Chemotherapy for Patients With Non-Small Cell Lung Cancer Who Are Non-Smokers

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy and safety of chemotherapy followed sequentially by gefitinib versus chemotherapy alone in the first line treatment of non-small cell lung cancer (NSCLC). This study will be conducted in Asian patients who are classified as 'never smoker' since it is suggested that these patients are more likely to respond favorably to treatment with gefitinib.

Official Title
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A Phase 2 Trial of Pemetrexed and Cisplatin Followed Sequentially by Gefitinib Versus Pemetrexed and Cisplatin in Asian Never Smoker Patients With Advanced Non-Small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Pemetrexed
* Drug: Cisplatin
* Drug: Gefitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic or cytologic diagnosis non-small cell lung cancer (NSCLC) (Stage IIIB or IV) Have not received any prior chemotherapy, molecular therapy, immunotherapy, biological therapy, or radiotherapy. Exception: palliative radiotherapy that is completed at least 4 weeks prior to study enrolment. Have 'never smoked' (defined as having smoked <100 cigarettes during his/her lifetime) Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 Exclusion Criteria: Concurrent administration of any other tumor therapy Other co-existing malignancies Pregnancy or breast feeding Serious concomitant disorders Inability or unwillingness to take folic acid or vitamin B12 supplementation

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pemetrexed/Cisplatin/Gefitinib<br>Pemetrexed 500 milligrams per meters squared (mg/m2) plus cisplatin 75 mg/m2 administered by intravenous (IV) infusion once every 3 weeks for 4 cycles without progression followed by gefitinib 250 mg administered orally, once daily, until disease progression or unacceptable toxicity. | Drug: Pemetrexed<br>* 500 milligrams per meter squared (mg/m2), administered by intravenous (IV) infusion every 21 days for 4 cycles (1-4) or 500 mg/m2, IV, every 21 days until disease progression or unacceptable toxicity.<br>* Other names: Alimta;Drug: Cisplatin<br>* 75 mg/m2, IV, every 21 days for 4 cycles (1-4) or 75 mg/m2, IV, every 21 days for 4 cycles with optional continuation for 2 additional cycles until disease progression or unacceptable toxicity<br>Drug: Gefitinib<br>* 250 mg, administered orally once daily beginning at Cycle 5 until disease progression or unacceptable toxicity<br>|
| Experimental: Pemetrexed/Cisplatin<br>Pemetrexed 500 milligrams per meters squared (mg/m2) plus cisplatin 75 mg/m2 administered by intravenous (IV) infusion once every 3 weeks for 4 cycles without progression followed by pemetrexed 500 mg/m2 administered by IV infusion (with optional cisplatin 75 mg/m2 for up to 2 additional cycles) until disease progression or unacceptable toxicity. | Drug: Pemetrexed<br>* 500 milligrams per meter squared (mg/m2), administered by intravenous (IV) infusion every 21 days for 4 cycles (1-4) or 500 mg/m2, IV, every 21 days until disease progression or unacceptable toxicity.<br>* Other names: Alimta;Drug: Cisplatin<br>* 75 mg/m2, IV, every 21 days for 4 cycles (1-4) or 75 mg/m2, IV, every 21 days for 4 cycles with optional continuation for 2 additional cycles until disease progression or unacceptable toxicity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | Defined as the time from randomization to the first observation of disease progression, or death due to any cause. | Baseline to first observation of disease progression or death, 12 weeks up to 31 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Tumor Response | Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes not meeting above criteria. Responder is a participant exhibiting a best overall study response of CR or PR. | Baseline to measured response or death, 12 weeks up to 31 months | 
| