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

May 1, 2019 updated by: National University Hospital, Singapore
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.

Study Overview

Status

Unknown

Conditions

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 Type

Observational

Enrollment (Anticipated)

80

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Singapore
      • Singapore, Singapore
        • Recruiting
        • National University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification of MET mutation using digital droplet PCR (ddPCR)
Time Frame: 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).
2 years
Identification of TP53 mutation using Sanger sequencing
Time Frame: 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.
2 years
Presence of MET and HER2 amplification using fluorescence in situ hybridization (FISH)
Time Frame: 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.
2 years
Interaction of MET and HER2 receptor tyrosine kinases using proximity ligation assay (PLA)
Time Frame: 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.
2 years
Cell free DNA (cfDNA) will be extracted from patients' plasma to detect for presence of somatic/germline mutation
Time Frame: 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.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National University Hospital, Singapore

Investigators

  • Principal Investigator: Boon Cher Goh, Study Principal Investigator

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 3, 2017

Primary Completion (ANTICIPATED)

October 1, 2021

Study Completion (ANTICIPATED)

October 1, 2022

Study Registration Dates

First Submitted

April 5, 2019

First Submitted That Met QC Criteria

May 1, 2019

First Posted (ACTUAL)

May 6, 2019

Study Record Updates

Last Update Posted (ACTUAL)

May 6, 2019

Last Update Submitted That Met QC Criteria

May 1, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017/00640

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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