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AZD9291 Versus Gefitinib or Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (FLAURA)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02296125
First received: October 22, 2014
Last updated: March 20, 2017
Last verified: March 2017
October 22, 2014
March 20, 2017
December 3, 2014
May 22, 2017   (Final data collection date for primary outcome measure)
Progression Free Survival (PFS) [ Time Frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression (approximately 11.5 months) ]
Defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression.
Progression Free Survival (PFS) [ Time Frame: At baseline and every 6 weeks until objective disease progression (approximately 11.5 months) ]
Defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression.
Complete list of historical versions of study NCT02296125 on ClinicalTrials.gov Archive Site
  • Objective Response Rate (ORR) [ Time Frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression (approximately 11.5 months) ]
    Defined as the number (%) of patients with measurable disease with at least 1 visit response of CR (Complete response) or PR (Partial response).
  • Progression Free Survival (PFS) in patients with positive (or negative) T790M mutation [ Time Frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression (approximately 11.5 months) ]
    PFS defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression.
  • 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 (approximately 29 months) ]
    Defined as the time from randomization until death from any cause
  • Patient Reported Outcome by Therapy Satisfaction (CTSQ-16 Questionnaire) [ Time Frame: Questionnaire completed in cycle 2 and 3, prior to Week 6 scan (approximately 2 months) ]
    Measured by the Cancer Therapy Satisfaction Questionnaire 16 items (CTSQ-16). The questionnaire assesses the satisfaction with and preference for chemo, hormonal, and biological therapies in either oral (pill) and/or IV form.
  • Plasma concentrations of AZD9291 and metabolites AZ5104 and AZ7550; and ratio of metabolite to AZD9291 [ Time Frame: Blood samples will be collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months) ]
    The pharmacokinetics exposure parameters derived from plasma concentrations of AZD9291 and metabolites AZ5104 and AZ7550.
  • Patients reported disease-related symptoms and HRQoL by EORTC QLQ-C30 [ Time Frame: Questionnaires completed at baseline and every 6 weeks until the time of second progression (approximately 20 months) ]
    Questionnaire consisting of 30 items measuring subjects general cancer symptoms and functioning.
  • Duration of Response (DoR) [ Time Frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression (approximately 11.5 months) ]
    Defined as the time from the date of first documented response (i.e., subsequently confirmed) until the date of documented progression or death in the absence of disease progression.
  • Disease Control Rate (DCR) [ Time Frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression (approximately 11.5 months) ]
    Defined as the percentage of patients who have a best overall response of CR or PR or SD (Stable disease).
  • Depth of response [ Time Frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression (approximately 11.5 months) ]
    Defined as the relative change in the sum of the longest diameters of RECIST target lesions at the nadir in the absence of new lesions or progression of non-target lesions compared to baseline.
  • Patients reported disease-related symptoms and HRQoL by EORTC QLQ-LC13 [ Time Frame: Questionnaires completed at baseline, weekly and then every 3 weeks until the time of second progression (approximately 20 months) ]
    A complementary questionnaire measuring lung cancer symptoms and side effects from conventional chemo- and radiotherapy.
  • Objective Response Rate (ORR) [ Time Frame: At baseline and every 6 weeks until objective disease progression (approximately 11.5 months) ]
    Defined as the number (%) of patients with measurable disease with at least 1 visit response of CR (Complete response) or PR (Partial response).
  • Progression Free Survival (PFS) in patients with positive (or negative) T790M mutation [ Time Frame: At baseline and every 6 weeks until objective disease progression (approximately 11.5 months) ]
    PFS defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression.
  • 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 (approximately 29 months) ]
    Defined as the time from randomization until death from any cause
  • Patient Reported Outcome by Therapy Satisfaction (CTSQ-16 Questionnaire) [ Time Frame: Questionnaire completed in cycle 2 and 3, prior to Week 6 scan (approximately 2 months) ]
    Measured by the Cancer Therapy Satisfaction Questionnaire 16 items (CTSQ-16). The questionnaire assesses the satisfaction with and preference for chemo, hormonal, and biological therapies in either oral (pill) and/or IV form.
  • Plasma concentrations of AZD9291 and metabolites AZ5104 and AZ7550; and ratio of metabolite to AZD9291 [ Time Frame: Blood samples will be collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months) ]
    The pharmacokinetics exposure parameters derived from plasma concentrations of AZD9291 and metabolites AZ5104 and AZ7550.
  • Patients reported disease-related symptoms and HRQoL by EORTC QLQ-C30 [ Time Frame: Questionnaires completed at baseline and every 6 weeks until the time of second progression (approximately 20 months) ]
    Questionnaire consisting of 30 items measuring subjects general cancer symptoms and functioning.
  • Duration of Response (DoR) [ Time Frame: At baseline and every 6 weeks until objective disease progression (approximately 11.5 months) ]
    Defined as the time from the date of first documented response (i.e., subsequently confirmed) until the date of documented progression or death in the absence of disease progression.
  • Disease Control Rate (DCR) [ Time Frame: At baseline and every 6 weeks until objective disease progression (approximately 11.5 months) ]
    Defined as the percentage of patients who have a best overall response of CR or PR or SD (Stable disease).
  • Depth of response [ Time Frame: At baseline and every 6 weeks until objective disease progression (approximately 11.5 months) ]
    Defined as the relative change in the sum of the longest diameters of RECIST target lesions at the nadir in the absence of new lesions or progression of non-target lesions compared to baseline.
  • Patients reported disease-related symptoms and HRQoL by EORTC QLQ-LC13 [ Time Frame: Questionnaires completed at baseline, weekly and then every 3 weeks until the time of second progression (approximately 20 months) ]
    A complementary questionnaire measuring lung cancer symptoms and side effects from conventional chemo- and radiotherapy.
Incidence of Adverse Events (AEs) [ Time Frame: Adverse events will be collected from baseline until 28 days after the last dose of AZD9291/SoC EGFR-TKI (expected average 13 months) ]
AEs graded by CTCAE version 4.0
Same as current
 
