A Biomarker-implemented Clinical Study Evaluating Mutations in MET and TP53 in a Population of Treatment-refractory Squamous Cell Carcinoma
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|ClinicalTrials.gov Identifier: NCT04533321|
Recruitment Status : Not yet recruiting
First Posted : August 31, 2020
Last Update Posted : August 31, 2020
|Condition or disease||Intervention/treatment||Phase|
|Squamous Cell Carcinoma||Drug: Afatinib||Phase 2|
- To determine the efficacy of afatinib in patients with germline MET-N375S polymorphism.
- To determine the tolerability of afatinib in chemo-relapsed patients with germline MET-N375S polymorphism.
- 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.
- To establish tumour cell lines, spheroids of xenografts for drug screening.
Endpoints of study:
- To determine the response rate of SCC HN/lung with Met-N375S to afatinib.
- The secondary endpoints include progression-free survival and toxicity.
- Frequency of MET mutations and TP53 mutations in patients with cancer.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Biomarker-implemented Clinical Study Evaluating Mutations in MET and TP53 in a Population of Treatment-refractory Squamous Cell Carcinoma|
|Estimated Study Start Date :||September 2020|
|Estimated Primary Completion Date :||September 2023|
|Estimated Study Completion Date :||September 2023|
Patients genotyped positive for MET-N375S polymorphism
will be treated with orally administered daily dose of afatinib (Gilotrif®) in a fasting state (1 hour before or 2 hours after meals).
Afatinib is approved therapy for SCC of the lung after progression with standard of care chemotherapy.
- p-HER2 and p-MET status [ Time Frame: 3 years ]using immunohistochemistry.
- MET-N375S mRNA copy number [ Time Frame: 3 years ]using RNAscope staining.
- Identification of MET and TP53 mutations using droplet digital PCR (ddPCR) and Sanger sequencing. [ Time Frame: 3 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.
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).
- Presence of MET and HER2 amplification using fluorescence in situ hybridization (FISH) [ Time Frame: 3 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 cMet and HER2 receptor tyrosine kinases using proximity ligation assay (PLA) [ Time Frame: 3 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04533321
|Contact: Boon Cher Goh||6779 5555||Boon_Cher_Goh@nuhs.com.sg|
|National University Hospital|
|Contact: Boon Cher Goh 65-6772-4617 Boon_Cher_Goh@nuhs.com.sg|
|Principal Investigator:||Boon Cher Goh||National University Hospital, Singapore|