A Study of Tarceva (Erlotinib) in Combination With Avastin (Bevacizumab) in Patients With Advanced Non-Small Cell Lung Cancer.

Study Overview
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Brief Summary
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This 2 arm study will compare the efficacy and safety of Tarceva plus Avastin, and chemotherapy plus Avastin, in the first-line treatment of patients with advanced non-small cell lung cancer. Patients will be randomized to receive either Tarceva 150mg p.o. daily plus Avastin 15mg/kg i.v. every 3 weeks, or standard platinum-based chemotherapy (4-6 cycles) plus Avastin. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.

Official Title
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A Randomized, Open-label Study Comparing the Anti-tumor Effect of Treatment With Tarceva Plus Avastin Versus Chemotherapy Plus Avastin in Patients With Advanced Non-small Cell Lung Cancer

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Erlotinib
* Drug: Bevacizumab
* Drug: Standard platinum-based chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >=18 years of age; advanced (stage IIIb and IV) non-small cell lung cancer; measurable disease; ECOG PS 0-1. Exclusion Criteria: prior chemotherapy or treatment with another systemic anti-cancer agent; radiotherapy within 4 weeks prior to first dose of study treatment; CNS metastases; other malignancies in past 5 years, except for adequately treated cancer in situ of the cervix, basal or squamous cell skin cancer.

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 |
| --- | --- |
| Active Comparator: Bevacizumab, Chemotherapy<br>Participants received bevacizumab, 15 milligrams (mg) per (/) kilogram (kg), intravenously (IV), on Day 1 of Cycles 1 through 7 until disease progression, unacceptable toxicity, death, or withdrawal. Participants also received 4 to 6 cycles of a standard platinum-containing regimen of chemotherapy: either gemcitabine, 1250 mg/ square meter (m^2), IV, on Days 1 and 8 of Cycles 1 through 4 or 6, and cisplatin 80 mg/m^2, IV, on Day 1 of Cycles 1 through 4 or 6; or paclitaxel, 200 mg/m^2, IV, and carboplatin area under the curve (AUC) 6 mg/ milliliter (ml) multiplied by (*) minute (min) on Day 1 of Cycles 1 through 4 or 6. The chemotherapy regimen and number of cycles was up to the discretion of the investigator. | Drug: Bevacizumab<br>* 15 mg/kg, IV, Day 1 of Cycles 1 through 7<br>* Other names: Avastin;Drug: Standard platinum-based chemotherapy<br>* At the discretion of the investigator<br>|
| Experimental: Bevacizumab, Erlotinib<br>Participants received bevacizumab, 15 mg/kg, IV, on Day 1 of Cycles 1 through 7 until disease progression, unacceptable toxicity, death, or withdrawal. Participants also received erlotinib, 150 mg, orally (PO), daily until disease progression, unacceptable toxicity, death, or withdrawal. | Drug: Erlotinib<br>* 150 mg, PO, daily<br>* Other names: Tarceva;Drug: Bevacizumab<br>* 15 mg/kg, IV, Day 1 of Cycles 1 through 7<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Disease Progression or Death | Progression-free survival (PFS) was defined as the time from randomization to disease progression or death, from any cause. Progressive disease (PD) was defined according to Response Criteria in Solid Tumors (RECIST) version (V) 1.0. For target lesions (TLs), progressive disease (PD) was defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded since the start of treatment. For non-target lesions (NTLs), PD was defined as unequivocal progression of existing NTLs. Participants were censored at the date of last post-baseline (BL) tumor assessment where non-progression was documented. If no post-BL tumor assessment was available, the participant was censored at date of randomization. | Screening, end of every 2nd cycle through Cycle 8 (21-day cycles), and every 12 weeks thereafter until the end of study and final analysis up to a maximum of 42 months. | 
| PFS | The median time, in weeks, from randomization to PFS event. Participants were censored at the date of last post-BL tumor assessment where non-progression was documented. If no post-BL tumor assessment was available, the participant was censored at date of randomization. PFS was estimated using Kaplan-Meier methodology. | Screening, end of every 2nd cycle through Cycle 8 (21-day cycles), and every 12 weeks thereafter until the end of study and final analysis up to a maximum of 42 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Died | Overall survival (OS) was defined as the time from randomization to the date of death, due to any cause. Participants were censored at final analysis at the date the participant was last known to be alive. | Screening, Days 1, 8, and 21 of Cycles 1-8 (21-day cycles), and every 12 weeks thereafter until the end of study and final analysis up to a maximum of 42 months. | 
| OS | The median time, in months, from randomization to OS event. Participants were censored at final analysis at the date the participant was last known to be alive. | Screening, Days 1, 8, and 21 of Cycles 1-8 (21-day cycles), and every 12 weeks thereafter until the end of study and final analysis up to a maximum of 42 months. | 
| Percentage of Participants With a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR) According to RECIST V 1.0 | BOR was defined as the best response recorded from randomization until disease progression/recurrence or death, taking as reference for PD the smallest measurement (nadir) recorded since treatment started. Assignment of PR of CR required confirmation of tumor measurement changes by repeat assessments performed no less than 4 weeks after criteria for response was first met. For TLs, CR was defined as the disappearance of all TLs; and PR was defined as at least a 30% decrease in the SLD of the TLs, taking BL SLD as reference. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. The 95% CI for one sample binomial was calculated using the Pearson-Clopper method. | Screening, end of every 2nd cycle through Cycle 8 (21-day cycles), and every 12 weeks thereafter until the end of study and final analysis up to a maximum of 42 months. | 
| Percentage of Participants With Disease Control According to RECIST V 1.0 | Disease control was defined as a BOR of CR, PR, or SD according to RECIST V 1.0 for at least 4 weeks at any time during randomized treatment or disease stabilization, after study entry. Participants without a post-BL assessment of response were considered as having no disease control. The 95% CI for the one sample binomial was calculated using the Pearson-Clopper method. | Screening, end of every 2nd cycle through Cycle 8 (21-day cycles), and every 12 weeks thereafter until the end of study and final analysis, 12 months after the last participant's 1st visit |