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

Squamous Cell Carcinoma of the Head and Neck Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03938012
• Other study ID #: 2017/00640
• Status: Recruiting
• Start date: October 3, 2017
• Est. completion date: October 2022

Study information

• Verified date: May 2019
• Source: National University Hospital, Singapore
• Contact: Boon Cher Goh
• Phone: 6779 5555
• Email: phcgbc[@]nus.edu.sg
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: October 2022
• Est. primary completion date: October 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Lung Neoplasms
• Squamous Cell Carcinoma of Head and Neck
• Squamous Cell Carcinoma of the Head and Neck
• Squamous Cell Carcinoma of the Lung

Locations

Country	Name	City	State
Singapore	National University Hospital	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
National University Hospital, Singapore

Country where clinical trial is conducted

Singapore, 

References & Publications (2)

Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012 Sep 27;489(7417):519-25. doi: 10.1038/nature11404. Epub 2012 Sep 9. Erratum in: Nature. 2012 Nov 8;491(7423):288. Rogers, Kristen [cor — View Citation

Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, Kryukov GV, Lawrence MS, Sougnez C, McKenna A, Shefler E, Ramos AH, Stojanov P, Carter SL, Voet D, Cortés ML, Auclair D, Berger MF, Saksena G, Guiducci C, Onofrio RC, Parkin M, Romkes — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of MET mutation using digital droplet PCR (ddPCR)	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).	2 years
Primary	Identification of TP53 mutation using Sanger sequencing	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.	2 years
Primary	Presence of MET and HER2 amplification using fluorescence in situ hybridization (FISH)	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.	2 years
Primary	Interaction of MET and HER2 receptor tyrosine kinases using proximity ligation assay (PLA)	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.	2 years
Primary	Cell free DNA (cfDNA) will be extracted from patients' plasma to detect for presence of somatic/germline mutation	Extracted cfDNA will be subjected to ddPCR using designed probes for MET and TP53 mutations. Copies of cfDNA/1mL of plasma will be reported.	2 years