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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 29 January 2024
Main ID:  NCT02296125
Date of registration: 22/10/2014
Prospective Registration: Yes
Primary sponsor: AstraZeneca
Public title: AZD9291 Versus Gefitinib or Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer FLAURA
Scientific title: 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.
Date of first enrolment: December 3, 2014
Target sample size: 674
Recruitment status: Active, not recruiting
URL:  https://clinicaltrials.gov/ct2/show/NCT02296125
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).  
Phase:  Phase 3
Countries of recruitment
Australia Belgium Brazil Bulgaria Canada China Czech Republic Czechia
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
Contacts
Key inclusion & exclusion criteria

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).

7. Provision of informed consent prior to any study specific procedures, sampling, and
analysis.

8. World Health Organization Performance Status of 0 to 1 with no clinically significant
deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks

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 patient with 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.

8. Involvement in the planning and/or conduct of the study



Age minimum: 18 Years
Age maximum: 100 Years
Gender: All
Health Condition(s) or Problem(s) studied
Locally Advanced or Metastatic EGFR Sensitising Mutation Positive Non Small Cell Lung Cancer
Intervention(s)
Drug: Gefitinib 250 mg
Drug: Placebo AZD9291 80 mg/ 40 mg
Drug: AZD9291 80 mg/40 mg + placebo
Drug: Placebo Gefitinib 250 mg
Drug: Erlotinib 150/100 mg
Drug: Placebo Erlotinib 150/100mg
Primary Outcome(s)
Median Progression Free Survival (PFS) (Months) [Time Frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression]
Percentage of Participants in Progression Free Survival at 6, 12, and 18 Months [Time Frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression]
Secondary Outcome(s)
Plasma Concentrations of AZD9291 [Time Frame: Blood samples 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)]
Plasma Concentrations of Metabolites AZ5104 [Time Frame: Blood samples 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)]
Overall Survival (OS)- Number of Participants With an Event [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)]
Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) [Time Frame: Questionnaires completed at baseline, first 9 months, and at week 6, 12, 18, 24, 30, and 36.]
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]
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]
Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) [Time Frame: Questionnaire completed in cycle 2 and 3, prior to Week 6 scan (approximately 2 months)]
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) [Time Frame: Questionnaires completed at baseline, first 9 months, and at week 1, 2, 3, 4, 5, 6, 12, 18, 24, 30 and 36]
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]
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]
Plasma Concentrations of Metabolite AZ7550 [Time Frame: Blood samples 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)]
Secondary ID(s)
D5160C00007
U1111-1160-2242
2014-002694-11
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Parexel
Ethics review
Results
Results available: Yes
Date Posted: 06/11/2018
Date Completed:
URL: https://clinicaltrials.gov/ct2/show/results/NCT02296125
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