japan, 589-8511
        • Research Site
      • Sakai-shi, Japan, 591-8555
        • Research Site
      • Wakayama-shi, Japan, 641-8510
        • Research Site
      • Yokohama-shi, Japan, 236-0051
        • Research Site
  • Korea, Republic of
      • Goyang-si, Korea, Republic of, 10408
        • Research Site
      • Seongnam-si, Korea, Republic of, 13620
        • Research Site
      • Seoul, Korea, Republic of, 06591
        • Research Site
  • Spain
      • A Coruña, Spain, 15006
        • Research Site
      • Barcelona, Spain, 08025
        • Research Site
      • Madrid, Spain, 28007
        • Research Site
      • Majadahonda, Spain, 28222
        • Research Site
      • Málaga, Spain, 29010
        • Research Site
      • Valencia, Spain, 46026
        • Research Site
  • Taiwan
      • Taichung, Taiwan, 40705
        • Research Site
      • Taipei, Taiwan, 112
        • Research Site
  • United States
    • California
      • La Jolla, California, United States, 92093
        • Research Site
      • Orange, California, United States, 92868
        • Research Site
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Research Site
      • Norwalk, Connecticut, United States, 06850
        • Research Site
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Research Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Research Site
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Research Site
    • New York
      • New York, New York, United States, 10032
        • Research Site
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 130 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: AZD9291
Once daily tablet 80 mg
Drug: AZD9291
Once daily tablet 80 mg

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
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.
RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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)
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).
RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)
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)
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.
RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)
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)
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.
RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AstraZeneca

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 20, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 7, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 17, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 20, 2014

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 21, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 6, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • D5160C00002
  • 2014-000531-17 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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

IPD Sharing Time Frame

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

IPD Sharing Access Criteria

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

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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