SNPMiner Trials (Home Page)
Report for Mutation L1198F
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There is one clinical trial.
Clinical Trials
1 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
Patients with an ALK L1198F mutation alone or with another mutation, and patients with high level MET amplification receive crizotinib PO BID. --- L1198F ---
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