A Study of Tarceva (Erlotinib) in Combination With Platinum Based Chemotherapy in Patients With Non-Small Cell Lung Cancer.

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of sequential administration of Tarceva and gemcitabine/platinum chemotherapy in patients with stage IIIb/IV non-small cell lung cancer. Patients will be randomized to receive Tarceva (150 mg po) or placebo on days 15-28 of a 4 week cycle of intravenous platinum-based chemotherapy, for a total of 6 cycles. The anticipated time on study treatment is until disease progression or unacceptable toxicity.

Official Title
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A Randomised, Placebo-controlled, Double-blind Phase II of Sequential Administration of Tarceva (Erlotinib) or Placebo in Combination With Gemcitabine/Platinum as First-line Treatment in Patients With Stage IIIB/IV Non-small Cell Lung Cancer (NSCLC).

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: erlotinib [Tarceva]
* Drug: placebo
* Drug: gemcitabine
* Drug: cisplatin
* Drug: carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >=18 years of age; histologically documented advanced or recurrent stage IIIB or IV non-small cell lung cancer; measurable disease; no previous chemotherapy for non-small cell lung cancer. Exclusion Criteria: unstable systemic disease; any other malignancies in the last 5 years.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tarceva + gemcitabine/platinum<br> | Drug: erlotinib [Tarceva]<br>* 150 mg orally daily Days 15 to 28 of each 4-week cycle for 6 cycles, followed by 150 mg orally daily<br>Drug: gemcitabine<br>* 1250 mg/m2 iv Days 1 and 8 of each 4-week cycle, 6 cycles<br>Drug: cisplatin<br>* 75 mg/m2 iv Day 1 of each 4.wek cycle, 6 cycles; or carboplatin<br>Drug: carboplatin<br>* 5 x AUC iv Day 1 of each 4.week cycle, 6 cycles; or cisplatin<br>|
| Placebo Comparator: Placebo + gemcitabine/platinum<br> | Drug: placebo<br>* orally daily Days 15 to 28 of each 4-week cycle for 6 cycles, followed by daily oral application<br>Drug: gemcitabine<br>* 1250 mg/m2 iv Days 1 and 8 of each 4-week cycle, 6 cycles<br>Drug: cisplatin<br>* 75 mg/m2 iv Day 1 of each 4.wek cycle, 6 cycles; or carboplatin<br>Drug: carboplatin<br>* 5 x AUC iv Day 1 of each 4.week cycle, 6 cycles; or cisplatin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Non-Progression at Week 8 as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) | Non-progression defined as documented best overall tumor response of complete response (CR), partial response (PR), or stable disease (SD; where SD was maintained for greater than [>]8 weeks) per RECIST. Investigator's assessment of response used in all analyses. CR equals (=)disappearance of all target lesions; PR=at least a 30 percent (%) decrease in sum of longest diameter (LD) of target lesions, taking as reference the baseline sum LD; SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference smallest sum LD since treatment started. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Non-Progression at Week 16 as Assessed by RECIST | Non-progression defined as documented best overall tumor response of CR, PR, or SD (where SD was maintained for >16 weeks) per RECIST. | Week 16 | 
| Percentage of Participants With Confirmed CR or PR as Assessed by RECIST | CR=disappearance of all target lesions; PR=at least a 30% decrease in sum of LD of target lesions, taking as reference the baseline sum LD. | Screening/Baseline, Day 22 of Cycles 2, 4 and 6 and every 8 weeks in Post-Study and Off-Study Phases | 
| Duration of Response | Duration of Response was defined similarly for complete responders and partial responders. CR was defined as the date CR was first recorded to the date on which PD was first noted or date of death. PR was defined as the date the first PR was recorded to the date of the first observation of PD or date of death. | Screening/Baseline, Day 22 of Cycles 2, 4 and 6 and every 8 weeks in Post-Study and Off-study Phases | 
| Time to Progression | Time to progression was defined as the interval between the day of randomization and the first documentation of PD. Participants who were withdrawn from the study without documented progression and for whom there exists CRF evidence that evaluations have been made, were censored at 1) the date of the last tumor assessment, 2) last date in the drug log, or 3) last date of follow-up when the participant was known to be progression free, whichever was last. Participants without post-baseline tumor assessments but known to be alive were censored at the time of randomization. | Screening/Baseline, Day 22 of Cycles 2, 4 and 6 and every 8 weeks in Post-Study and Off-Study Phases | 
| Progression-Free Survival (PFS) | PFS was defined as the interval between the day of randomization and the date of first documentation of progressive disease or date of death, whichever came first. | Screening/Baseline, Day 22 of Cycles 2, 4 and 6 and every 8 weeks in Post-Study and Off-Study Phases | 
| Overall Survival | Overall Survival (OS) was defined as the time from the date of randomization to the date of death, regardless of the cause of death. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment. | Date of randomization until date of death or date of last follow-up assessment |