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Trial record 1 of 2 for:    AURA-3
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AZD9291 Versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (AURA3)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02151981
First Posted: June 2, 2014
Last Update Posted: December 5, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
AstraZeneca
  Purpose
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

Condition Intervention Phase
Anticancer Treatment Drug: Chemotherapy Drug: Cross-over to AZD9291 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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).

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Progression Free Survival (PFS) by Investigator Assessment [ Time Frame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 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 randomisation until the date of PD (by investigator assessment) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised 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.


Secondary Outcome Measures:
  • Objective Response Rate (ORR) by Investigator Assessment [ Time Frame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 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 prior to progression or any further therapy.

  • Duration of Response (DoR) by Investigator Assessment [ Time Frame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 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 is the time from the date of first documented response until the date of documented progression or death in the absence of disease progression.

  • Disease Control Rate (DCR) by Investigator Assessment [ Time Frame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 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 at >=6 weeks, prior to any progressive disease (PD).

  • Tumour Shrinkage by Investigator Assessment [ Time Frame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of analysis). ]
    Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Tumour size was calculated as the sum of the longest diameters (SLD) of the Target Lesions. Tumour shrinkage is percentage change in tumour size from baseline using RECIST v1.1 tumour response.


Other Outcome Measures:
  • Number of Deaths [ Time Frame: From randomisation until death, up to 19 months (at the time of analysis). ]
    Total number of deaths at the time of the analysis


Enrollment: 419
Actual Study Start Date: August 4, 2014
Estimated Study Completion Date: November 30, 2018
Primary Completion Date: April 15, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AZD9291
AZD9291 80 mg, orally, once daily
Drug: Chemotherapy
Randomization to either AZD9291 or platinum-based doublet-chemotherapy on Day 1 of every 21d cycle in a 2:1 (AZD9291:platinum-based doublet-chemotherapy) ratio
Other Names:
  • AZD9291
  • Platinum-based Doublet-Chemotherapy
Drug: Cross-over to AZD9291

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 AZD9291 80mg, once daily. These subjects may continue treatment with AZD9291 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 AZD9291.

Active Comparator: Platinum-based doublet chemotherapy
pemetrexed 500mg/m2 + carboplatin AUC5 or pemetrexed 500mg/m2 + cisplatin 75mg/m2
Drug: Chemotherapy
Randomization to either AZD9291 or platinum-based doublet-chemotherapy on Day 1 of every 21d cycle in a 2:1 (AZD9291:platinum-based doublet-chemotherapy) ratio
Other Names:
  • AZD9291
  • Platinum-based Doublet-Chemotherapy

Detailed Description:
This is a phase III, open label, randomized study assessing AZD9291 (80 mg, orally, once daily) versus platinum-based doublet chemotherapy (standard of care) in subjects with confirmed diagnosis of Epidermal Growth Factor Receptor (EGFR) mutation positive NSCLC, who have progressed following prior therapy with an approved Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) agent and whose tumours harbour a T790M mutation within the EGFR Gene. Subjects must be chemotherapy naive and must agree to provide a biopsy for central confirmation of T790 mutation status following confirmed disease progression on their first line EGFR-TKI treatment (e.g. erlotinib, gefitinib or afatinib). Suitable subjects will then be randomized to receive either AZD9291 (80mg orally, once daily) or platinum-based doublet chemotherapy (pemetrexed 500 mg/m2 + carboplatin area under the plasma concentration-time curve AUC 5 or pemetrexed 500 mg/m2 + cisplatin 75 mg/m2) on Day 1 of every 21-day cycle in a 2:1 (AZD9291: platinum-based doublet chemotherapy) ratio. 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 AZD9291 80mg, once daily. These subjects may continue treatment with AZD9291 even after disease progression, as long as they are continuing to show clinical benefit, as judged by the investigator. The primary objective of the study is to assess the efficacy of AZD9291 compared with platinum-based doublet chemotherapy by assessment of Progression Free Survival (PFS), using investigator assessments according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1), as well as asensitivity analysis of Progression Free Survival using Blinded Independent Central Review (BICR).
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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 AZD9291, or a 3rd generation EGFR TKI

For subjects who cross-over to AZD9291:

  • 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02151981


  Show 149 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Tony Mok, MD Department of Clinical Oncology, The Chinese University of Hong Kong
Principal Investigator: Yilong Wu, MD Guangdong General Hospital, Guangdong, 510030, China
Principal Investigator: Vassiliki A Papadimitrakopoulou, MD The University of Texas/M.D. Anderson Cancer Center, Houston, Tx, USA
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02151981     History of Changes
Other Study ID Numbers: D5160C00003
First Submitted: May 15, 2014
First Posted: June 2, 2014
Results First Submitted: April 12, 2017
Results First Posted: July 21, 2017
Last Update Posted: December 5, 2017
Last Verified: October 2017

Keywords provided by AstraZeneca:
Advanced Non-Small Cell Lung Cancer; T790M Mutation Positive

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action