Carboplatin, Paclitaxel, and Bevacizumab With or Without Erlotinib Hydrochloride in Treating Non-Smokers With Advanced Non-Small Cell Lung Cancer

OBJECTIVES:

Primary

- To evaluate the progression-free survival (PFS) of non-smokers with advanced non-small
cell lung cancer randomized to receive treatment with standard care (carboplatin and
paclitaxel with or without bevacizumab) or standard care in combination with erlotinib
hydrochloride.

Secondary

- To evaluate the overall survival of these patients.

- To evaluate the response rate in these patients.

- To evaluate the relative toxicity of these regimens in these patients.

- To determine the frequency of EGFR and Kras mutations in these patients and correlate
mutation status with response rate and PFS.

- To obtain blood and tissue specimens for further marker-based exploratory analyses
regarding EGFR inhibitors.

- To evaluate EGFR positivity by FISH as a predictor of improved PFS in patients treated
with erlotinib hydrochloride.

OUTLINE: This is a multicenter study. Patients are stratified according to gender and
eligibility for bevacizumab therapy (ineligible vs eligible and willing to receive
bevacizumab vs eligible and not willing to receive bevacizumab). Patients are randomized to
1 of 2 treatment arms.

- Arm I: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes
(with or without bevacizumab IV over 30-90 minutes) on day 1. Patients also receive an
oral placebo once daily on days 1-21. Treatment repeats every 21 days for 6 courses in
the absence of disease progression or unacceptable toxicity. After completion of 6
courses, patients with stable or responding disease may continue to receive placebo
(with or without bevacizumab) as above in the absence of disease progression or
unacceptable toxicity.

- Arm II: Patients receive paclitaxel and carboplatin (with or without bevacizumab) as in
arm I. Patients also receive oral erlotinib hydrochloride once daily on days 1-21.
Treatment repeats every 21 days for 6 courses in the absence of disease progression or
unacceptable toxicity. After completion of 6 courses, patients with stable or
responding disease may continue to receive erlotinib hydrochloride (with or without
bevacizumab) as above in the absence of disease progression or unacceptable toxicity.

Blood and tissue samples are collected for correlative laboratory studies.

After completion of study treatment, patients are followed up periodically for 5 years.