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

Study Overview
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Brief Summary
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This study will compare the efficacy and safety of Tarceva (erlotinib) and vinorelbine in chemo-naive elderly patients with advanced non-small cell lung cancer. Patients will be randomized to receive either Tarceva (150 mg po daily) or vinorelbine (60 mg/m2 on days 1 and 8 of cycle 1 and 80 mg/m2 for the other 21 days cycles). The anticipated time on study treatment is until disease progression.

Official Title
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A Phase II Randomized Trial of Erlotinib or Vinorelbine in Chemo-naive, Advanced, Non-Small-Cell Lung Cancer Patients Aged 70 Years or Older in Taiwan

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: erlotinib [Tarceva]
* Drug: vinorelbine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, >=70 years of age Non-small cell lung cancer Naive to prior chemotherapy or specific immunotherapy Presence of at least 1 measurable lesion Exclusion Criteria: Active non-controlled infection or disease CNS metastases Any other malignancies (other than adequately treated basal cell cancer of skin, or in situ cancer of the cervix)

Ages Eligible for Study
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Minimum Age: 70 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: 1<br> | Drug: erlotinib [Tarceva]<br>* 150 mg, orally once a day for up to 6 cycles of 21 days each<br>|
| Active Comparator: 2<br> | Drug: vinorelbine<br>* 60 mg/m2, orally on days 1 and 8 of cycle 1, 80 mg/m2 for the other cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a Best Overall Response of Complete Response (CR) or Partial Response (PR) | CR was defined as disappearance of all target lesions. PR was defined as at least a 30 percent (%) decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Participants experiencing either a CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST) were classified as responders. Participants with tumour assessment unevaluable were viewed as non-responders. | Screening, Day 1 of Cycles 3 and 5 and at End of treatment up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Disease Control | Disease control was defined as achieving a best overall response of CR, PR, or stable disease (SD) according to RECIST criteria. Participants with tumor assessment unevaluable were viewed as uncontrolled. | Screening, Day 1 of Cycles 3 and 5 and at End of treatment up to 1 year | 
| Duration of Response Among Participants Who Achieved Either a CR or PR | Duration of response was defined similarly for complete and partial responders. Complete response lasted from the date the complete response was first recorded to the date on which progressive disease was first noted or date of death. Partial response lasted from the date of partial response to the date of the first observation of progressive disease or date of death. | Screening, Day 1 of Cycles 3 and 5, every 4th cycle during post-study treatment, and every 3 cycles during follow-up | 
| Percentage of Participants With Disease Progression | Progressive disease was defined using RECIST as at least a 20% increase in the sum of the 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. | Day 1 of Cycles 1, 3, and 5 or first documentation of progressive disease or death | 
| Time to Disease Progression | Time to disease progression was defined as the interval between the day of randomization and the first documentation of progressive disease or death. | Day 1 of Cycles 1, 3, and 5 or first documentation of progressive disease or death | 
| Overall Survival: Percentage of Participants With an Progressive Disease or Death | Overall survival was defined as the time from the date of randomization to the date of death. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last dose and participants with no postbaseline information were censored at the time of randomization. Progressive disease was defined per RECIST as at least a 20% increase in the sum of the 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. | Day 1 of Cycles 1 through 6 to date of death or date of last follow-up assessment | 
| Overall Survival: Time to Event | Overall survival was defined as the time from the date of randomization to the date of death. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last dose and participants with no post baseline information were censored at the time of randomization. Overall median time to event was assessed for the population that experienced an event. | Day 1 of Cycles 1 through 6 to date of death or date of last follow-up assessment | 
| Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire | The FACT Questionnaire contains 4 general and 1 lung cancer symptom-specific subscale, including Physical Well-Being (PWB), Social/family Well-Being (SWB), Emotional Well-Being (EWB), Functional Well-Being (FWB), and the 8-item Lung Cancer Subscale (LCS) that assess symptoms commonly reported by participants with lung cancer. Each subscale was assessed by a five-point scale from 0 (not at all) to 4 (very much) to determine the quality of life. PWB, SWB and FWB scores ranged from 0-28 and EWB scores ranged from 0-24. LCS scores ranged from 0-36. For subscales of FWB and SWB, questionnaires of EWB, and additional concerns questions, the higher score represented 'Improved'. For other subscales and questionnaires, the higher score represented 'Worsened'. Missing data were replaced by the valid post-baseline assessment before. The FACT-L score ranges from 0 to 136, with higher scores indicating better quality of life. | Baseline and Day 1 of Cycles 2, 3, 4, 5, 6 and End of study | 
| Changes in Quality of Life as Measured by the FACT Questionnaire | The FACT Questionnaire contains 4 general and 1 lung cancer symptom-specific subscale, including PWB, SWB, EWB, FWB, and the 8-item LCS that assess symptoms commonly reported by participants with lung cancer. Each subscale was assessed by a five-point scale from 0 (not at all) to 4 (very much) to determine the quality of life. PWB, SWB and FWB scores ranged from 0-28 and EWB scores ranged from 0-24. LCS scores ranged from 0-36. For subscales of FWB and SWB, questionnaires of EWB, and additional concerns questions, the higher score represented 'Improved'. For other subscales and questionnaires, the higher score represented 'Worsened'. Missing data were replaced by the valid post-baseline assessment before. For PWB, FWB, SWB, and EWB scores and disease-specific subscale score, response of down, up or no change were defined as score changes of less than or equal to (≤)2, greater than or equal to (≥)+2, or between these values. | Baseline and Day 1 of Cycles 2, 3, 4, 5, 6 and End of study | 
| Percentage of Participants With Changes in Quality of Life as Measured by FACT Questionnaire Scores by Category of Change | The FACT and the FACT-L contain 4 general and 1 lung cancer symptom-specific subscale, including PWB, SWB, EWB, FWB, and the 8-item LCS that assess symptoms commonly reported by participants with lung cancer. For subscales of FWB and SWB, questionnaires of EWB, and additional concerns questions, the higher score represented 'Improved'. For other subscales and questionnaires, the higher score represented Worsened'. For PWB, FWB, SWB, and EWB scores and disease-specific subscale score, higher scores indicated a better outcome; a response of down, up, or no change was defined as a score change of ≤ -2 (score down), ≥ +2 (score up), or between these values. | Baseline and End of study | 
| Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire | The LCS consists of 7 items of the FACT-L (3 items relating to breathing/dyspnea, and 1 item each relating to cough, weight loss, appetite, and cognition) rated on a five-point scale from 0 (not at all) to 4 (very much). The LCS total score is the sum of the scores from the 7 items. For clear thinking and good appetite, the higher score represented 'Improved'; for other subscales and questionnaires, the higher score represented 'Worsened'. Missing data were replaced by the valid post-baseline assessment before. The change of FACT-L subscore was the change from baseline to endpoint. The LCS of FACT-L is an independently validated tool that measures the disease-related symptoms of lung cancer on an overall scale of 0 (most symptomatic) to 28 (asymptomatic). | Baseline and Day 1 of Cycles 2, 3, 4, 5, 6 and End of study | 
| Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change | The LCS consists of 7 items of the FACT-L (3 items relating to breathing/dyspnea, and 1 item each relating to cough, weight loss, appetite, and cognition). The LCS total score is the sum of the scores from the 7 items, each rated on a five-point scale from 0 (not at all) to 4 (very much). For clear thinking and good appetite, the higher score represented 'Improved'; for other subscales and questionnaires, the higher score represented 'Worsened'. For each FACT-L question, the response status was defined as down, up, or no change if the score at endpoint was smaller (score down), larger than (score up), or the same as (no change) that at baseline. | Baseline and End of study |