Assess the Efficacy, Safety and Tolerability of Gefitinib (Iressa® 250mg) as Maintenance Therapy in Locally Advanced or Metastatic (Stage IIIB/IV) Non Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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This is a double blind, multicentre, randomized, placebo-controlled study. The eligible patients will be randomized to receive gefitinib or placebo at 1:1 ratio. This study will recruit 296 male or female, histologically or cytologically diagnosed locally advanced or metastatic NSCLC patients with a World Health Organization (WHO) Performance Status (PS) 0-2. Patients must have completed 4 cycles of platinum based first line doublet chemotherapy without experiencing disease progression or unacceptable toxicity. The chemotherapy shall be given every 3 weeks, which includes cisplatin or carboplatin, combined with any one of the following: gemcitabine, paclitaxel, docetaxel, vinorelbine.

Official Title
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A Placebo-Controlled, Multicentre, Randomised, Parallel Group, Trial to Assess the Efficacy, Safety and Tolerability of Gefitinib (Iressa® 250mg) as Maintenance Therapy in Locally Advanced or Metastatic (StageIIIB/IV) Non Small Cell Lung Cancer (NSCLC) Chinese Patients Who HaveNot Experienced Disease Progression or Unacceptable Toxicity During Front Line Standard Platinum-Based Chemotherapy

Conditions
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Non-small Cell Lung Cancer (NSCLC)

Intervention / Treatment
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* Drug: Gefitinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed locally advanced or metastatic (stage=IIIB/IV) non-small cell lung cancer (NSCLC) before the front line chemotherapy. Note: sputum cytology alone is not acceptable Patients have completed 4 cycles of first line platinum contained doublet chemotherapy without progression or intolerable toxicity. Patients with PR or SD on study entry need to have one or more measurable lesions according to RECIST criteria. The study treatment should be started at least 3 weeks (21 days) but no more than 6 weeks (42 days) since last dose of chemotherapy, and within 4 weeks (28 days) since last tumour assessment. Exclusion Criteria: Prior exposure to monoclonal antibodies or small molecule inhibitors against EGFR receptors. (e.g. gefitinib, erlotinib, C225) Patients with previously diagnosed and treated CNS metastases or spinal cord compression may be considered if they are clinically stable and have been discontinued from steroid therapy for at least 4 weeks prior to first dose of study medication. Any evidence of clinically active interstitial lung disease (patients with chronic, stable, radiographic changes who are asymptomatic need not be excluded) Known biomarker status of one or more of the following: Tumour EGFR gene copy number, tumour EGFR gene mutation status, tumour EGFR protein expression.

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: gefitinib<br>Gefitinib (Iressa® 250 mg) 1 tablet daily | Drug: Gefitinib<br>* Dose form: 250 mg/tablet; Route: oral; Frequency: 1 tablet per day; Duration: until to objective PD<br>* Other names: Iressa;|
| Placebo Comparator: placebo<br>placebo 1 tablet daily | Drug: Placebo<br>* To match Gefitinib<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS will be calculated from the tumour measurements collected at each tumour assessment per the RECIST criteria and/or the date of patient death. Progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first.The primary analysis of PFS will be performed when at least 265 events have occurred, which is expected to occur approximately. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | The OS will be assessed from the time of randomisation to death from any cause. For patients not known to have died(which may include those who have been lost to follow up or who have withdrawn from the study for whatever reason), OS will be censored for the analysis at the last date at which the patients were known to be alive. | The OS will be assessed from the time of randomization to death from any cause.For patients not known to have died or who have withdrawn from the study for whatever reason,OS will be censored at the last date at which patients were known to be alive. | 
| Objective Tumour Response (ORR) | The objective tumour response will be calculated as the number of patients with CR or PR per RECIST Criteria. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | TTumour assessment using RECIST will be performed at baseline then every 42 days (6 weeks) ± 7 days (1 week) from randomisation until objective progression or death from any cause. | 
| Disease Control Rate (DCR) | DCR will be calculated as the number of patients with CR, PR or sustained SD≥6 weeks per RECIST Criteria. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase | Tumour assessment using RECIST will be performed at baseline then every 42 days (6 weeks) ± 7 days (1 week) from randomisation until objective progression or death from any cause. | 
| Symptom Improvement | Symptom improvement will be assessed from the 7-question Lung Cancer Subscale domain score derived from the FACT-L questionnaire. It is defined as an increase of two or more points on the LCS from randomization, maintained for 21 or more days. It will be calculated as the number of patients analysed with improvement. | at randomization, every 6 weeks until disease progression, and at discontinuation. | 
| Adverse Event | Appropriate description of AEs and laboratory data/vital signs will be produced. Number of patients who had at least one adverse events will be calculated. | AEs and SAEs must be collected from the time that the main study informed consent is obtained to 28 days after discontinuation of study drug. Any ongoing AE or SAE at discontinuation of study treatment and during 28 day follow-up period must be monitored | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-small cell lung cancer (NSCLC), Gefitinib