To Evaluate the Efficacy of Afatinib in the Treatment of Locally Advanced/Metastatic Non-Small Cell Lung Cancer With NRG1 Fusion

Study Overview
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Brief Summary
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This is an open-label, sing-arm, phase IV clinical study. The study is designed to evaluate the efficacy of Afatinib in treatment of NRG1-fused locally advanced/metastatic non-small cell lung cancer (NSCLC), and explore the clinical factors that may predict the effectiveness of treatment.

Detailed Description
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This is an open-label, sing-arm clinical study,which will recruit about 15 patients in China. The study is designed to evaluate the efficacy of Afatinib in treatment of NRG1-fused locally advanced/metastatic non-small cell lung cancer (NSCLC), and explore the clinical factors that may predict the effectiveness of treatment. Target Patient Population:Locally advanced (stage IIIB) or metastatic (stage IV) NRG1-fused non-small cell lung cancer patients, who have previously received platinum-based doublet chemotherapy and developed disease progression subsequently. Test Drug, Dosage and Medication Regimen:Afatinib is the second-generation TKI drug, which can irreversibly bind to receptors of erbB family. Afatinib will be administered orally at a dose of 40 mg per time, Q.D. If a patient cannot tolerate a dose of 40mg due to adverse reactions, when the adverse reactions restore to level 1 (CTCAE 5.0) or below, the dosage could be adjusted to 30mg per day, Q.D. Evaluations of Study:The data to be collected include demographic characteristics of the patients, information necessary to determine whether the patients are qualified (including medical history, features of previous and current diseases and NRG1 fusion status in tumor tissue), and efficacy and safety data in terms of objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS).

Official Title
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An Open-Labeled, Single-Arm Clinical Study to Evaluate the Efficacy of Afatinib in Treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer With NRG1-Fusion

Conditions
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NRG1-fused Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Afatinib Dimaleate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient or his/her legal representative has signed a written informed consent form and dated it prior to any specific research procedure. Aged 18 years or older. Locally advanced or metastatic non-small cell lung cancer with NRG1 fusion detected by DNA or RNA-based next-generation sequencing (NGS) technology in tumor tissue specimens or liquid specimens. The patient has received platinum-based doublet chemotherapy previously. ECOG performance status score is 0 2. The patient has sufficient bone marrow and organ functionality, which can be proved by complete blood cell count, blood biochemistry and urine biochemistry tests at baseline. The patient has measurable lesion(s). The female patient of childbearing age must adopt appropriate contraceptive measures and are not allowed to breastfeed a child. The male patient must voluntarily use contraceptives. Exclusion Criteria: The patient has shown any severe or uncontrollable systemic disease sign that the investigators believe may significantly change the risk/benefit balance of the patient, including uncontrollable hypertension, high active bleeding tendency, active infection or significant damage of bone marrow or other functions. The patient has previously been treated with EGFR-TKI or any monoclonal antibody that acts on HER2/3. The patient has been found with symptomatic metastatic tumor of central nervous system (CNS). The patient has a history of interstitial pneumonia or radiation pneumonia requiring steroid therapy. The patient has not recovered yet from toxic reactions with CTCAE grade ≥3 (CTCAE5.0) caused by previous treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Afatinib treatment group<br>This is an open-label, sing-arm phase IV clinical study | Drug: Afatinib Dimaleate<br>* Afatinib is the second-generation TKI drug, which can irreversibly bind to receptors of erbB family. Afatinib will be administered orally at a dose of 40 mg per time, Q.D. If a patient cannot tolerate a dose of 40mg due to adverse reactions, when the adverse reactions restore to level 1 (CTCAE 5.0) or below, the dosage could be adjusted to 30mg per day, Q.D.<br>* Other names: GIOTRIF®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate (ORR) | ORR | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease control rate (DCR) | DCR | Up to 12 months | 
| progression-free survival (PFS) | PFS | Up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally advanced (stage IIIB) or metastatic (stage IV), have previously received platinum-based doublet chemotherapy and developed disease progression subsequently