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

NCT ID: NCT04533321

Last Updated: 2020-08-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-30

Study Completion Date

2023-09-30

Brief Summary

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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

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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.

Conditions

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Squamous Cell Carcinoma

Keywords

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MET TP53

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type OTHER

Afatinib

Intervention Type DRUG

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

Interventions

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Afatinib

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

21 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National University Hospital, Singapore

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Boon Cher Goh

Role: PRINCIPAL_INVESTIGATOR

National University Hospital, Singapore

Locations

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National University Hospital

Singapore, , Singapore

Site Status

Countries

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Singapore

Central Contacts

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Boon Cher Goh

Role: CONTACT

Phone: 6779 5555

Email: [email protected]

Facility Contacts

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Boon Cher Goh

Role: primary

References

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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.

Reference Type RESULT
PMID: 22960745 (View on PubMed)

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.

Reference Type RESULT
PMID: 23554766 (View on PubMed)

Other Identifiers

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MC01/02/20

Identifier Type: -

Identifier Source: org_study_id