AZD9291 Versus Gefitinib or Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer
A Phase III, Double-blind, Randomised Study to Assess the Safety and Efficacy of AZD9291 Versus a Standard of Care Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor as First Line Treatment in Patients With Epidermal Growth Factor Receptor Mutation Positive, Locally Advanced or Metastatic Non Small Cell Lung Cancer.
To assess the efficacy and safety of AZD9291 versus a standard of care epidermal growth factor receptor tyrosine kinase inhibitor in patients with locally advanced or Metastatic Non Small Cell Lung Cancer
This is a Phase III, double-blind, randomised study assessing the efficacy and safety of AZD9291 (80 mg orally, once daily) versus a standard of care (SoC) Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) (either gefitinib [250 mg orally, once daily] or erlotinib [150 mg orally, once daily]) in patients with locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) that is known to be EGFR sensitising mutation (EGFRm) positive, treatment-naïve and eligible for first-line treatment with an EGFR-TKI.
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Locally Advanced or Metastatic EGFR Sensitising Mutation Positive Non Small Cell Lung Cancer
  • Drug: AZD9291 80 mg/40 mg + placebo

    The initial dose of AZD9291 80 mg once daily can be reduced to 40 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment.

    Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.

  • Drug: Placebo Erlotinib 150/100mg
    The initial dose of Placebo Erlotinib 150 mg once daily can be reduced to Placebo 100 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
    Other Name: Placebo Tarceva 150/100 mg
  • Drug: Placebo Gefitinib 250 mg
    The initial dose of Placebo Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
    Other Name: Placebo Iressa 250 mg
  • Drug: Erlotinib 150/100 mg

    The initial dose of Erlotinib 150mg once daily can be reduced to 10 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment.

    Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.

    Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291).

    Other Name: Tarceva 150/100 mg
  • Drug: Gefitinib 250 mg

    The initial dose of Gefitinib 250mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment.

    Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.

    Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291).

    Other Name: Iressa 250mg
  • Drug: Placebo AZD9291 80 mg/ 40 mg
    The initial dose of Placebo AZD9291 80 mg once daily can be reduced to Placebo AZD9291 40 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
  • Experimental: AZD9291 + placebo Standard of Care
    AZD9291 (80 mg or 40 mg orally, once daily) plus placebo Erlotinib (150 mg or 100 mg orally, once daily) or placebo Gefitinib (250 mg orally, once daily), in accordance with the randomisation schedule.
    Interventions:
    • Drug: AZD9291 80 mg/40 mg + placebo
    • Drug: Placebo Erlotinib 150/100mg
    • Drug: Placebo Gefitinib 250 mg
  • Active Comparator: Standard of Care + placebo AZD9291

    Erlotinib (150 mg or 100 mg orally, once daily) or placebo Gefitinib (250 mg orally, once daily) plus placebo AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomisation schedule.

    Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291).

    Interventions:
    • Drug: Erlotinib 150/100 mg
    • Drug: Gefitinib 250 mg
    • Drug: Placebo AZD9291 80 mg/ 40 mg
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
530
October 15, 2018
May 22, 2017   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Male or female, aged at least 18 years.
  2. Pathologically confirmed adenocarcinoma of the lung.
  3. Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy.
  4. The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R).
  5. Mandatory provision of an unstained, archived tumour tissue sample in a quantity sufficient to allow for central analysis of EGFR mutation status.
  6. Patients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with gefitinib or erlotinib as selected by the participating centre. Prior adjuvant and neo-adjuvant therapy is permitted(chemotherapy, radiotherapy, investigational agents).

Exclusion Criteria:

  1. Treatment with any of the following:

    • Prior treatment with any systemic anti-cancer therapy for locally advanced/metastatic NSCLC.
    • Prior treatment with an EGFR-TKI.
    • Major surgery within 4 weeks of the first dose of study drug.
    • Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.
    • Patients currently receiving medications or herbal supplements known to be potent inducers of cytochrome P450 (CYP) 3A4.
    • Alternative anti-cancer treatment
    • Treatment with an investigational drug within five half-lives of the compound or any of its related material.
  2. Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of study drug.
  3. Spinal cord compression, symptomatic and unstable brain metastases, except for those patients who have completed definitive therapy, are not on steroids, have a stable neurologic status for at least 2 weeks after completion of the definitive therapy and steroids.
  4. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
  5. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9291.
  6. Any of the following cardiac criteria:

    • Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTcF value.
    • Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
    • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval.
  7. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
Sexes Eligible for Study: All
18 Years to 100 Years   (Adult, Senior)
Yes
Contact information is only displayed when the study is recruiting subjects
Australia,   Belgium,   Brazil,   Bulgaria,   Canada,   China,   Czech Republic,   France,   Germany,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Malaysia,   Philippines,   Poland,   Portugal,   Romania,   Russian Federation,   Saudi Arabia,   Spain,   Sweden,   Switzerland,   Taiwan,   Thailand,   Turkey,   Ukraine,   United Kingdom,   United States,   Vietnam
 
 
NCT02296125
D5160C00007
2014-002694-11 ( EudraCT Number )
U1111-1160-2242 ( Other Grant/Funding Number: 112455 )
Yes
Not Provided
Not Provided
Not Provided
AstraZeneca
AstraZeneca
Parexel
Not Provided
AstraZeneca
March 2017

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