A Study of Tarceva (Erlotinib) in Patients With Advanced Non-Small Cell Lung Cancer Naive to Chemotherapy

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of Tarceva in two groups of patients with non-small cell lung cancer who have not been pre-treated with chemotherapy. One group, consisting of patients who have never smoked, will receive Tarceva 150 mg/day, and the other group, consisting of current/former smokers, will receive Tarceva 150 mg/day increasing to a maximum of 300 mg/day. The anticipated time on study treatment is 1-2 years.

Official Title
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An Parallel Phase II Study of Tarceva (Erlotinib) in Patients With Advanced Non-small Cell Lung Cancer (Stage IIIB/IV) Not Pre-treated by Chemotherapy Including Dose Escalation to Toxicity in Current and Former Smokers

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: erlotinib [Tarceva]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >=18 years of age; histologically documented advanced non-small cell lung cancer (stage IIIB/IV); Eastern Cooperative Oncology Group (ECOG) performance status 0-2; no previous chemotherapy. Exclusion Criteria: previous therapy which acts on Epidermal Growth Factor Receptor (EGFR) axis; clinical evidence of brain metastasis; any unstable systemic disease; unable to take oral medication; any significant ophthalmological abnormality.

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Never Smokers<br>Never Smokers (participants who smoked ≤ 100 cigarettes in entire lifetime or had never smoked cigarettes) received erlotinib [Tarceva] 150 mg orally daily until disease progression or unacceptable toxicity. | Drug: erlotinib [Tarceva]<br>* Erlotinib tablets taken orally once daily in the morning.<br>* Other names: Tarceva;|
| Experimental: Current/Former Smokers<br>Current Smokers (participants who smoked > 100 cigarettes in entire lifetime and either quit smoking < 1 year ago or were currently smoking) or Former Smokers (participants who smoked > 100 cigarettes in entire lifetime and quit smoking ≥ 1 year ago) received erlotinib [Tarceva] 150 mg orally daily, increasing to a maximum of 300 mg orally daily until disease progression or unacceptable toxicity. | Drug: erlotinib [Tarceva]<br>* Erlotinib tablets taken orally once daily in the morning.<br>* Other names: Tarceva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-Progression Rate (NPR) at 8 Weeks | Non-Progressive Rate (NPR) was defined as the percentage of participants without progression (had stable disease (SD) or better) based on (Response Evaluation Criteria in Solid Tumours (RECIST) criteria 8 weeks after start of treatment. Diagnosis of Progressive Disease (PD) was made by objective criteria (RECIST criteria) on the target lesion(s), or by documenting, with Computerised Tomography/Magnetic Resonance Imaging (CT/MRI) scans, the presence of newly occurring lesion(s) arising outside the scanned areas of the target lesions. PD required at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Objective response rate was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) by Response Evaluation Criteria in Solid Tumours (RECIST). The best overall response was the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). The patient's best response assignment depended on the achievement of both measurement and confirmation criteria. To be assigned the status of PR or CR, changes in tumour measurements were to be confirmed by repeated assessments no less than 4 weeks after the criteria for response were first met. CR was defined as the disappearance of all target lesions; for non-target lesions disappearance of lesions and normal tumour marker levels. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, using as reference the Baseline sum LD. | Up to 2 years | 
| Disease Control Rate | Disease Control Rate was defined as the percentage of participants with Complete Response (CR), Partial Response (PR) or Stable Disease (SD) by Response Evaluation Criteria in Solid Tumours (RECIST). CR was defined as the disappearance of all target lesions; for non-target lesions disappearance of lesions and normal tumour marker levels. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, using as reference the Baseline sum LD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started; for non-target lesions persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits. | Up to 2 years | 
| Duration of Response | Duration of overall response was defined as the time in months from Complete Response (CR) or Partial Response (PR) by Response Evaluation Criteria in Solid Tumours (RECIST) until the first date Progressive Disease (PD) was objectively documented (taking as reference for PD the smallest measurements recorded since the treatment started) or until the date of death. CR was defined as the disappearance of all target lesions; for non-target lesions disappearance of lesions and normal tumour marker levels.PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, using as reference the Baseline sum LD. PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Up to 2 years | 
| Time to Progression | Time to progression was defined as the time from start of treatment until the first date criteria for Progressive Disease (PD) was met (taking as reference the smallest measurements recorded since the treatment started). Diagnosis of PD was made by objective criteria (RECIST criteria) on the target lesion(s), or by documenting, with Computerised Tomography/Magnetic Resonance Imaging (CT/MRI) scans, the presence of newly occurring lesion(s) arising outside the scanned areas of the target lesions. PD required at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Up to 2 years | 
| Progression-Free Survival | Progression-Free Survival (PFS) was defined as the time in months from the start of treatment until the first date criteria for Progressive Disease (PD) were met (taking as reference the smallest measurements recorded since the treatment started), or the date of death for any reason in the absence of PD. Diagnosis of PD was made by objective criteria (RECIST criteria) on the target lesion(s), or by documenting, with Computerised Tomography/Magnetic Resonance Imaging (CT/MRI) scans, the presence of newly occurring lesion(s) arising outside the scanned areas of the target lesions. | Up to 2 years | 
| Overall Survival | Overall survival was defined as the time in months from the start of treatment to the date of death irrespective of the cause of death. | Up to 2 years | 
| Safety: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant. | Up to 2 years |