Intratumoral Gene Mediated Cytotoxic Immunotherapy (GMCI) For Resectable Non-Small Cell Lung Cancer

Surgery is the best treatment for patients with Stage I or II lung cancer; however, nearly 60% of patients have recurrence. Additional immunotherapeutic agents given before surgery may be greatly reduce recurrence. This is a Standard Phase I, 3+3 dose escalation trial designed to evaluate the safety and toxicity of neoadjuvant AdV-tk/valacyclovir. The primary end-point of the study is to determine maximum tolerated dose (MTD) and safety of AdV-tk/valacyclovir when combined with standard surgery and chemotherapy and/or radiation therapy. The secondary objectives are is to determine gene transfer efficiency and the effect of rAd-IFNa on the histology and immune profile of the resected tumor. We will also assess time to progression and overall survival. The study is focusing on patients presenting with resectable NSCLC (4 cm) who are considered to be good surgical candidates, but at high risk for recurrence. The primary tumor must be accessible for vector delivery at the time of standard-of-care staging procedure. The study drug in question is an Investigational New Drug (IND), AdV-tk. There will be a single dose of AdV-tk for intratumoral injection. The drug will be delivered at three levels (see protocol for dosages), followed by a standard dose of valacyclovir. At least 6 patients will be enrolled at the maximum tolerated dose (MTD) or the highest dose level if a MTD is not reached. The drug will be delivered during scheduled staging procedure via a transbronchial or surgical approach.