There are 2 clinical trials
This is a single center and exploratory study, aiming to analyze the efficacy and safety of dacomitinib-a pan-HER and irreversible TKI in subjects with diagnosed stage IIIB/IV or recurrent NSCLC. All subjects will have tumors that test positive for at least one uncommon EGFR activating mutation (do not have drug-resistant pattern, e.g. 20 insertion or 20T790M). All patients will be of histo- and/or cytopathology confirmed. Determination of the EGFR mutation type will be performed in the pathological department of Shanghai Chest Hospital. Both ARMS method or targeted sequencing are acceptable. It is not acceptable for subjects with the presence of the exon 20T790M mutation or insertion together with either EGFR activating mutations (exon 19 deletion or the L858R mutation in exon 21) or uncommon EGFR mutations. 10ml peripheral blood must be available for concomitant study. All eligible subjects must have adequate renal, hepatic, and hematologic function, as defined in "inclusion criteria". Patients will receive continuous oral therapy with the study drugs (dacomitinib 45 mg) until progressive disease as defined by RECIST version 1.1 or judged by investigator that the patient no longer derives clinical benefit from study treatment. At the time of progression and removal from study treatment, the subject may receive any regulatory approved therapy at the judgment of the investigator. Timely and complete disease assessments in this study are important. Every effort should be made to ensure disease assessments performed as scheduled to prevent the introduction of bias into the assessment of efficacy. Failure to perform any of the required disease assessments will result in the inability to determine disease status for that time point. Frequent off schedule or incomplete disease assessments have the potential to weaken the study conclusion. Subjects who have progressive disease per RECIST version 1.1 confirmed by the investigator believes it is in their best interest to continue on their study therapy, will be allowed to continue on their therapy with or without local therapy (e.g. surgical removal and/or radiation of a single lesion), at the discretion of the investigator until any alternate or additional systemic anti-cancer therapy regimen is implemented. The subsequent new cancer therapy (including, for systemic therapy, drugs administered, date of initiation and discontinuation of each drug) and OS will be recorded. Each subject will be followed for survival status and subsequent cancer therapies up to 48 months from the date of first dosing. This data may be collected from subjects by telephone, and if collected should be entered into the CRF.
Mutation in exon 20: Including S768I, V765A, T783A, V774A, S784P, R776C, R776H, V765M, G779C, G779F, G779S, T783A, T783I, L798F, L798H, K806E, Q812R, L814P Mutation in exon 21: L861Q, R831H, V834I, L838P, L861R. --- S768I --- --- V765A --- --- T783A --- --- V774A --- --- S784P --- --- R776C --- --- R776H ---
Description: ORR was defined as the proportion of patients with a complete response (CR) or partial response (PR) per the investigator's assessment using RECIST 1.1 criteriaMeasure: Objective response rate （ORR） Time: 6-12 weeks
Description: The disease control rate (DCR) was defined as the sum of the proportions of patients who had CR, PR, and stable disease (SD) using RECIST 1.1 criteriaMeasure: Disease control rate Time: 6-12 weeks
Description: PFS was defined as the time from study treatment initiation to the first occurrence of documented disease progression or death from any cause during the study, whichever occurred first.Measure: PFS Time: 13-15months
Description: OS was defined as the time from the first dose of study treatment to the time of death from any cause during the study.Measure: Overall survival Time: 22-25months
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 --- --- R776H ---
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