Clinical Trials /

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

NCT04533321

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: MC01/02/20
  • NCT ID: NCT04533321

Conditions

  • Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
AfatinibPatients genotyped positive for MET-N375S polymorphism

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
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).
  • Afatinib

Eligibility Criteria

        Inclusion Criteria:

          -  Patients may be included in the study only if they meet all of the following 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, and has failed standard treatment.

               3. No other active malignancy within the past 24 months

               4. All subjects must have at least one tumour lesion (primary or metastatic) that is
                  suitable for free-hand or image-guided biopsy at baseline.

               5. Clinical study will enroll patients genotyped positive for MET-N375S
                  polymorphism.

               6. Eastern Cooperative Oncology Group (ECOG) performance status < 2

               7. Adequate organ function as defined by:

                  a. 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

               8. Capable of swallowing tablets

               9. 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.

              10. Signed informed consent obtained before any study specific procedure. Subjects
                  must be able to understand and be willing to sign the written informed consent.

        Exclusion Criteria:

          -  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
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:21 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:p-HER2 and p-MET status
Time Frame:3 years
Safety Issue:
Description:using immunohistochemistry.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:National University Hospital, Singapore

Trial Keywords

  • MET
  • TP53

Last Updated

August 26, 2020