In 2009, there were 219,000 new lung cancer cases reported. Roughly one-quarter of these patients will be considered candidates for "curative" surgical resection, where the preservation of lung function must be balanced against the extent of tissue removed. As a result, patients requiring these limited resection procedures suffer a high risk of developing local tumor recurrence, including early stage patients (16% local recurrence rate), due to the increased presence of microscopic tumors cells remaining at or near the resection margin. Recurrent lung cancer is resected if possible, but the extent of disease or inadequate pulmonary function often limits treatment to palliative chemotherapy or external radiation therapy. There is currently no established standard of care for preventing locoregional tumor recurrence following resection. Fifth Base has developed a unique, and simple to use, drug eluting implant that reduces the incidence of locoregional cancer recurrence by locally delivering therapeutic levels of drug to the site of highest risk of recurrence for over several months. The local delivery of chemotherapeutic drugs to the resection margins would reduce the significant side effects associated with systemic administration, change the paradigm to "see and treat" at the time of surgery, allow the surgeon to excise a smaller margin while treating the residual tumor burden effectively and locally, reducing the tumor recurrence while preserving lung function. Fifth Base proposes to advance our technology down the path of commercialization by the completion of the following Phase II proposed aims: 1) scale-up of monomer synthesis, 2) cGMP large scale synthesis of polymer with in-process validations, 3) performance of chemistry, manufacturing, and controls validations required for drug-eluting devices, 4) performance of FDA-required ISO-compliant biocompatibility studies including in vivo chronic toxicity, and 5) investigation of pharmacokinetic, distribution, and excretion of paclitaxel following orthotopic implantation of the drug-loaded polymer implant in a large animal lung model. With the successful completion of the key technological objectives in this Phase II SBIR proposal, along with work currently being performed in parallel, we will produce a batch of cGMP manufactured and packaged devices and performed nearly the complete battery of preclinical safety and toxicity testing required by the FDA for regulatory approval sufficient to initiate clinical trials. Phase III will consist of a large animal safety study, obtainment of IDE/IRB clinical site approval, followed by the Phase I first-in-human clinical safety trial.
Fifth Base has developed a unique, and simple to use, drug-eluting implant that reduces the incidence of locoregional lung cancer recurrence by locally delivering therapeutic levels of drug to the site of disease for over several months. Locoregional tumor recurrence after a surgical lung resection is a significant clinical problem in the management of early stage lung cancer patients. Our device will be implanted at the time of surgery using standard procedures and surgical tools and enables a new paradigm of low toxicity, preventative treatment at the site of highest risk of tumor recurrence.