Phase II, open-label, multicenter trial of crizotinib in Japanese patients with advanced non-small cell lung cancer harboring a MET gene alteration: Co-MET study.
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Clinical Trials, Phase II as Topic
Crizotinib
/ administration & dosage
Disease Progression
High-Throughput Nucleotide Sequencing
Humans
Japan
Lung Neoplasms
/ drug therapy
Multicenter Studies as Topic
Mutation
Protein Kinase Inhibitors
/ administration & dosage
Proto-Oncogene Proteins c-met
/ genetics
Crizotinib
MET gene alteration
Next-generation sequencing
Non-small cell lung cancer
RT-PCR assay
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
30 Mar 2020
30 Mar 2020
Historique:
received:
04
12
2019
accepted:
02
03
2020
entrez:
2
4
2020
pubmed:
2
4
2020
medline:
20
1
2021
Statut:
epublish
Résumé
MET-deregulated non-small cell lung cancer represents an urgent clinical need because of the lack of specific therapies. Although recent studies have suggested a potential role for crizotinib in patients harboring MET gene alterations, no conclusive data are currently available. Therefore, we designed the Co-MET study, a single-arm phase II study to assess the efficacy and safety of crizotinib in patients with advanced non-small cell lung cancers harboring MET gene alterations. Co-MET is an open-label, multi-center, single-arm, phase II trial to assess the safety and efficacy of oral crizotinib in patients with advanced non-small cell lung cancer harboring MET exon 14 skipping mutation (cohort 1) or a high MET gene copy number of ≥ 7 (cohort 2). We will identify MET gene alterations using RT-PCR and/or next-generation sequencing. Oral crizotinib 250 mg BID will be administered until disease progression or unacceptable toxicity. A radiology committee will review tumor scans according to the RECIST criteria. The primary endpoint is the objective response rate. Assuming a null hypothesis of 20% objective response rate and an alternative hypothesis of 50% objective response rate for cohort 1, and a one-sided alpha error of 0.05 and 80% power based on the exact binomial distribution, the required number of evaluable patients is 19. We set the exploratory sample size for cohort 2 at 10 patients. The results of this study are expected to provide evidence regarding the usefulness of oral crizotinib for advanced MET exon 14 skipping mutation-positive or MET high gene copy number-positive non-small cell lung cancer. This study was registered with the University Hospital Medical Information Network Clinical Trials Registry as UMIN000031623 on 3 March 2018.
Sections du résumé
BACKGROUND
BACKGROUND
MET-deregulated non-small cell lung cancer represents an urgent clinical need because of the lack of specific therapies. Although recent studies have suggested a potential role for crizotinib in patients harboring MET gene alterations, no conclusive data are currently available. Therefore, we designed the Co-MET study, a single-arm phase II study to assess the efficacy and safety of crizotinib in patients with advanced non-small cell lung cancers harboring MET gene alterations.
METHODS
METHODS
Co-MET is an open-label, multi-center, single-arm, phase II trial to assess the safety and efficacy of oral crizotinib in patients with advanced non-small cell lung cancer harboring MET exon 14 skipping mutation (cohort 1) or a high MET gene copy number of ≥ 7 (cohort 2). We will identify MET gene alterations using RT-PCR and/or next-generation sequencing. Oral crizotinib 250 mg BID will be administered until disease progression or unacceptable toxicity. A radiology committee will review tumor scans according to the RECIST criteria. The primary endpoint is the objective response rate. Assuming a null hypothesis of 20% objective response rate and an alternative hypothesis of 50% objective response rate for cohort 1, and a one-sided alpha error of 0.05 and 80% power based on the exact binomial distribution, the required number of evaluable patients is 19. We set the exploratory sample size for cohort 2 at 10 patients.
DISCUSSION
CONCLUSIONS
The results of this study are expected to provide evidence regarding the usefulness of oral crizotinib for advanced MET exon 14 skipping mutation-positive or MET high gene copy number-positive non-small cell lung cancer.
TRIAL REGISTRATION
BACKGROUND
This study was registered with the University Hospital Medical Information Network Clinical Trials Registry as UMIN000031623 on 3 March 2018.
Identifiants
pubmed: 32228679
doi: 10.1186/s13063-020-4221-7
pii: 10.1186/s13063-020-4221-7
pmc: PMC7104510
doi:
Substances chimiques
Protein Kinase Inhibitors
0
Crizotinib
53AH36668S
MET protein, human
EC 2.7.10.1
Proto-Oncogene Proteins c-met
EC 2.7.10.1
Types de publication
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
298Subventions
Organisme : Practical Research for Innovation Cancer Control from Japan Agency for Medical Research and Development, AMED
ID : JP19ck0106294
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