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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:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02151981
First received: May 15, 2014
Last updated: January 23, 2017
Last verified: January 2017
  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: No masking
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) [ Time Frame: At baseline and every 6 weeks from randomization until progression (up to approximately 12 months) ]
    To assess the efficacy of AZD9291 compared with platinum-based doublet chemotherapy by assessment of Progression Free Survival using investigator assessment according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1)


Secondary Outcome Measures:
  • Objective Response Rate (ORR) [ Time Frame: At baseline and every 6 weeks from randomization until progression (up to approximately 12 months) ]
    To assess the efficacy of AZD9291 compared with platinum-based doublet chemotherapy by assessment of Objective Response Rate (ORR) using investigator assessment according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1).

  • Duration of Response (DoR) [ Time Frame: At baseline and every 6 weeks from randomization until progression (up to approximately 12 months) ]
    To assess the efficacy of AZD9291 compared with platinum-based doublet chemotherapy by assessment of Duration of Response (DoR) using investigator assessment according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1).

  • Disease Control Rate (DCR) [ Time Frame: At baseline and every 6 weeks from randomization until progression (up to approximately 12 months) ]
    To assess the efficacy of AZD9291 compared with platinum-based doublet chemotherapy by assessment of Disease Control Rate (DCR) using investigator assessment according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1).

  • Overall Survival (OS) [ Time Frame: From randomization to end of study (Last subject last visit (LSLV)) (up to approximately 24 months) ]
    To assess the efficacy of AZD9291 compared with platinum-based doublet chemotherapy by assessment of Overall Survival (OS).

  • Tumour shrinkage according to RECIST 1.1 [ Time Frame: At baseline and every 6 weeks from randomization until progression (up to approximately 12 months) ]
    To assess the efficacy of AZD9291 compared with platinum-based doublet chemotherapy by assessment of Tumour shrinkage using investigator assessment according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1).

  • Patient Reported Outcomes by EORTC QLQ-C30 questionnaire [ Time Frame: Questionnaires completed at baseline and every 6 weeks from randomization until end of study (up to approximately 24 months) ]
    To assess the impact of AZD9291 compared with platinum-based doublet chemotherapy on patients' disease-related symptoms and health related quality of life (HRQoL)

  • Patient Reported Outcomes by EORTC QLQ-LC13 questionnaire [ Time Frame: Questionnaires completed at baseline and every 3 weeks from randomization until end of study (up to approximately 24 months) ]
    To assess the impact of AZD9291 compared with platinum-based doublet chemotherapy on patients' disease-related symptoms and health related quality of life (HRQoL)

  • Patient Reported Outcomes by EQ-5D-5L questionnaire [ Time Frame: Questionnaires completed at baseline and every 6 weeks from randomization until end of study (up to approximately 24 months) ]
    To assess the impact of AZD9291 compared with platinum-based doublet chemotherapy on patients' disease-related symptoms and health related quality of life (HRQoL)


Other Outcome Measures:
  • Safety and Tolerability as assessed by number and severity of adverse events, clinical chemistry, haematology, urinalysis, vital signs, physical examination, weight, ECG and WHO Performance status [ Time Frame: Adverse events will be collected from baseline until 28 days after the last dose, expected average 13 months ]
    To assess the safety and tolerability profile of AZD9291 compared with platinum-based doublet chemotherapy.


Enrollment: 1104
Study Start Date: August 2014
Estimated Study Completion Date: January 2018
Primary Completion Date: April 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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02151981

  Show 131 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
Study First Received: May 15, 2014
Last Updated: January 23, 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

ClinicalTrials.gov processed this record on May 25, 2017