There is one clinical trial.
The investigators propose to conduct a retrospective study of single agent ceritinib in patients with previously untreated anaplastic lymphoma kinase (ALK) rearranged adenocarcinoma of the lung with the sole purpose of characterizing the genomic landscape before ceritinib and at the time of disease progression.
Recently, secondary ALK mutations, L1196M and G1269A have been described in patients with acquired resistance to crizotinib. --- L1196M ---
Description: The investigators will compare tumor sequencing prior to ceritinib treatment to the time of disease progression to see if the genetic sequencing changed between pre-treatment and progression. The investigators plan to conduct exome and transcriptome sequencing of tumor before therapy with certitinib and at the time of relapse. In addition, exome sequencing of peripheral blood DNA will be done (for germline). Given the complexities of genomic analyses of paired samples in the face of limited data, the investigators will not be able to do any formal power calculations in this feasibility study. Disease progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.Measure: Genetic changes associated with disease progression following treatment with ceritinib Time: Estimated to be 1 year
Description: Investigators will look at tumor tissue associated with a therapeutic response and compare with tumor tissue associated with disease progression and see if there are any mutation differences. Therapeutic Response Complete response is disappearance of all target lesions and non-target lesions. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.Measure: Types of mutations in signaling kinases associated with therapeutic response Time: Estimated to be 1 year
Description: A variant is considered to have mutant biased expression if the variant is expressed and the variant allele frequency is greater than 20% higher in the RNA-seq data compared to the exome sequencing data. A variant is considered to have wild type biased expression if the gene is expressed, the region of the variant is covered at 5X or greater depth, and the VAF is at least 20% lower in the RNA-seq data compared to the exome sequencing data. Duration of response is the duration of overall response is measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).Measure: Allelic ratio of wild type ALT to ALK gene rearrangement (roughly corrected for intrinsic difference in tumor cellularity) with duration of response Time: Estimated to be 1 year