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

NCT03938012 | Unknown DMC

• 1 other identifier: 2017/00640
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Squamous Cell Carcinoma of the Lung; Squamous Cell Carcinoma of the Head and Neck

Keywords

mutations in MET and TP53

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• 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

Study Arms (1)

Lung and head and neck tumours

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

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study intend to recruit a total of 80 patients over 2 years. Written informed consent will be requested from every patient prior to enrollment into the study. All eligibility criteria and consent form must be met before tumour DNA and plasma DNA from patients can be processed.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, Singapore

RECRUITING

Related Publications (2)

• 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, Cortes ML, Auclair D, Berger MF, Saksena G, Guiducci C, Onofrio RC, Parkin M, Romkes M, Weissfeld JL, Seethala RR, Wang L, Rangel-Escareno C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Winckler W, Ardlie K, Gabriel SB, Meyerson M, Lander ES, Getz G, Golub TR, Garraway LA, Grandis JR. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011 Aug 26;333(6046):1157-60. doi: 10.1126/science.1208130. Epub 2011 Jul 28.

  PMID: 21798893 RESULT

• 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.

  PMID: 22960745 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Patient blood was also required for extraction of cell free DNA (cfDNA) and genomic DNA (gDNA).

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Boon Cher Goh

  Study Principal Investigator

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Boon Cher Goh

CONTACT

6779 5555; phcgbc@nus.edu.sg

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2019
• First Posted: May 6, 2019
• Study Start: October 3, 2017
• Primary Completion: October 1, 2021
• Study Completion: October 1, 2022
• Last Updated: May 6, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)