Intercalated Combination of Chemotherapy and Tyrosine Kinase Inhibitors as First-line Treatment for Patients With Non-Small-Cell Lung Cancer

Study Overview
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Brief Summary
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Objective: To compare the efficacy and safety of chemotherapy plus intercalated EGFR-tyrosine kinase inhibitors (TKI) combination therapy with TKI alone therapy as first-line treatment for patients with non-small-cell lung cancer (NSCLC). Methods: Patients with untreated, stage IIIB/IV, EGFR mutation-positive NSCLC will be randomly assigned to combination therapy group (receiving four cycles of docetaxel or pemetrexed (on day 1) plus platinum (on day 1) with intercalated TKI (gefitinib, erlotinib or Icotinib, on day 2-15) every 3 weeks) or TKI alone therapy (gefitinib, erlotinib or Icotinib, daily). All patients were continued to receive TKI until progression or unacceptable to toxicity or death. The primary endpoint was progression-free survivial (PFS). Expected results: PFS of combination therapy group will be prolonged to nineteen months while PFS of TKI alone therapy group is ten months. Overall survival (OS) of combination therapy group will be prolonged to 36 months while OS of TKI alone therapy group is 26 months. Hypothesis: Platinum-based chemotherapy plus intercalated TKI combination therapy as first-line treatment will prolong PFS and OS for patients with NSCLC.

Official Title
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Randomised, Controlled Study Comparing Chemotherapy Plus Intercalated EGFR-Tyrosine Kinase Inhibitors Combination Therapy With EGFR-Tyrosine Kinase Inhibitors Alone Therapy as First-line Treatment for Patients With Non-Small-Cell Lung Cancer

Conditions
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Non-Small-Cell Lung Cancer

Intervention / Treatment
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* Drug: Erlotinib
* Drug: Gefitinib
* Drug: Icotinib
* Drug: Docetaxel
* Drug: Pemetrexed
* Drug: Platinum (cisplatin or carboplatin)
* Drug: Erlotinib
* Drug: Gefitinib
* Drug: Icotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, >=18 years of age; Advanced (stage IIIB/IV) non-small-cell lung cancer; Although stageⅠ-ⅢA, have contraindications to surgery; EGFR mutation-positive (EGFR exon-18, exon-19 or exon-21); Measurable disease; ECOG Performance Status 0 or 1 or 2. Exclusion Criteria: Wild-type EGFR; Prior exposure to agents directed at the HER axis; Prior chemotherapy or systemic anti-tumor therapy after advanced disease; Unstable systemic disease; Any other malignancy within last 5 years, except cured basal cell cancer of skin or cured cancer in situ of cervix; Brain metastasis or spinal cord compression.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Combination therapy<br>Interventions: Drug: Erlotinib [Tarceva] or Gefitinib [Iressa] or Icotinib [Conmana] plus Drug: Docetaxel for patients of lung squamous cell carcinoma; Pemetrexed for patients of lung adenocarcinoma plus Drug: Platinum (cisplatin or carboplatin) | Drug: Erlotinib<br>* 150mg po once a day on days 2-15 of each 3 week cycle for 4 cycles; then continue to receive erlotinib150mg po once a day daily until progression<br>* Other names: Tarceva;Drug: Gefitinib<br>* 250mg po once a day on days 2-15 of each 3 week cycle for 4 cycles; then continue to receive gefitinib 250mg po once a day daily until progression<br>* Other names: Iressa;Drug: Icotinib<br>* 125mg po three time a day on days 2-15 of each 3 week cycle for 4 cycles; then continue to receive icotinib 125mg po three time a day daily until progression<br>* Other names: Conmana;Drug: Docetaxel<br>* 75 mg/m2 ivgtt on days 1 of each 3 week cycle for 4 cycles<br>Drug: Pemetrexed<br>* 500 mg/m2 ivgtt on days 1 of each 3 week cycle for 4 cycles<br>Drug: Platinum (cisplatin or carboplatin)<br>* cisplatin -- 75mg/m2 ivgtt on day 1 of each 3 week cycle for 4 cycles or carboplatin -- 5 x AUC ivgtt on day 1 of each 3 week cycle for 4 cycles<br>|
| Other: TKI alone therapy<br>Interventions: Drug: Erlotinib [Tarceva] or Gefitinib [Iressa] or Icotinib [Conmana] | Drug: Erlotinib<br>* 150mg po once a day daily until disease progression<br>* Other names: Tarceva;Drug: Gefitinib<br>* 250mg po once a day daily until disease progression<br>* Other names: Iressa;Drug: Icotinib<br>* 125mg po three times a day daily until disease progression<br>* Other names: Conmana;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Progression-free survival (PFS) is defined to be the time from randomization to progression of disease or death, whichever occurs first. Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate |  | 8 weeks | 
| Duration of response |  | 8 weeks | 
| Time to progression |  | 8 weeks | 
| Overall survival (OS) |  | 8 weeks | 
| Clinical benefit rate |  | 8 weeks | 
| Adverse Events (AEs), Serious Adverse Events (SAEs), laboratory data |  | 4 weeks |