Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.
 
ClinicalTrials.gov Identifier: NCT02094261
Recruitment Status : Active, not recruiting
First Posted : March 21, 2014
Results First Posted : June 7, 2016
Last Update Posted : February 23, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE March 17, 2014
First Posted Date  ICMJE March 21, 2014
Results First Submitted Date  ICMJE April 28, 2016
Results First Posted Date  ICMJE June 7, 2016
Last Update Posted Date February 23, 2021
Actual Study Start Date  ICMJE May 20, 2014
Actual Primary Completion Date May 1, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 11, 2016)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 20, 2014)
ORR according to RECIST 1.1 [ Time Frame: At baseline and every 6 weeks from time of first dose, participants will be followed by CT/MRI scans for RECIST 1.1 until date of progression, for an average of approximately 11 months ]
To assess the efficacy of AZD9291 by assessment of Objective Response Rate (ORR) by Independent Central Review.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 11, 2016)
  • 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).
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2014)
  • PFS according to RECIST 1.1 [ Time Frame: At baseline and every 6 weeks from time of first dose, participants will be followed by CT/MRI scans for RECIST 1.1 until date of progression, for an average of approximately 11 months ]
    To assess the efficacy of AZD9291 regarding Progression Free Survival (PFS).
  • Plasma concentrations of AZD9291 and active metabolites (AZ5104 and AZ7550) and PK parameters following dosing (Cmax, Css max, tmax, tss max, AUC 0-24, AUCss, Css min, CLss/F, RAC and ratio of metabolite to AZD9291) [ Time Frame: Blood samples will be collected from each participant at pre-specified times after the first dose on Cycle 1 Day 1 (pre-dose, 1, 2, 4, 6, 8 hours), Cycle 2 Day 1 (pre-dose), Cycle 3 Day 1 (pre-dose, 1, 2, 4, 6, 8, 10, 12, and 24 hours) ]
    To characterise the pharmacokinetics (PK) of AZD9291 and its metabolites (AZ5104 and AZ7550)
  • Patient Reported Outcomes by EORTC QLQ-C30 questionnaire [ Time Frame: Questionnaires completed at baseline, every 6 weeks (relative to first dose), discontinuation and every 6 weeks during the progression and survival follow-up periods for approximately 2 years. ]
    To assess the impact of AZD9291 on patients' disease-related symptoms and health related quality of life (HRQoL).
  • QTc interval by digital ECG [ Time Frame: From baseline to date of progression or treatment discontinuation, whichever comes first, assessed for approximately 11 months. ]
    To investigate the effects of AZD9291 on QTc interval after oral dosing to NSCLC patients.
  • Overall Survival (OS) [ Time Frame: From first dose to end of study or date of death from any cause, whichever comes first, assessed every 6 weeks up to approximately 60 months. ]
    To assess the efficacy of AZD9291 regarding overall survival.
  • DoR according to RECIST 1.1 [ Time Frame: At baseline and every 6 weeks from time of first dose, participants will be followed by CT/MRI scans for RECIST 1.1 until date of progression, for an average of approximately 11 months ]
    To assess the efficacy of AZD9291 regarding Duration of response (DoR)
  • DCR according to RECIST 1.1 [ Time Frame: At baseline and every 6 weeks from time of first dose, participants will be followed by CT/MRI scans for RECIST 1.1 until date of progression, for an average of approximately 11 months ]
    To assess the efficacy of AZD9291 regarding Disease Control Rate (DCR).
  • Tumour shrinkage according to RECIST 1.1 [ Time Frame: At baseline and every 6 weeks from time of first dose, participants will be followed by CT/MRI scans for RECIST 1.1 until date of progression, for an average of approximately 11 months ]
    To assess the efficacy of AZD9291 regarding tumour shrinkage.
  • Patient Reported Outcomes by EORTC QLQ LC13 questionnaire [ Time Frame: Questionnaires completed at baseline, weekly for the fist 3 weeks, then every 6 weeks (relative to first dose), discontinuation and every 6 weeks during the progression and survival follow-up periods for approximately 2 years. ]
    To assess the impact of AZD9291 on patients' disease-related symptoms and health related quality of life (HRQoL).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: March 20, 2014)
Safety and tolerability of AZD9291, as assessed by number and severity of adverse events as recorded on the case report form, 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
 
Descriptive Information
Brief Title  ICMJE Phase II AZD9291 Open Label Study in NSCLC After Previous EGFR TKI Therapy in EGFR and T790M Mutation Positive Tumours
Official Title  ICMJE 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
Brief Summary 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
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non Small Cell Lung Cancer
Intervention  ICMJE Drug: AZD9291
Once daily tablet 80 mg
Study Arms  ICMJE Experimental: AZD9291
Once daily tablet 80 mg
Intervention: Drug: AZD9291
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 26, 2017)
210
Original Estimated Enrollment  ICMJE
 (submitted: March 20, 2014)
442
Estimated Study Completion Date  ICMJE December 31, 2021
Actual Primary Completion Date May 1, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Hong Kong,   Italy,   Japan,   Korea, Republic of,   Spain,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02094261
Other Study ID Numbers  ICMJE D5160C00002
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
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
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
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Glenwood Goss, MD 501 Smyth Road, Ottawa, Canada
Principal Investigator: Tetsuya Mitsudomi, MD Kinki University Hospital, Faculty of Medicine, Osaka, Japan
PRS Account AstraZeneca
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP