Efficacy, Safety, Tolerability of Gefitinib as 1st Line in Caucasian Patients With EGFR Mutation Positive Advanced NSCLC (IFUM)

An Open Label, Multicentre, Single Arm Study to Characterise the Efficacy, Safety and Tolerability of Gefitinib 250 mg (IRESSA™) as First Line Treatment in Caucasian Patients, Who Have Epidermal Growth Factor Receptor (EGFR) Mutation Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer

This study is carried out to see how Caucasian patients with lung cancer which has EGFR mutation will respond to gefitinib (IRESSA™) as a first line treatment. Safety data will also be collected and analysed to confirm that treatment with gefitinib is safe and well tolerated.

Study Overview

• Status: Completed
• Conditions: Caucasian Patients With EGFR Mutation Positive Advanced NSCLC
• Intervention / Treatment: Drug: Gefitinib

Detailed Description

An Open Label, Multicentre, Single Arm Study to Characterise the Efficacy, Safety and Tolerability of Gefitinib 250 mg (IRESSA™) as First line Treatment in Caucasian Patients, who have Epidermal Growth Factor Receptor (EGFR) Mutation Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer

• Study Type: Interventional
• Enrollment (Actual): 1060
• Phase: Phase 4

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria
    • Research Site
  • Sofia, Bulgaria
    • Research Site
  • Stara Zagora, Bulgaria
    • Research Site
  • Varna, Bulgaria
    • Research Site
  • Vratza, Bulgaria
    • Research Site
• France
  • ANGERS Cedex 9, France
    • Research Site
  • Saint Herblain Cedex, France
    • Research Site
• Greece
  • Athens, Greece
    • Research Site
  • Heraklion, Greece
    • Research Site
  • Larissa, Greece
    • Research Site
  • Thessaloniki, Greece
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• Hungary
  • Budapest, Hungary
    • Research Site
  • Deszk, Hungary
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  • Edelény, Hungary
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  • Győr, Hungary
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  • Mosdós, Hungary
    • Research Site
  • Székesfehérvár, Hungary
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• Italy
  • Ancona, Italy
    • Research Site
  • Carpi, Italy
    • Research Site
  • Livorno, Italy
    • Research Site
  • Perugia, Italy
    • Research Site
• Norway
  • Oslo, Norway
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  • Stavanger, Norway
    • Research Site
  • Trondheim, Norway
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• Poland
  • Gdańsk, Poland
    • Research Site
  • Kraków, Poland
    • Research Site
  • Lubin, Poland
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  • Olsztyn, Poland
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  • Otwock, Poland
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  • Szczecin, Poland
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  • Toruń, Poland
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  • Warszawa, Poland
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  • Wrocław, Poland
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• Portugal
  • Coimbra, Portugal
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  • Lisboa, Portugal
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  • Porto, Portugal
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  • Vila Nova de Gaia, Portugal
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• Romania
  • Brasov, Romania
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  • Bucharest, Romania
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  • Bucuresti, Romania
    • Research Site
  • Cluj Napoca, Romania
    • Research Site
  • Constanta, Romania
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• Spain
  • Lugo, Spain
    • Research Site
  • Lérida, Spain
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  • Madrid, Spain
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  • Majadahonda, Spain
    • Research Site
  • Málaga, Spain
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• Switzerland
  • Basel, Switzerland
    • Research Site
  • Chur, Switzerland
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  • Rapperswil-Jona, Switzerland
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  • Sursee, Switzerland
    • Research Site
• Turkey
  • Ankara, Turkey
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  • Istanbul, Turkey
    • Research Site
  • Izmir, Turkey
    • Research Site
• United Kingdom
  • Aberdeen, United Kingdom
    • Research Site
  • Birmingham, United Kingdom
    • Research Site
  • Burnley, United Kingdom
    • Research Site
  • Cambridge, United Kingdom
    • Research Site
  • Dundee, United Kingdom
    • Research Site
  • Liverpool, United Kingdom
    • Research Site
  • Nottingham, United Kingdom
    • Research Site
  • Wolverhampton, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Locally advanced or metastatic non-small cell lung cancer (i.e. cancer that has spread from where it started) which is EGFR mutation positive
• Caucasian female or male patients aged 18 years or over
• Measurable disease, i.e. at least one lesion, not previously irradiated, as ≥ 10 mm in the longest diameter (≥ 15 mm in short axis for lymph node )

