Icotinib as Neoadjuvant and Adjuvant Therapy in EGFR-mutant Stage IIIB or Oligometastasis Non-small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is to evaluate the pulmonary and metastases lesions objective response rate after Icotinib preoperative therapy in EGFR-mutant stage IIIB or oligometastasis Non-small Cell Lung Cancer which can be potentially radical treated by surgery.

Detailed Description
-----------------
Patients with EGFR-mutant stage IIIB or oligometastasis Non-small Cell Lung Cancer which can be potentially radical treated by surgery are arranged to receive Icotinib with a dose of 125 mg three times per day orally for 8 weeks as neoadjuvant therapy; then they receive surgical resection of the tumor. If there is curative effect of Icotinib according to the RECIST or pathological report, the patients will continue receive Icotinib for two years as adjuvant therapy after surgery or till progressive disease or unaccepted toxicity. The primary objective of this study is evaluate the pulmonary and metastases lesions objective response rate after Icotinib preoperative therapy.

Official Title
-----------------
Icotinib as Neoadjuvant and Adjuvant Therapy in EGFR-mutant Stage IIIB or Oligometastasis Non-small Cell Lung Cancer: a Single Arm, Phase II Clinical Study

Conditions
-----------------
EGF-R Positive Non-Small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: Icotinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histology or cytology confirmed Non-small Cell Lung Cancer; EGFR mutation (EGFR 19del and/or 21L858R) detected by tumor tissue biopsy of primary lesion or metastatic lesion or plasma ctDNA No previous anti-tumor treatment such as surgery, chemotherapy, radiotherapy or biological therapy Stage IIIB or IV Oligometastasis Non-small Cell Lung Cancer. (a) stage IV Oligometastasis: the metastasis organ mainly include: 1. adrenal metastasis which can be potentially resected by surgery or radically treated by SRS radiotherapy; 2. brain metastasis which can be potentially resected by surgery or radically treated by SRS radiotherapy. At the same time, the primary lesion of the lung can be completely removed, which should be T1-2, N0-1 or T3, N0. (b) stage IIIB (T1-3, N3): it is limited to patients who are unsuitable or refuse to accept pulmonary primary lesion radiotherapy. It only include subclavian lymph node or anterior scalenus lymph node metastasis (mediastinal lymph node metastasis is excluded by PET-CT). The metastasis lesion should be single or less than 3, its diameter is no more than 3 cm and can be potentially resected. Sufficient tumor histological specimens (non-cytology) for molecular marker analysis At least one lesion with measurable diameter and its longest diameter is large than 10 mm by CT measurement Exclusion Criteria: Previous systemic anti-tumor treatment of Non-small Cell Lung Cancer, including cytotoxic drug therapy, targeted drug therapy (tyrosine kinase inhibitors or monoclonal antibodies) and experimental treatment, etc Previous local radiotherapy of Non-small Cell Lung Cancer Be allergic to any component of Icotinib tablet (Conmana) Other cancers within five years prior to the treatment of this study. Except for cervical carcinoma, basal cell carcinoma and bladder epithelial neoplasm (including Ta and Tis) Any instable systemic disease, including: active infection, high blood pressure out of control, unstable angina, onset of angina pectoris within the past 3 months, congestive heart failure, myocardial infarction, severe arrhythmia, liver, kidney or metabolic disease Previous interstitial lung disease, drug-induced interstitial disease, radiation pneumonia requiring hormone therapy or any active intersexual lung disease with clinical evidence Idiopathic pulmonary fibrosis detected by CT scan at baseline; Not fully controlled eye inflammation or infections, or any condition that may lead to the above eye diseases Human immunodeficiency virus infection Patients undergoing major surgery or severe trauma within 2 months prior to the first use of the experimental drug Patients with Small Cell Lung Cancer Pregnant or lactating women Neurological or psychiatric disorders history, including epilepsy or dementia Other situations not appropriate to enter the group considering by the investigators

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 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: Icotinib<br>Patients with EGFR-mutant stage IIIB or oligometastasis Non-small Cell Lung Cancer which can be potentially radical treated by surgery are arranged to receive Icotinib with a dose of 125 mg three times per day orally for 8 weeks before surgery and 2 years as adjuvant therapy after surgery or till progressive disease or unaccepted toxicity. | Drug: Icotinib<br>* Patients with EGFR-mutant stage IIIB or oligometastasis Non-small Cell Lung Cancer which can be potentially radical treated by surgery are arranged to receive Icotinib with a dose of 125 mg three times per day by mouth for 8 weeks as neoadjuvant therapy before surgery and 2 years as adjuvant therapy or till progressive disease or unaccepted toxicity.<br>* Other names: Conmana;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate as assessed by RECIST1.1 | Objective Response Rate was defined as the percentage of participants whose tumor lesions disappear completely or diameters reduced by at least 30% as assessed by RECIST1.1. | eight weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate as assessed by RECIST1.1 | Disease Control Rate was defined as the total percentage of participants except for those with tumor lesions diameters increased by at least 20% as assessed by RECIST1.1. | five years after surgery | 
| Time to Tumor Progression as assessed by RECIST1.1 | Time to Tumor Progression was defined as the time between participants' randomization and their tumor progression as assessed by RECIST1.1. | five years after surgery | 
| Overall survival of participants | Overall survival was defined as the time from participants' randomization to their death due to any cause. | five years after surgery | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | The number of participants with treatment-related adverse events as assessed by CTCAE v4.0 would be recorded and calculated after them participating into the study and taking the experimental drug. | five years after surgery |