Molecular Profiling and Targeted Therapy for Advanced Non-Small Cell Lung Cancer, Small Cell Lung Cancer, and Thymic Malignancies

BACKGROUND: * A better understanding of the genetic make-up of the individual tumor may offer potentially improved therapies. This approach may also give rapid access to response data in patients with sometimes rare genetic abnormalities. * In addition, it will allow us to test targeted therapies in a select population of patients that is more likely to have a favorable response based on their molecular profile and the specific mechanism of action of the drug being tested. * This approach will also speed up drug development and potentially approval and rescue an otherwise ineffective drug candidate for the specific subgroup that can benefit. Primary Objectives: * To determine the feasibility of the use of tumors molecular profiling and targeted therapies in the treatment of advanced stage non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and thymic malignancies. * To estimate the response rate of molecular profile directed treatments in NSCLC, SCLC and thymic malignancies patients. ELIGIBILITY: * Patients with histologically confirmed advanced lung cancer or thymic malignancies for whom surgical resection with curative intent is not feasible. * Patients must either have biopsiable disease and be willing to undergo biopsy for molecular profiling or have paraffin embedded tissue blocks suitable for molecular profiling analysis. * Individuals are eligible for epidermal growth factor receptor (EGFR) germline mutation testing if they have: * a personal history of invasive lung cancer or one of the pre-invasive histologies associated with the development of lung cancer and more than two affected family members with invasive lung cancer or one of the pre-invasive histologies associated with the development of lung cancer, OR * a first-degree relative with a known EGFR germline mutation (EGFR exon 20 T790M, exon 21 V843I, exon 21 R831C and exon 20 R776G). DESIGN: * All patients will have their tumors undergo molecular profiling. Based on these results and on other eligibility criteria, the patients will be offered enrollment into different targeted therapy arms. * At the NCI site only, individuals eligible for EGFR germline mutation will undergo testing for germline mutations affecting the EGFR gene; if a mutation is detected, their first-degree relatives would be invited to undergo testing for the index germline mutation found in the proband and appropriate follow-up on trial. * Effective with Amendment I, the participating site, Oregon Health and Science University (OHSU), will discontinue new enrollments and data entry for existing patients on the Not Other Specified (NOS) arm on this protocol in favor of the OHSU protocol L8639, Personalized Cancer Medicine Registry. The data from these patients will be included with the data from 11-C-0096 (8639) National Cancer Institute (NCI) patients at the time of publication. Any OHSU patients who are eligible for a treatment arm will continue to be enrolled and followed per protocol.