Exclusion Criteria:

• Prior adjuvant chemotherapy or other systemic anti-cancer treatment less than 6 month, or palliative radiotherapy less than 4 weeks prior to start of study treatment.
• Brain metastases or spinal cord compression, unless treated and stable without steroids
• Any clinically significant illness, which will jeopardize the patients' safety and their participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 1; gefitinib 250mg tablet	Drug: Gefitinib; 250mg tablet oral, once daily until objective disease progression is documented or until other discontinuation criterion is met; Other Names: IRESSA™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) (Investigator)	% of patients in the Full analysis set who have a complete response [CR] or partial response [PR] confirmed by repeat imaging at least 4 weeks later with no evidence of progression between confirmation visits (as defined by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1)). CR: disappearance of all target lesions (TLs) & non-target lesions (NTLs). PR: >= 30% decrease in the sum of diameters compared to baseline (with no evidence of progression) and the NTLs are at least stable with no evidence of new lesions. Outcome is based on measurements made at site by investigator.	Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR) (Investigator)	DCR is calculated as the % of the FAS patient population with a best visit response of CR, PR (a visit response of CR or PR which is confirmed at least 4 weeks later) or stable disease (SD). SD is defined as no evidence of CR, PR or progression and must have occurred at a minimum of 6 weeks after first dose of study treatment. (progression is defined as ≥20% increase in the sum of the diameters of target lesions from minimum; clinically significant progression in non-target lesions; the presence of a new lesion or death). Outcome is based on measurements made at site by investigator.	Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months
Progression - Free Survival (PFS) (Investigator)	PFS was defined as the time from the first dose of gefitinib study treatment until objective disease progression as defined by RECIST 1.1 (≥20% increase in the sum of the diameters of target lesions from minimum, clinically significant progression in non-target lesions or the presence of a new lesion) or death (by any cause in the absence of progression). Progression is based on measurements made at site by investigator.	Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months
Overall Survival (OS)	OS was defined as the time from first dose of gefitinib study treatment until death by any cause. Patients who had not died at the time of analysis were censored at the last date the patient was known to be alive.	Survival follow up from first dose of gefitinib till death of the patient or till end of study in absence of death.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR) (Independent Central Review)	DCR is calculated as the % of the FAS patient population with a best visit response of CR, PR (a visit response of CR or PR which is confirmed at least 4 weeks later) or stable disease (SD). SD is defined as no evidence of CR, PR or progression and must have occurred at a minimum of 6 weeks after first dose of study treatment. (progression is defined as ≥20% increase in the sum of the diameters of target lesions from minimum; clinically significant progression in non-target lesions; the presence of a new lesion or death). Outcome is based on measurements of scans by central review.	Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months
Objective Response Rate (ORR) (Independent Central Review))	% of patients in the Full analysis set who have a complete response [CR] or partial response [PR] confirmed by repeat imaging at least 4 weeks later with no evidence of progression between confirmation visits (as defined by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1)). CR: disappearance of all target lesions (TLs) & non-target lesions (NTLs). PR: >= 30% decrease in the sum of diameters compared to baseline (with no evidence of progression) and the NTLs are at least stable with no evidence of new lesions. Outcome is based on measurements of scans by central review.	Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months
Progression - Free Survival (PFS) (Independent Central Review)	PFS was defined as the time from the first dose of gefitinib study treatment until objective disease progression as defined by RECIST 1.1 (≥20% increase in the sum of the diameters of target lesions from minimum, clinically significant progression in non-target lesions or the presence of a new lesion) or death (by any cause in the absence of progression). Progression is based on measurements of scans by central review.	Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Haiyi Jiang, AstraZeneca

Publications and helpful links

General Publications

• Douillard JY, Ostoros G, Cobo M, Ciuleanu T, McCormack R, Webster A, Milenkova T. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer. 2014 Jan 7;110(1):55-62. doi: 10.1038/bjc.2013.721. Epub 2013 Nov 21.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: September 7, 2010
• First Submitted That Met QC Criteria: September 15, 2010
• First Posted (Estimate): September 17, 2010

Study Record Updates

• Last Update Posted (Estimate): January 2, 2017
• Last Update Submitted That Met QC Criteria: November 14, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: safety; efficacy; Gefitinib; EGFR TKI; Caucasian patients; EGFR mutation positive advanced NSCLC
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Gefitinib
• Other Study ID Numbers: D791AC00014