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Squamous Cell CarcinomaPhase 2NCT04533321

A Biomarker-implemented Clinical Study Evaluating Mutations in MET and TP53 in a Population of Treatment-refractory Squamous Cell Carcinoma

A Phase 2 study testing Afatinib in people with Squamous Cell Carcinoma, run by National University Hospital, Singapore at 1 site in Singapore.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Afatinib is approved therapy for SCC of the lung after progression with standard of care chemotherapy. There is also evidence of improvement of progression free survival of patients with metastatic/recurrent SCC of the head and neck after failure of chemotherapy in patients treated with afatinib. Read more about this study

Who is it for?
Ages 21 to 99 years
Conditions the study is for
Squamous Cell Carcinoma
What is being tested?
Afatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteSingapore
Study dates
Sep 2020to Sep 2023
Phase
Phase 2
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 21 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients may be included in the study only if they meet all of the following criteria:
  • Age 18 years or older
  • Histologic or cytologic confirmation of metastatic squamous cell carcinoma of the lung or head and neck region, and has failed standard treatment.
  • No other active malignancy within the past 24 months
  • All subjects must have at least one tumour lesion (primary or metastatic) that is suitable for free-hand or image-guided biopsy at baseline.
  • Clinical study will enroll patients genotyped positive for MET-N375S polymorphism.
Show all 12Show fewer
  • Eastern Cooperative Oncology Group (ECOG) performance status < 2
  • Adequate organ function as defined by:
  • Bone marrow function i. Haemoglobin ≥ 9g/dl ii. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L iii. Platelet count ≥ 75 x 109/L. b. Liver function i. Bilirubin < 2.5x upper limit of normal (ULN) ii. Alanine transaminase (ALT) and aspartate transaminase (AST) < 2.5x ULN or < 5x ULN if liver metastases are present iii. Prothrombin time (PT) within the normal range for the institution. c. Renal function i. Plasma creatinine <1.5x institutional ULN
  • Capable of swallowing tablets
  • Recovery from any previous drug- or procedure-related toxicity to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 Grade 0 or 1 (except alopecia), or to baseline preceding the prior treatment.
  • Signed informed consent obtained before any study specific procedure. Subjects must be able to understand and be willing to sign the written informed consent.

Who cannot join

  • 1. Chemotherapy, radiotherapy, surgery, immunotherapy or other therapy within 3 weeks of starting investigational medicinal product (IMP).
  • 2. Pregnancy or breastfeeding. 3. Women of childbearing potential not employing adequate contraception. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of study medication, and a negative result must be documented before start of study medication. Women of childbearing potential and men, must agree to use adequate contraception (barrier method of birth control) upon signing the informed consent form until at least 3 months after the last study drug administration 4. Known or suspected allergy to the investigational agent or any agent given in association with this study.
  • 5. Concurrent cancer which is distinct in primary site or histology from the cancer being evaluated in this study 6. Patients with CTCAE Grade 2 or higher peripheral neuropathy. 7. History of significant cardiac disease: congestive cardiac failure > NYHA class II, ongoing unstable angina, new-onset angina or myocardial infarction within the past 3 months

Trial locations and contacts

1 site in 1 country.

Boon Cher Goh contact

6779 5555

Boon_Cher_Goh@nuhs.com.sg

Singapore1 site

  • National University Hospital

    Singapore

    Boon Cher Goh, 65-6772-4617, Boon_Cher_Goh@nuhs.com.sg

Other trials in Singapore

About this study

Afatinib is approved therapy for SCC of the lung after progression with standard of care chemotherapy. There is also evidence of improvement of progression free survival of patients with metastatic/recurrent SCC of the head and neck after failure of chemotherapy in patients treated with afatinib. Therefore, treatment of patients with these 2 conditions with afatinib is not experimental, and will follow conventional clinical management.

Read the detailed description

Clinical objectives:

  1. To determine the efficacy of afatinib in patients with germline MET-N375S polymorphism.
  2. To determine the tolerability of afatinib in chemo-relapsed patients with germline MET-N375S polymorphism.

Research objectives:

  1. To determine the prevalence of MET and TP53 mutations, as well as HER2 and MET amplification, in various cancers, particularly head and neck cancers and lung cancers.
  2. To establish tumour cell lines, spheroids of xenografts for drug screening.

Endpoints of study:

  1. To determine the response rate of SCC HN/lung with Met-N375S to afatinib.
  2. The secondary endpoints include progression-free survival and toxicity.
  3. Frequency of MET mutations and TP53 mutations in patients with cancer.
Being tested
Afatinib
Keywords
MET, TP53
Medical subject headings
Carcinoma, Squamous Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AfatinibDrug

    Afatinib is approved therapy for SCC of the lung after progression with standard of care chemotherapy.

Study groups in NCT04533321
Study groupRoleWhat they receive
Patients genotyped positive for MET-N375S polymorphismOtherwill be treated with orally administered daily dose of afatinib (Gilotrif®) in a fasting state (1 hour before or 2 hours after meals).
Receives: Drug: Afatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. p-HER2 and p-MET status

    using immunohistochemistry.

    Measured: 3 years

  2. MET-N375S mRNA copy number

    using RNAscope staining.

    Measured: 3 years

  3. Identification of MET and TP53 mutations using droplet digital PCR (ddPCR) and 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.

    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: 3 years

  4. 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: 3 years

  5. Interaction of cMet 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: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2020
  2. Study startSep 2020 (estimated)
  3. Primary completionSep 2023 (estimated)
  4. Study completionSep 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04533321
Sponsor's protocol ID
MC01/02/20
Status last verified
Aug 2020
First submitted
26 Aug 2020
Last updated
31 Aug 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 22960745

  • Liu Y, Zhang Q, Ren C, Ding Y, Jin G, Hu Z, Xu Y, Shen H. A germline variant N375S in MET and gastric cancer susceptibility in a Chinese population. J Biomed Res. 2012 Sep;26(5):315-8. doi: 10.7555/JBR.26.20110087. Epub 2012 Mar 29.

    PubMed 23554766

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Afatinib in people with Squamous Cell Carcinoma, 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 12 inclusion and 3 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 31 Aug 2020. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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, Boon_Cher_Goh@nuhs.com.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

p-HER2 and p-MET status (time frame: 3 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 NCT04533321, 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 31 Aug 2020.

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