EGFR Mutation Positive NSCLC Patients With Gefitinib and Thalidomide

Study Overview
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Brief Summary
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EGFR-TKIs are the standard first-line treatment option for EGFR-mutant NSCLC. After a randomized phase II trial, JO25567 was presented at 2014 ASCO, the synergistic effect of progression-free survival(PFS) could be expected when EGFR TKI, Gefitinib is combined with Antiangiogenesis agent thalidomide, Therefore Chinese data of treating EGFR mutation positive NSCLC patients with Gefitinib and thalidomide is significantly necessary for developing new standard treatment in first-line therapy in Chinese EGFR mutant NSCLC patients. In this study, The investigators will investigate the efficacy and safety of Gefitinib and thalidomide combination compare to Gefitinib alone in Chinese EGFR-mutant NSCLC patients.

Detailed Description
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EGFR-TKIs are the standard first-line treatment option for EGFR-mutant NSCLC. After a randomized phase II trial, JO25567 was presented at 2014 ASCO, the synergistic effect of progression-free survival(PFS) could be expected when EGFR TKI, Gefitinib is combined with Antiangiogenesis agent thalidomide, . Even Chinese and Japanese are classified as Asian based on location, the figure of Chinese is more tended to Western people due to the dietary life in recent years. However the incidence rate of EGFR mutation positive patients in Chinese is much higher than Western countries. Therefore Chinese data of treating EGFR mutation positive NSCLC patients with Gefitinib and thalidomide is significantly necessary for developing new standard treatment in first-line therapy in Chinese EGFR mutant NSCLC patients. In this study, The investigators will investigate the efficacy and safety of Gefitinib and thalidomide combination compare to Gefitinib alone in Chinese EGFR-mutant NSCLC patients.

Official Title
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A Randomized Phase II Study of Gefitinib Alone Versus Gefitinib Plus Thalidomide for Advanced Non-small Cell Lung Cancer With Epidermal Growth Factor Receptor Activating Mutations

Conditions
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NSCLC Stage IV, Chemotherapy Effect

Intervention / Treatment
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* Drug: Thalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed stage IIIB & IV non-small cell lung cancer other than squamous cell carcinoma Patients with one or more measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1) Locally diagnosed sensitive EGFR mutation positive (Exon 19 deletion or L858R) ECOG performance 0 1 Age ≥ 19 years and - No previous treatment Adequate organ function by following: ANC ≥1,500/uL, hemoglobin ≥9.0g/dL, platelet ≥100,000/uL Serum bilirubin < 1 x UNL, AST (SGOT) and ALT (SGPT) < 2.5 x UNL, If Liver metastasis, Serum bilirubin < 3 x UNL, AST (SGOT) and ALT (SGPT) < 5 x UNL Serum Cr ≤ 1 x UNL Patients who have had undergone radiotherapy are acceptable if patients meet all of the following criteria: No history of irradiation to pulmonary tumor lesions. In case of palliative irradiation to bone lesions in lung: at least 12 weeks must have passed at the date of registration since the last irradiation of the sites. In case of irradiation to non-pulmonary sites: at least two weeks must have passed at the date of inclusion since the last irradiation of the sites At the time of registration, at least the following period has passed since last date of the prior therapy or procedure: Surgery(including exploratory/ examination thoracotomy): 4 weeks Pleural cavity drainage: 1 weeks Pleurodesis without anti-neoplastic agents (inclusive of BRM such as Picibanil): 2 week Biopsy accompanied by incision (including thoracoscopic biopsy): 2 week Procedure for trauma (exclusive of patients with unhealed wound): 2 weeks Transfusion of blood, preparation of hematopoietic factor: 2 week Puncture and aspiration cytology: 1 week Other investigational product: 4 weeks Written informed consent form Exclusion Criteria: • Previous history of malignancy within 3 years from study entry except treated non-melanomatous skin cancer, uterine cervical cancer in situ, or thyroid cancer Prior chemotherapy or systemic anti-cancer therapy for metastatic disease but postoperative adjuvant or neoadjuvant therapy of 6 months or more previously is allowed Patients who received previous treatment for lung cancer with drugs Symptomatic or uncontrolled central nervous system (CNS) metastases Patients with increased risk of bleeding, clinically significant cardiovascular diseases, a history of thrombosis or thromboembolism in the 6 months prior to treatment, gastrointestinal problems, and neurologic problems Any significant ophthalmologic abnormality Pre-existing parenchymal lung disease such as pulmonary fibrosis Known allergic history of Erlotinib or Bevacizumab Interstitial lung disease or fibrosis on chest radiogram Active infection, uncontrolled systemic disease (cardiopulmonary insufficiency, fatal arrhythmias, hepatitis) Pregnant or nursing women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gefitinib 250mg qd thalidomide 200mg qn<br> | Drug: Thalidomide<br>* Gefitinib 250mg Thalidomide 200 MG<br>|
| Active Comparator: Gefitinib 250mg qd<br> | Drug: Thalidomide<br>* Gefitinib 250mg Thalidomide 200 MG<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | progression-free survival | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to at least 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Overall Response Rate | through study completion, and average of 2 years | 
| OS | Overall Survival | From date of randomization until the date of death or date of last visit/contact, whichever came first, assessed to at least 36 months |