Squamous Cell Carcinoma of the LungNCT03938012
Evaluating Mutations in MET and TP53 Among Patients Diagnosed With Squamous Cell Carcinoma
An observational study of Squamous Cell Carcinoma of the Lung and Squamous Cell Carcinoma of the Head and Neck, run by National University Hospital, Singapore at 1 site in Singapore.
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). Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Squamous Cell Carcinoma of the Lung, Squamous Cell Carcinoma of the Head and Neck
- How many people
- 80 participants
- Where
- 1 siteSingapore
- Study dates
- 3 Oct 2017to Oct 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- Patient with other active malignancy within the past 24 months
- Unable or unwilling to provide signed informed consent
Trial locations and contacts
1 site in 1 country.
Singapore1 site, 1 recruiting
- Recruiting
National University Hospital
Singapore
Boon Cher Goh, MBBS, MRCP, 65-6772-4617, Boon_Cher_Goh@nuhs.com.sg
About this study
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.
Read the 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:
- To distinguish the presence of somatic/germline MET and TP53 mutation in lung and head and neck tumours.
- To detect for amplifications of MET and/or HER2 genes in SCC samples.
- To investigate the association and interaction of cMet and HER2 in SCC tumours.
- To establish a prospective documation of clinical, histopathological, treatment and follow-up (clinic pathological) data of newly recruited patients.
- Keywords
- mutations in MET and TP53
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2019
- Study start3 Oct 2017
- Primary completionOct 2021 (estimated)
- Study completionOct 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Squamous Cell Carcinoma of the LungStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Boon Cher Goh, Principal investigator, Study Principal Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03938012
- Sponsor's protocol ID
- 2017/00640
- Other IDs
- 2017
- Status last verified
- May 2019
- First submitted
- 5 Apr 2019
- Last updated
- 6 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 21798893Cancer 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.
PubMed 22960745
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating Mutations in MET and TP53 Among Patients Diagnosed With Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT03938012
- Acronym / sponsor ID
- 2017/00640
- Keywords
- mutations in MET and TP53
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- 3 Oct 2017 (actual)
- Primary completion
- Oct 2021 (estimated)
- Study completion
- Oct 2022 (estimated)
- First posted
- 6 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To distinguish the presence of somatic/germline MET and TP53 mutation in lung and head and neck tumours.
- To detect for amplifications of MET and/or HER2 genes in SCC samples.
- To investigate the association and interaction of cMet and HER2 in SCC tumours.
- To establish a prospective documation of clinical, histopathological, treatment and follow-up (clinic pathological) data of newly recruited patients.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (2 listed)
- Patient with other active malignancy within the past 24 months
- Unable or unwilling to provide signed informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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).
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.
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.
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.
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2019.
- Results publication: PubMed 21798893Stransky 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.
- Results publication: PubMed 22960745Cancer 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boon Cher Goh principal investigator
Study Principal Investigator
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Squamous Cell Carcinoma of the Lung and Squamous Cell Carcinoma of the Head and Neck, run by National University Hospital, Singapore at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Boon Cher Goh (6779 5555, phcgbc@nus.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of MET mutation using digital droplet PCR (ddPCR) (time frame: 2 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03938012, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2019.