SNPMiner Trials (Home Page)
Report for Mutation G1202R
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 3 clinical trials
Clinical Trials
1 Retrospective Analysis of Genomic Landscape of ALK Positive NSCLC Prior to Ceritinib, and at Disease Progression Following Ceritinib
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.
NCT02554591 Carcinoma, Non-Small-Cell Lung Non-small Lung Cancer Non-Small Cell Lung Cancer MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma
Secondary mutations found included G1202R, F1174C, and F1174V. --- G1202R ---
Primary Outcomes
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 yearSecondary Outcomes
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 yearDescription: 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 year2 AN EXPANDED ACCESS PROTOCOL FOR LORLATINIB FOR TREATMENT OF PATIENTS WITH ADVANCED NON-SMALL CELL LUNG CANCER HARBORING SPECIFIC MOLECULAR ALTERATIONS
This expanded access study has being designed following a demand from the FDA, given the increase in the number of request for single patient INDs for lorlatinib
NCT03178071 Non Small Cell Lung Cancer ALK Positive or ROS1 Positive Drug: Lorlatinib MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma
For patients with resistance mutations not covered by other inhibitors (eg, ALK G1202R resistance mutation), prior treatment with an ALK/ROS1 inhibitor is not required. --- G1202R ---
3 A Biomarker-Driven Protocol for Previously Treated ALK-Positive Non-Squamous NSCLC Patients: The NCI-NRG ALK Protocol
This National Cancer Institute (NCI)-NRG ALK Protocol phase II trial studies how well a combination of different biomarker/ALK inhibitors work in treating patients with stage IV ALK positive non-squamous non-small cell lung cancer. Lorlatinib, ceritinib, alectinib, brigatinib, ensartinib, and crizotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pemetrexed, cisplatin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether a combination of biomarker/ALK inhibitors or chemotherapy may work better in treating patients with ALK positive non-squamous non-small cell lung cancer.
NCT03737994 Lung Non-Squamous Non-Small Cell Carcinoma Stage IV Lung Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8 Drug: Alectinib Drug: Brigatinib Drug: Carboplatin Drug: Ceritinib Drug: Cisplatin Drug: Crizotinib Drug: Ensartinib Drug: Lorlatinib Drug: Pemetrexed MeSH:Lung Neoplasms
HPO:Neoplasm of the lung
OUTLINE: Patients with a G1202R or G1202del mutation receive either lorlatinib orally (PO) once daily (QD) or brigatinib PO QD. --- G1202R ---
Primary Outcomes
Description: Will be defined as the number of subjects whose best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of evaluable subjects per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. For each ALK inhibitor therapy, the primary analysis is to compare the response rate for the patients who have the relevant mutation (G1202/C1156Y /I1171/L1196/ V1180/F1174/compound mutation) to those patients who receive the same ALK inhibitor therapy who have no mutations using Fisher's exact test. For the no ALK-resistance mutation patients, the primary analysis is to compare patients who are randomized concurrently to the pemetrexed with cisplatin or carboplatin arm and the respective ALK inhibitor therapy arm. The response rates will be compared using Fisher's exact test. The ORR for each mutation/regimen combination and the associated 95% confidence intervals (using Clopper-Pearson method) will also be reported.
Measure: Objective response rate (ORR) Time: Up to 24 weeksSecondary Outcomes
Description: Will be assessed according to RECIST 1.1. Will be estimated for each mutation (or no mutation)/regimen combination. The Kaplan-Meier method will be used to estimate the distribution and median with 95% confidence intervals constructed through use of the Brookmeyer and Crowley method. PFS rates at specific time-points will also be estimated using the Kaplan-Meier method, with 95% confidence intervals calculated on the basis of Greenwood's estimate for the variance.
Measure: Progression-free survival (PFS) Time: From second step registration to the date of the first recorded occurrence of disease progression or death from any cause (whichever occurs first), assessed up to 7 yearsDescription: Will be assessed according to RECIST 1.1. Will be estimated for each mutation (or no mutation)/regimen combination. The Kaplan-Meier method will be used to estimate the distribution and median with 95% confidence intervals constructed through use of the Brookmeyer and Crowley method.
Measure: Duration of response Time: From the first occurrence of a documented BOR of CR or PR to the first date of recorded disease progression or death from any cause (whichever occurs first), assessed up to 7 yearsDescription: Will be estimated for each mutation (or no mutation)/regimen combination. The Kaplan-Meier method will be used to estimate the distribution and median with 95% confidence intervals constructed through use of the Brookmeyer and Crowley method. OS rates at specific time-points will also be estimated using the Kaplan-Meier method, with 95% confidence intervals calculated on the basis of Greenwood's estimate for the variance.
Measure: Overall survival (OS) Time: From second step registration to the date of death from any cause, assessed up to 7 yearsDescription: Will be defined as the rate of central nervous response (CNS) response among patients with known CNS metastasis but no prior CNS radiation therapy determined using modified RECIST 1.1. Will be estimated for each mutation (or no mutation)/regimen combination. The associated 95% confidence intervals (using Clapper-Pearson method) will also be reported.
Measure: Intracranial objective response rate Time: Up to 7 yearsDescription: Will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Adverse events will be summarized regardless of relationship to protocol treatment as assessed by the investigator. All adverse events, adverse events leading to withdrawal, interruption or modification of protocol treatment, grade >= 3 adverse events, and serious adverse events will be summarized. Deaths and cause of death will be summarized. The rate of treatment-related adverse events will be reported with the frequency and severity (e.g., type, grade, and attribution).
Measure: Incidence of adverse events Time: Up to 30 days post treatmentOther Outcomes
Description: For each resistance mutation, the agreement of the biopsy result (present, absent, unavailable) and the cfDNA result (present, absent, unavailable) will be assessed at the end of the trial. Agreement of cfDNA and biopsy results will be considered separately for MET amplification and for the gene mutations.
Measure: Biopsy mutation and circulating free deoxyribonucleic acid (cfDNA) mutation results Time: Up to 30 days post treatment