Evaluating Mutations in MET and TP53 Among Patients Diagnosed With Squamous Cell Carcinoma

• Conditions: Squamous Cell Carcinoma of the Head and Neck; Squamous Cell Carcinoma of the Lung

• Registration Number: NCT03938012
• Lead Sponsor: National University Hospital, Singapore

Brief Summary

This study focuses on advanced lung and head and neck SCC tumours, with adjacent normal lung tissues. Biopsies will be performed in National University Health System, Singapore (NUHS) as part of participants' standard care. Patient blood was also required for extraction of cell free DNA (cfDNA) and genomic DNA (gDNA). Patients' medical records will also be reviewed for the purpose of this study.

Detailed Description

Primary objective:

To investigate the prevalence of MET and TP53 mutations, as well as HER2 and MET amplification, in lung and head and neck tumours, through prospective collection of tumour specimens in newly recruited patients.

Secondary objectives:

1. To distinguish the presence of somatic/germline MET and TP53 mutation in lung and head and neck tumours.

2. To detect for amplifications of MET and/or HER2 genes in SCC samples.

3. To investigate the association and interaction of cMet and HER2 in SCC tumours.

4. To establish a prospective documation of clinical, histopathological, treatment and follow-up (clinic pathological) data of newly recruited patients.

Study Timeline

• Study Start: 2017-10-03
• Study First Submitted: 2019-04-05
• Status Verified: 2019-05
• Study First Submitted QC: 2019-05-01
• Last Update Submitted: 2019-05-01
• Study First Posted: 2019-05-06
• Last Update Posted: 2019-05-06
• Primary Completion: 2021-10
• Study Completion: 2022-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Age 18 years or older
2. Histologic or cytologic confirmation of metastatic squamous cell carcinoma of the lung or head and neck region
3. No other active malignancy within the past 24 months
4. Refractory disease

Exclusion Criteria

1. Patient with other active malignancy within the past 24 months
2. Unable or unwilling to provide signed informed consent

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Identification of MET mutation using digital droplet PCR (ddPCR)	2 years	Germline DNA from the patients will be harvested from whole blood, and the polymorphic MET variant will be determined using ddPCR. Customised probes detecting wildtype MET allele or MET-N375S allele are designed to for genotyping (homozygous/heterozygous).
Identification of TP53 mutation using Sanger sequencing	2 years	DNA from the tumour specimens will be harvested for sequencing to identify cases with somatic mutations of TP53 gene. Changes in codon sequences will be reported.
Presence of MET and HER2 amplification using fluorescence in situ hybridization (FISH)	2 years	FFPE samples retrieved from patients genotyped with MET-N375S polymorphism will be subjected to MET and HER2 testing Abbott PathVysion DNA test kits. Data will be analysed with fluorescence microscopy. HER2 amplification will be defined as gene copies versus chromosome 17 polysomy. MET amplification will be defined as gene copies per nucleus.
Interaction of MET and HER2 receptor tyrosine kinases using proximity ligation assay (PLA)	2 years	PLA will be performed using DUOLINK in situ hybridization. Validation MET and HER2 antibodies will be used for the assay, and signal will be detected with fluorescence microscopy. Detection and quantification of positive signals will determine the presence of MET-HER2 interaction in clinical specimens.
Cell free DNA (cfDNA) will be extracted from patients' plasma to detect for presence of somatic/germline mutation	2 years	Extracted cfDNA will be subjected to ddPCR using designed probes for MET and TP53 mutations. Copies of cfDNA/1mL of plasma will be reported.

Trial Locations

Locations (1)

National University Hospital; 🇸🇬 Singapore, Singapore