Study of Chemotherapy Sequenced by or Combined With EGFR-TKIs for NSCLC Patients Failed to EGFR-TKIs Therapy

Study Overview
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Brief Summary
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There are two different treatment modes for NSCLC patients who failed to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) after initially responding to EGFR-TKI. One is EGFR-TKI combined with chemotherapy and the other is chemotherapy followed by EGFR-TKI. It is unclear which one is more suitable to this group of lung cancer patients. So this phase Ⅱclinical trial is designed to compare the efficiency and safety of these two different treatment modes.

Detailed Description
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Responses to EGFR-TKIs are quiet dramatic and durable, especially in patients with EGFR gene classic mutations, such as 19 deletion or 21 leucine 858 arginine(L858R). However, most patients with NSCLC who respond to EGFR-TKIs eventually experience progression of disease after approximately 12 months. The lack of an established therapeutic option for NSCLC patients who have progressive disease after EGFR-TKIs failure poses a great challenge to physicians in terms of how best to manage this growing group of lung cancer patients. In clinical practice some of the initially EGFR-TKI sensitive tumors which progressed evidence a striking increase in tumor volume within several weeks, after being taken off EGFR-TKI. This response is called rebound phenomenon. Most experts still believe that these tumors continue to be oncogene-addicted to EGFR. So it is rational that EGFR-TKI combined with another chemotherapy regimen can be used to treat NSCLC after the failure of EGFR-TKI therapy. However in some phase Ⅱclinical trials involved a few NSCLC patients who failed to EGFR-TKI therapy, another treatment mode, that is to say, at least one cytotoxic chemotherapy was used firstly then switched to EGFR-TKI therapy until progression of disease, was used and called reintroduction or retreatment of EGFR-TKI. Using this treatment mode, some investigators reported the partial remission (PR) and disease control rate (DCR) were observed in 21.7%-36% and 65.2%-86% NSCLC patients.

Official Title
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A Phase Ⅱ Randomized Controlled Trial to Compare Chemotherapy Sequenced by EGFR-TKIs and Chemotherapy Combined With EGFR-TKIs for Advanced or Metastatic NSCLC Patients Failed to EGFR-TKIs Therapy

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: combined group
* Drug: Sequenced group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥ 18 years histologically and cytologically proven non-small cell bronchogenic carcinoma (sputum cytology alone was not acceptable) clinical stages ⅢB or Ⅳ recurrent or refractory disease following previous first-line chemotherapy regimens containing platinum and second-line EGFR-TKIs therapy partial remission (PR) or stable disease (SD) at least for 6 months during previous EGFR-TKI treatment at least one bidimensionally measurable or radiographically assessable lesion Eastern cooperative oncology group performance status (ECOG PS) ≤ 2 life expectancy ≥ 12 weeks adequate hematological, renal, and hepatic functions Exclusion Criteria: additional malignancies uncontrolled systemic disease any evidence of clinically active interstitial lung disease newly diagnosed central nervous system (CNS) metastasis and not treated by radiotherapy or surgery pregnancy or breast feeding phase

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Other: combined group<br>combined group chemotherapy with docetaxel 75mg/m2 d1 or pemetrexed 500mg/m2 d1, every 3 weeks,at least 2 cycles and the maximal cycle is 6 depending on disease evaluation and patient's physical condition combined with gefitinib 250mg once per day from the start day of chemotherapy until disease progression or intolerable side effects. | Drug: combined group<br>* chemotherapy with docetaxel 75mg/m2 d1 or pemetrexed 500mg/m2 d1, every 3 weeks,at least 2 cycles and the maximal cycle is 6 depending on disease evaluation and patient's physical condition combined with gefitinib 250mg once per day from the start day of chemotherapy until disease progression or intolerable side effects.<br>* Other names: Gefitinib (Iressa);|
| Other: sequenced group<br>sequenced group chemotherapy with docetaxel 75mg/m2 d1 or pemetrexed 500mg/m2 d1, every 3 weeks,at least 2 cycles and the maximal cycles is 6 depending on disease evaluation or patient's physical condition sequenced by gefitinib 250mg once per day until disease progression or intolerable side effects. | Drug: Sequenced group<br>* sequenced group chemotherapy with docetaxel 75mg/m2 d1 or pemetrexed 500mg/m2 d1, every 3 weeks,at least 2 cycles and the maximal cycles is 6 depending on disease evaluation or patient's physical condition sequenced by gefitinib 250mg once per day until disease progression or intolerable side effects.<br>* Other names: Gefitinib (Iressa);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 52 weeks. | up to 52 weeks (about one year) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | From date of randomization until the date of death from any cause, assessed up to 100 weeks. | up to 100 weeks | 
| objective response rate | The objective response rate includes the complete remission and partial remission rate. | up to 9 weeks | 
| the score of functional assessment of cancer treatment-lung(FACT-L) | FACL-L is assessed at different time points.(Date of randomization,1 week after chemotherapy,every cycle of chemotherapy,every month of EGFR-TKI maintain treatment,up to 100 weeks) | up to 100weeks | 
| Number of participants with adverse events | The adverse events are assessed by National Cancer Institute-Common Toxicity Criteria(version3.0) (NCI-CTC). | Participants will be followed for the duration of treatment, an expected average of 52 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non small cell lung cancer, chemotherapy, epidermal growth factor receptor tyrosine kinase inhibitor, retreatment