Central Nervous System(CNS) Efficacy of Dacomitinib

Study Overview
=================
Brief Summary
-----------------
This is a single-arm, phase II study of dacomitinib in advanced EGFR-mutant NSCLC patients who have non-irradiated brain metastasis.

Official Title
-----------------
A Phase II Study of Dacomitinib in Advanced Epidermal Growth Factor Receptor (EGFR)-Mutant Non-small Cell Lung Cancer (NSCLC) Patients Who Have Non-irradiated Brain Metastasis

Conditions
-----------------
Non Small Cell Lung Cancer, Brain Metastases

Intervention / Treatment
-----------------
* Drug: Dacomitinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Biopsy proven recurrent or metastatic NSCLC (adenocarcinoma) with major EGFR mutation (exon 19 deletion or Leu858Arg mutation without the Thr790Met) No prior systemic treatment of advanced NSCLC (Neoadjuvant or adjuvant chemotherapy are allowed, without limitation on its treatment timing) Age ≥20 years Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 Had at least one measurable intracranial lesion as ≥ 5mm in the longest diameter by magnetic resonance imaging (MRI) (≥ 5mm by thin section (1.2mm) of brain MRI image, ≥ 10mm by less thin section(2.5mm) brain MRI ), which checked within 4 weeks before enrollment. If MRI slice thickness is not appropriate, we need to recheck Brain MRI Number of brain metastasis =>5 Adequate organ function Female subjects must either be of non-reproductive potential Subject is willing and able to comply with the protocol Signed written informed consent Exclusion Criteria: Severe symptomatic brain metastasis, needing urgent control with radiotherapy or high dose steroid: the definition of high dose steroid is the equivalent dose of dexamethasone 10 mg or higher per day (mild symptoms controlled with low dose of steroid can be enrolled) With leptomeningeal seeding Exposure to EGFR-TKIs or other EGFR targeting agents at any time in either neoadjuvant or adjuvant setting Local treatment (stereotatic radiosurgery or whole brain radiotherapy) for brain metastases Uncontrolled systemic illness including uncontrolled hypertension, active bleeding, or active infection. Past medical history of interstitial lung disease, drug induced interstitial lung disease, radiation pneumonitis which required steroid treatment Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study arm<br>Dacomitinib | Drug: Dacomitinib<br>* Secondary generation EGFR-tyrosine kinase inhibitor (TKI) (Dacomitinib) for EGFR mutant NSCLC patients with non irradiated brain metastasis<br>* Other names: Vizimpro;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CNS objective response rate (Complete response or Partial response) | The rate of CR or PR of CNS disease | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CNS progression-free survival | Time from enrollment to CNS progression or death | 1 year | 
| Cumulative incidence of CNS failure by competing risk analysis | To evaluate the CNS efficacy of dacomitinib | 1 year | 
| Extracranial objective response rate | The rate of CR or PR | 1 year | 
| Progression-free survival | Time from enrollment to progression or death | 1 year | 
| Overall survival | Time from enrollment to death of any cause | 1 year | 
| Safety by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 | The % of side effect | 1 year |