There are 2 clinical trials
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.
- 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 ---
Description: The feasibility rate for the trial will be evaluated by determining the percentage of enrolled patients with a successful molecular profile determined.Measure: To determine the feasibility of the use of tumor molecular profiling and targeted therapies in the treatment of NSCLC, SCLC, and Thymic Malignancies Time: 5 years
Description: Efficacy will be determined by assessing if patients who have treatment assigned on the basis of their molecular profiling results will exhibit reasonable response rates to the drug selected for their particular profile.Measure: To estimate the response rate of molecular-profile directed treatments in NSCLC, SCLC, and Thymic Malignancies Time: 5 years
Lung cancer is a common malignancy that is associated with cigarette smoking but can also affect individuals who never smoked. It is not well understood whether there are hereditary risk factors that influence the risk of lung cancer. It has been recently found that a small number of families have an inherited (passed from parent to child) change in one of their genes that may contribute to an increased tendency to develop lung cancers, even in never smokers. In some lung cancer patients this gene, called "EGFR", contains a DNA change known as an "inherited EGFR mutation". Early data indicate that these inherited EGFR mutations may be associated with an increased risk of lung cancer. So far, only a small number of families have been found to carry inherited EGFR mutations. For this reason the risk of lung cancer associated with inherited EGFR mutations is not well understood. Understanding the risk may help investigators find ways of detecting lung cancer sooner or reducing the risk of developing lung cancer. It was recently discovered that lung cancer patients who are found to carry one rare EGFR mutation in their cancer cells, called "T790M", have an increased risk of carrying an inherited EGFR mutation in their normal cells as well. This represents a new strategy for finding individuals and families carrying inherited EGFR mutations. This research study is designed to find cancer patients whose tumors have this EGFR mutation, T790M, to find out if they also have an inherited EGFR mutation. Subjects will not have to undergo a biopsy to participate in this research study. Investigators will collect a saliva specimen from patients with a T790M in their cancer to find out if they also have an inherited EGFR mutation. Study participants found or known to carry an inherited EGFR mutation will have the option of offering their close relative the opportunity to also participate in this study. Close relatives can consider testing to see if they also carry the inherited mutation in their normal cells. Once investigators have identified individuals and relatives that carry inherited EGFR mutations in their genes, investigators will then try to understand the risk of lung cancer and other cancers. Individuals with inherited EGFR mutations will also have the opportunity to participate in future studies related to cancer and other diseases. This study is being funded in part by the Conquer Cancer Foundation of ASCO and the Bonnie J. Addario Lung Cancer Foundation.
To study individuals and families with rare germline mutations, such as EGFR V843I and EGFR R776H. --- V843I ---
Description: To determine the prevalence of germline EGFR mutations in lung cancer patients with EGFR T790M mutations in their tumor and in relatives of carriers of germline EGFR mutationsMeasure: Prevalence of EGFR mutations Time: 2 years
Description: To make a preliminary assessment of the natural history of lung cancers occurring in patients with germline EGFR mutationsMeasure: Preliminary Assessment of History of Lung Cancers Time: 2 years
Description: To generate an initial estimate of the prevalence of CT-detected lung nodules in individuals with germline EGFR mutationsMeasure: Estimate of Prevalence of Lung Nodules Time: 2 years
Description: To study EGFR expression in skin biopsies from patients on studyMeasure: Study EGFR Expression in Skin Biopsies Time: 2 years
Description: To explore the relationship between high allelic fraction T790M on plasma genotyping and presence of an underlying germline EGFR T790M mutationMeasure: Explore Relationship Between High Allelic Fraction T790M in plasma genotyping and germline mutations Time: 2 years
Description: To study individuals and families with rare germline mutations, such as EGFR V843I and EGFR R776HMeasure: Examine Lung Cancer Risk Associated with Other Germline Mutations Time: 2 years