Clinical trial NCT03938012: Evaluating Mutations in MET and TP53 Among Patients Diagnosed With Squamous Cell Carcinoma
Official title: Evaluating Mutations in MET and TP53 Among Patients Diagnosed With Squamous Cell Carcinoma
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Squamous Cell Carcinoma of the Lung
Squamous Cell Carcinoma of the Head and Neck
Keywords: mutations in MET and TP53
Lead sponsor: National University Hospital, Singapore
Sponsor class: OTHER
First posted: 2019-05-06
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Identification of MET mutation using digital droplet PCR (ddPCR)
timeFrame: 2 years
measure: Identification of TP53 mutation using Sanger sequencing
timeFrame: 2 years
measure: Presence of MET and HER2 amplification using fluorescence in situ hybridization (FISH)
timeFrame: 2 years
measure: Interaction of MET and HER2 receptor tyrosine kinases using proximity ligation assay (PLA)
timeFrame: 2 years
measure: Cell free DNA (cfDNA) will be extracted from patients' plasma to detect for presence of somatic/germline mutation
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
affiliation: Study Principal Investigator
name: Boon Cher Goh
role: PRINCIPAL_INVESTIGATOR
References:
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, 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.
citation: 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.