A Study to Assess the Incidence of EGFR Mutation in Patients With Newly Diagnosed Locally Advanced or Metastatic Non-Small Cell Lung Cancer in the UK, And of Tarceva (Erlotinib) as First-Line Therapy in EGFR Mutation Positive Patients.

Study Overview
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Brief Summary
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This study will assess the prevalence of epidermal growth factor receptor (EGFR) mutations in newly diagnosed patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). Patients with positive EGFR mutation results will enter an open-label, single arm study to evaluate progression-free survival and quality of life with first-line Tarceva (erlotinib) therapy. Patients will receive Tarceva at a dose of 150 mg orally daily. Anticipated time on study treatment is until progressive disease or unacceptable toxicity occurs. Patients with negative EGFR mutation results will be offered treatment as per the centre's standard of care.

Official Title
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Assess the Incidence of Mutations in the Tyrosine Kinase Domain of the Endothelial Growth Factor Receptor in UK Patients With Newly Diagnosed Metastatic or Recurrent Non-small Cell Lung Cancer and to Investigate the Quality of Life of These Patients Undergoing First-line Therapy With Erlotinib.

Conditions
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Non-Squamous 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 Locally advanced or metastatic (stage IIIB/IV) non-small cell lung cancer (NSCLC) ECOG performance status 0-3 Treatment phase: histologically confirmed EGFR exon 19 deletion or exon 21 mutation in the diagnostic phase of the study Adequate haematological, liver and renal function Female patients must be postmenopausal, surgically sterile, or agree to use a barrier method of contraception Male patients must be surgically sterile or agree to use a barrier method of contraception Exclusion Criteria: Previous treatment for NSCLC with chemotherapy or therapy against EGFR, either with antibody or small molecule (tyrosine kinase inhibitor) Symptomatic cerebral metastases Pregnant or lactating women Any other concomitant anti-cancer therapy (until disease progression and discontinuation of Tarceva therapy)

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: Single Arm<br> | Drug: erlotinib [Tarceva]<br>* 150 mg daily, orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Tested Positive for EGFR Mutations | All participants newly diagnosed with recurrent or metastatic NSCLC were tested for EGFR exon 19 deletion or exon 21 mutations. | 14 days | 
| Percentage of Participants With EGFR Mutations by Subgroup | Incidence of EGFR mutations were summarized with respect to different subgroups as follows: (1) equals (=) Histopathology, (2) = Stage of disease, (3) = Age at consent, (4) = Gender, (5) = Race, (6) = Smoking history. | 14 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Response by Best Objective Tumor Response | Best objective response was defined as the best response recorded from the start of treatment until disease progression/recurrence. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). Partial Response (PR): At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. | Screening, Day 1 of each 6 week visit starting from Visit 3 until PD, Death, Unacceptable Toxicity or Withdrawal of Consent up to 34 months | 
| Probability of Being Alive and Free of Progression by Timepoint | Progression Free Survival (PFS) was defined as the interval (number of days) from the trial treatment start date to the earlier of the date of the first tumor response assessment of PD or the date of death by any cause. Participants who experienced neither of these events or who were lost to followup at the time of the analysis were censored at date of last contact. PFS was summarized according to the Kaplan-Meier method. | Months 0, 3, 6, 9, 12, 15, and 18 | 
| Survival Time in Months | Duration of time in months from Screening until Death due to any cause. | Baseline, Day 1 of each 6-week visit starting from Visit 3 until PD, Death, Unacceptable toxicity or Withdrawal of consent up to 34 months | 
| Quality of Life Assessment Using EuroQol(EQ) 5D Visual Analog Score (VAS) Instrument | The EQ-5D contains a descriptive system that measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The EQ-5D also contains a visual analog scale (EQ-VAS), which records the respondent's self-rated health status on a vertical graduated visual analog scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). A negative change indicates improvement. | Screening, Baseline and Final or Withdrawal Visit up to 34 months | 
| Percentage of Participants With Problems With Mobility as Assessed Using the EQ-5D | The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The participants were required to rate their mobility as the following categories: Category 1. I have no problems in walking about; Category 2. I have some problems in walking about; Category 3. I am confined to bed. | Baseline (Visit 1), Days 10 to 14 (Visit 2), Day 1 of every 6 weeks until PD, Death, Unacceptable toxicity or Withdrawal of consent up to 34 months | 
| Percentage of Participants With Problems With Self-Care as Assessed Using the EQ-5D | The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The participants were required to rate their self-care as the following categories: Category 1. I have no problems with self-care; Category 2. I have some problems washing or dressing myself; Category 3. I am unable to wash or dress myself. | Baseline (Visit 1), Days 10 to 14 (Visit 2), Day 1 of every 6 weeks until PD, Death, Unacceptable toxicity or Withdrawal of consent up to 34 months | 
| Percentage of Participants With Problems With Usual Activities as Assessed Using the EQ-5D | The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The participants were required to rate their ability to perform usual activities as the following categories: Category 1. I have no problems with performing my usual activities; Category 2. I have some problems with performing my usual activities; Category 3. I am unable to perform my usual activities. | Baseline (Visit 1), Days 10 to 14 (Visit 2), Day 1 of every 6 weeks until PD, Death, Unacceptable toxicity or Withdrawal of consent up to 34 months | 
| Percentage of Participants With Pain/Discomfort as Assessed Using the EQ-5D | The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The participants were required to rate their pain as the following categories: Category 1. I have no pain or discomfort; Category 2. I have moderate pain or discomfort; Category 3. I have extreme pain or discomfort. | Baseline (Visit 1), Days 10 to 14 (Visit 2), Day 1 of every 6 weeks until PD, Death, Unacceptable toxicity or Withdrawal of consent up to 34 months | 
| Percentage of Participants With Anxiety/Depression as Assessed Using the EQ-5D | The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The participants were required to rate their pain as the following categories: Category 1. I am not anxious or depressed; Category 2. I am moderately anxious or depressed; Category 3.I am extremely anxious or depressed. | Baseline (Visit 1), Days 10 to 14 (Visit 2), Day 1 of every 6 weeks until PD, Death, Unacceptable toxicity or Withdrawal of consent up to 34 months |