A Study for Non-Smoker Patients With Nonsquamous Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of this study is to compare the combination of erlotinib and pemetrexed versus either pemetrexed alone and erlotinib alone, in terms of progression-free survival (time until the objective worsening of the disease) in patients who have never smoked and have locally advanced or metastatic Nonsquamous Non-Small Cell Lung Cancer who have failed a first-line chemotherapy treatment.

Official Title
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A Randomized Phase 2 Study Comparing Erlotinib-Pemetrexed, Pemetrexed Alone, and Erlotinib Alone, as Second-Line Treatment for Non-Smoker Patients With Locally Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer

Conditions
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Non-Small-Cell Lung Cancer

Intervention / Treatment
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* Drug: pemetrexed
* Drug: erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with locally advanced or metastatic nonsquamous non-small cell lung cancer Patients must be non-smokers Patients must have at least one measurable lesion Performance status of 0 to 2 on the Eastern Cooperative Oncology Group Scale Patients must have failed only one prior chemotherapy regimen and must be considered eligible for further chemotherapy following progression of their disease. Exclusion Criteria: Patients who have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication Patients who have previously received treatment with drugs against the human epidermal growth factor receptors Patients who have previously received treatment with drugs which have similar targets as Pemetrexed Patients who have any known significant ophthalmologic abnormalities of the surface of the eye Patients who have a history of severe hypersensitivity reaction to erlotinib or pemetrexed

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pemetrexed + Erlotinib<br>Pemetrexed 500 milligrams per meter squared (mg/m^2) of body surface area, administered by intravenous (IV) infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months. | Drug: pemetrexed<br>* 500 milligrams per meter squared (mg/m^2), intravenous (IV), every (q) 21 days until progression or unacceptable toxicity develops<br>* Other names: Alimta;Drug: erlotinib<br>* 150 mg, orally, once daily until progression or unacceptable toxicity develops<br>|
| Active Comparator: Erlotinib<br>Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months. | Drug: erlotinib<br>* 150 mg, orally, once daily until progression or unacceptable toxicity develops<br>|
| Active Comparator: Pemetrexed<br>Pemetrexed 500 mg/m^2 of body surface area, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months. | Drug: pemetrexed<br>* 500 milligrams per meter squared (mg/m^2), intravenous (IV), every (q) 21 days until progression or unacceptable toxicity develops<br>* Other names: Alimta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS is defined as the time from randomization to the first date of progressive disease (PD; either objectively determined or clinical progression) or death from any cause. PD was defined as at least a 20% increase in sum of longest diameter of target lesions as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 guidelines. Time to disease progression was censored at the date of death. | Randomization to measured PD up to 38 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Tumor Response of Complete Response (CR) or Partial Response (PR) [Tumor Response Rate (TRR)] | TRR was defined as the number of responders (complete or partial) divided by the number of participants qualified for tumor response, as assessed using the RECIST version 1.0 guideline, multiplied by 100. RECIST guidelines: CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions; PR was defined as at least a 30% decrease in sum of longest diameter of target lesions. | Randomization to measured disease progression up to 38 months | 
| Overall Survival (OS) | OS is defined as the time from randomization to the date of death from any cause. | Baseline to date of death from any cause up to 45.5 months | 
| Number of Participants With Adverse Events | A summary of serious and all other non-serious adverse events (AEs), which include AEs reported for pharmacological toxicity, is located in the Reported Adverse Event module. | Randomization up to 39 months | 
| Percentage of Participants With CR, PR, and Stable Disease (SD) - Disease Control Rate (DCR) | DCR was defined as the percentage of participants with CR, PR, or SD divided by the number of randomized and treated participants as assessed using the RECIST criteria. CR was defined as the disappearance of all target lesions; PR was defined as 1) at least a 30% decrease in sum of longest diameter of target lesions or 2) complete disappearance of target lesions, with persistence (but not worsening) of 1 or more non-target lesions; PD was defined as at least a 20% increase in sum of longest diameter of target lesions; SD was defined as small changes that did not meet the above criteria. | Randomization to disease progression up to 38 months | 
| Time to Worsening of Symptoms (TWS) on Lung Cancer Symptoms Scale (LCSS) | TWS assessed using the LCSS a participant rated lung cancer instrument which consisted of 9 disease related symptoms and quality of life (QoL) items, with 6 subscales related to major lung cancer symptoms (appetite, cough, fatigue, dyspnea, hemoptysis, and pain) and 3 summation items related to QoL (activity status, symptomatic distress, and overall QoL). Each item is marked on a visual analog scale (VAS) 0 (low symptoms/QoL items) to 100 (high symptoms/QoL items). The mean of the 6 subscales is used to calculate the average symptom burden index. TWS was measured from the date of study enrollment to the first date of a worsening in any 1 of the 6 LCSS symptom-specific items (as defined by a VAS 15-mm increase from baseline in the patient-reported score for any of these 6 items). | Randomization to first date of worsening of any of 6 LCSS symptom specific items or up to 12.4 months | 
| Number of Participants With Mutated or Non-Mutated Epidermal Growth Factor Receptor (EGFR) Genotype Status | EGFR mutation status was defined as: participants with any mutations detected were categorized as mutated and participants without any mutations detected were categorized as non-mutated. | Randomization to date of PD or death up to 38 months | 
| Probability of OS at 12 Months | OS time is censored at the date of last contact for participants who were still alive or lost to follow-up. | Month 12 |