Background: - PF-02341066 and PF-00299804 are drugs that specifically target certain proteins that may be more active in cancer cells than normal cells, in particular in non-small cell lung cancer. Both drugs seem to be able to stop the growth of or kill cancer cells. Researchers want to combine them to see if they are a safe and effective treatment for advanced non-small cell lung cancer. Objectives: - To test the safety and effectiveness of PF-02341066 and PF-00299804 for advanced non-small cell lung cancer. Eligibility: - Individuals at least 18 years of age with advanced non-small cell lung cancer that has not responded to standard treatments. Design: - Participants will be screened with a medical history and physical exam. They will also have blood and urine tests, and imaging studies. Heart and lung function tests and an eye exam may also be given. - The first cycle of treatment will be 28 days. Every cycle after the first will be 21 days. Participants may have up to 17 cycles of treatment. - Participants will take both study drugs as tablets. Twelve hours after the first dose, participants will take only the PF-02341066. This dose schedule will remain the same throughout the study. - Participants will be monitored with frequent blood and urine tests and imaging studies. Tumor biopsies will be taken as needed. Those in the study will keep a diary to record any symptoms or side effects of taking the study drugs. - After 17 cycles of treatment, or after stopping the study drugs early for any other reason, participants will have a final followup visit.
Single Group Assignment
There is one SNP
Biomarkers in tumor and blood that are potentially predictive for drug activity: for example, KRAS mutations, EGFR mutations (eg, T790M), EGFR and HER2 amplifications, c Met amplification and mutations, ALK, PTEN and PIK3A status in tumor biopsi.... null. --- T790M ---
- Despite the dramatic initial response to gefitinib and erlotinib, about 50% of NSCLC tumors develop resistance due to secondary activating mutations in EGFR itself, including the EGFR T790M gatekeeper mutation, and more than 20% of acquired resistance is due to an increase in mesenchymal-epithelial transition factor (c-Met) signaling. --- T790M ---
- There is evidence from a limited number of tumors from patients with acquired resistance to EGFR-TKIs that both T790M and cMET resistance mechanisms can occur in the same patient at different metastatic sites and even in different fractions of the same lesion. --- T790M ---
- Tumors with acquired resistance to erlotinib and gefitinib might be vulnerable to a combination of PF-00299804 a second generation EGFR TKI which is also an inhibitor of T790M mutation, and PF-02341066 which is an inhibitor of c- Met/Hepatocyte Growth Factor Receptor (HGFR). --- T790M ---