Background: - The current standard of care for advanced lung cancer and cancers of the thymus consists primarily of chemotherapy treatment. The drugs used for chemotherapy depend on the classification of the cancer in different categories that are based on the appearance of the cancer in the microscope. Though this approach has been proved to be useful in some ways, the survival rates of individuals with lung cancer and cancers of the thymus are still very poor. Recent research has shown that several genetic abnormalities play an important role in the development and growth of lung cancer and cancers of the thymus, and that it is possible to improve treatment success rates with drugs that specifically target some of the abnormal genes. Researchers are interested in determining whether it is possible to analyze the genes of patients with lung cancer and cancers of the thymus in order to provide personalized treatment with drugs that target the specific gene abnormalities. Objectives: - To evaluate the effectiveness of genetic analysis in determining targeted therapy for individuals with advanced non-small cell lung cancer, small cell lung cancer, and thymic cancer. Eligibility: - Individuals at least 18 years of age who have been diagnosed with either lung cancer or a cancer of the thymus that is not considered to be curable with the use of surgery or radiation therapy. Design: - Participants will be screened with a full medical history and physical examination, blood and urine tests, and tumor imaging studies. Participants will have a tumor biopsy or provide previously collected tumor tissue for study. - Based on the results of the tumor biopsy study, participants will be separated into different treatment groups: - Participants with EGFR gene mutation will receive a drug called erlotinib, which inhibits a protein called EGFR that is thought to be a key factor in the development and progression of some cancers. - Participants with KRAS, BRAF, HRAS, or NRAF gene mutations will receive a drug called AZD6244, which inhibits a protein called MEK that is thought to be a key factor in the development and progression of some cancers. - Participants with PIK3CA, AKT, or PTEN gene mutations will receive a drug called MK-2206, which inhibits a protein called AKT that is thought to be a key factor in the development and progression of some cancers. - Participants with KIT or PDGFRA gene mutations will receive a drug called sunitinib, which inhibits some proteins that are thought to be key factors in the development and progression of some cancers, including kidney cancer. - Participants who have ERBB2 gene mutation or amplification will receive a drug called lapatinib, which inhibits some proteins that are thought to be key factors in the development and progression of some cancers, including breast cancer. - Participants who do not have any of the genetic abnormalities described above will be offered different options for treatment, including standard of care chemotherapy or treatment with investigational agents in a different research protocol. - After 6 weeks of treatment, participants will have imaging studies to evaluate the status of their cancer. Treatment will continue as long as participants tolerate the drugs and the disease does not progress. - Participants who benefit from the first treatment but eventually develop resistance and progression of their cancer will be offered the chance to have a second tumor biopsy and undergo a different treatment for their cancer.

NCT01306045

Conditions

1. Carcinoma, Non-Small-Cell Lung
2. Carcinoma, Small Cell Lung
3. Carcinoma, Thymic

Interventions

1. Drug: AZD6244
2. Drug: MK-2206
3. Drug: Lapatinib
4. Drug: Erlotinib
5. Drug: Sunitinib
6. Procedure: Molecular Profiling

MeSH:Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung Small Cell Lung Carcinoma Carcinoma, Small Cell Thymoma

HPO:Carcinoma Neoplasm of the lung Non-small cell lung carcinoma Small cell lung carcinoma Thymoma

- Individuals are eligible for 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). --- T790M --- --- V843I --- --- R831C --- --- R776G ---