A Study of Erlotinib (Tarceva) in Participants With Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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This study will assess potentially predictive markers of efficacy in participants with NSCLC receiving oral erlotinib (Tarceva) therapy. The anticipated time on study treatment is until disease progression, unacceptable toxicity or death.

Official Title
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MERIT - A Phase II Marker Identification Trial for Tarceva in Second Line NSCLC Patients

Conditions
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Non-Squamous 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: Advanced NSCLC Tumor accessible for biopsy by bronchoscopy Disease progression following course of standard chemotherapy, or participants unwilling/unable to undergo chemotherapy Exclusion Criteria: Unstable systemic disease Any other malignancies in the last 5 years Brain metastases Previous treatment with therapy acting on the epidermal growth factor receptor (EGFR) axis

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erlotinib<br>Participants will receive erlotinib orally daily until disease progression, unacceptable toxicity or death. | Drug: Erlotinib<br>* Erlotinib will be administered at 150 milligrams (mg) orally daily until disease progression, unacceptable toxicity or death.<br>* Other names: Tarceva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Differentially Expressed Genes Associated With Clinical Benefit | Affymetrix gene expression profiles were primarily analyzed to identify differentially expressed genes between the participants who derived clinical benefit status and those who did not. Analysis was performed using a multivariate linear model (with clinical benefit status, histology, ethnicity, sex, RNA integrity number (RIN), smoking status and stage as predictors), and a False Discovery Rate criteria of below 0.3 as cut-off. Clinical benefit is defined in the Outcome Measure 5. | Baseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years | 
| Number of Epidermal Growth Factor Receptor (EGFR) Mutation Participants Who Achieved Clinical Benefit | Affymetrix gene expression profiles were primarily analyzed to identify differentially expressed genes between the participants who derived clinical benefit status and those who did not. Analysis was performed using a multivariate linear model (with clinical benefit status, histology, ethnicity, sex, RNA integrity number (RIN), smoking status and stage as predictors), and a False Discovery Rate criteria of below 0.3 as cut-off. Number of participants with EGFR mutation (L858R/ exon 19 deletion) and who achieved clinical benefit status was reported. Clinical benefit is defined in the Outcome Measure 5. | Baseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years | 
| Number of KRAS Mutation Participants Who Achieved Clinical Benefit | Affymetrix gene expression profiles were primarily analyzed to identify differentially expressed genes between the participants who derived clinical benefit status and those who did not. Analysis was performed using a multivariate linear model (with clinical benefit status, histology, ethnicity, sex, RNA integrity number (RIN), smoking status and stage as predictors), and a False Discovery Rate criteria of below 0.3 as cut-off. Number of participants with KRAS gene mutation and who achieved clinical benefit status was reported. Clinical benefit is defined in the Outcome Measure 5. | Baseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Overall Response of Complete Response (CR) or Partial Response (PR) Using Response Evaluation Criteria in Solid Tumors (RECIST) | Tumor response was defined as either a CR or a PR prior to failure (disease progression, death from any cause, or a second malignancy). CR was defined as the complete disappearance on magnetic response imaging of all enhancing tumor and mass effect on a stable or decreasing dose of dexamethasone (or only receiving adrenal replacement doses) accompanied by a stable or improving neurologic examination that was maintained for at least 12 weeks. PR was defined as a greater than or equal to 50 percent (%) reduction in tumor size by bi-dimensional measurement on a stable or decreasing dose of dexamethasone accompanied by a stable or improving neurologic examination that was maintained for at least 12 weeks. | Baseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years | 
| Percentage of Participants With Clinical Benefit (CR, PR, or Stable Disease [SD] for at Least 12 Weeks After Study Entry) Using RECIST | Clinical benefit was defined as either a CR, PR, or SD prior to failure (disease progression, death from any cause, or a second malignancy). CR: complete disappearance on magnetic response imaging of all enhancing tumor and mass effect on a stable or decreasing dose of dexamethasone (or only receiving adrenal replacement doses) accompanied by a stable or improving neurologic examination that was maintained for at least 12 weeks. PR: greater than or equal to 50% reduction in tumor size by bi-dimensional measurement on a stable or decreasing dose of dexamethasone accompanied by a stable or improving neurologic examination that was maintained for at least 12 weeks. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) taking as reference smallest sum of longest dimensions since treatment started associated to non-progressive disease response for non-target lesions. PD: unequivocal progression of existing non-target lesions. | Baseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years |