A Study of Erlotinib in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This open-label, multi-center study will evaluate the progression-free survival and safety of erlotinib in participants with locally advanced or metastatic non-small cell lung cancer with activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR). Participants will receive daily oral doses of erlotinib until disease progression or unacceptable toxicity.

Official Title
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Phase IIIb, Open-Label Study of Erlotinib (Tarceva®) Treatment in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Present Activating Mutations in the Tyrosine Kinase Domain of the Epidermal Growth Factor Receptor

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of locally advanced or metastatic non-small cell lung cancer with activating mutations in the tyrosine kinase domain of the EGFR Measurable disease according to RECIST Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Life expectancy greater than or equal to (>/=) 12 weeks Adequate hematological, liver and renal function Participants with asymptomatic and stable cerebral metastases receiving medical treatment Exclusion Criteria: Previous chemotherapy or treatment against EGFR for metastatic disease Treatment with an investigational agent less than 3 weeks before enrollment History of neoplasm other than non-small cell lung cancer (except carcinoma in situ of the uterine cervix, basal cell skin carcinoma, or prostate carcinoma) Participants with symptomatic cerebral metastases Any significant ophthalmologic abnormality Unstable systemic disease Coumarins use Evidence of any other disease, neurological or metabolic dysfunction, physical examination or laboratory finding contraindicating the use of an investigational drug Participants with pre-existing parenchymal lung disease such as pulmonary fibrosis, lymphangiosis carcinomatosis Participants with known infection with human immunodeficiency virus (HIV), Hepatitis B (HBV), Hepatitis C (HCV)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erlotinib<br>Erlotinib will be administered as a single daily oral dose of 150 milligrams until disease progression, death or unacceptable toxicity. | Drug: Erlotinib<br>* Daily oral doses administered until disease progression or unacceptable toxicity or death.<br>* Other names: Tarceva;|
| No Intervention: Diagnostic Phase<br>Participants with advanced or metastatic NSCLC were tested for EGFR mutations. Participants who did not have an EGFR mutation were excluded from the study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v 1.1) | Kaplan Meier estimate of the median PFS was defined as the time at which half of the participants have progressed (progressive disease [PD]) based on RECIST tumor response criteria or died from any cause, whichever occurred first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Patients who had not died or progressed at the time of the final analysis were censored at the date of last contact. | Baseline until disease progression, or death, whichever occurs first (approximately up to 4 years and 9 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Objective Response as Assessed by RECIST v 1.1 | Objective response (OR) was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of complete response (CR) and partial response (PR) four at least 4 weeks during treatment. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. | Baseline until disease progression, or death, whichever occurs first (approximately up to 4 years and 9 months) | 
| Proportion of Participants With Disease Control as Assessed by RECIST v 1.1 | Disease control was defined as objective response or stable disease (SD) for at least 6 weeks. OR was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of CR and PR four at least 4 weeks during treatment. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. | Baseline until disease progression, or death, whichever occurs first (approximately up to 4 years and 9 months) | 
| Proportion of Participants With Epidermal Growth Factor Receptor (EGFR) Mutations | Mutations in the EGFR included exon 19 deletion mutations and the single-point substitution mutation L858R in exon 21. | Screening up to approximately 7 days | 
| Percentage of Participants With Adverse Events | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. | Baseline up to approximately 4 years and 9 months | 
| Change From Baseline to End of Study in Quality of Life Score Using The Functional Assessment of Cancer Therapy Lung (FACT-L) | The domains in the Quality of life score using the Functional Assessment of Cancer Therapy Lung (FACT-L) include physical, social/family, emotional, and functional well-being, and a lung cancer subscale include symptoms, cognitive function and regret of smoking. Minimum and maximum value of the scale is 0 and 4, respectively. Higher score indicate better health state. | Baseline and end of study (approximately 4 years and 9 months) |