Hydroxychloroquine + Carboplatin, Paclitaxel and Bevacizumb in Non-Small Cell Lung Cancer (NSCLC)

The purpose of this study is to examine the combination of one standard treatment for lung
cancer plus an additional drug, hydroxychloroquine. The standard treatment for lung cancer
being used includes 2 chemotherapy drugs, called paclitaxel and carboplatin, plus a drug
that targets blood vessels, called bevacizumab (also known as avastin).

Recent medical science suggests that the investigators may be able to make anticancer
therapy work better if they can block autophagy. Autophagy is a cellular process that helps
normal cells live through times of stress, for example during times of starvation. Studies
suggest that cancer cells may take advantage of autophagy to survive longer and to survive
despite treatment with chemotherapy. The investigators want to know if blocking autophagy
while giving standard treatment for lung cancer will improve the treatment of lung cancer.
The investigators will use hydroxychloroquine, which blocks autophagy, in addition to
standard treatment in the treatment of lung cancer.

The primary endpoint is to determine the recommended Phase II dose of paclitaxel,
carboplatin, bevacizumab in combination with hydroxychloroquine in patients with advanced or
recurrent NSCLC.

The primary objective of this study is to assess the antitumor activity, as measured by
tumor response rate, of paclitaxel, carboplatin, bevacizumab and hydroxychloroquine in
patients with advanced or recurrent NSCLC cancer.

Secondary Endpoint(s):

- To measure time to progression, percent one-year survival and overall survival.

- To assess toxicity of this regimen.

- To develop pharmacodynamic markers for autophagy detection in patient specimens.

- To characterize the effects of hydroxychloroquine on autophagy in patients in vivo.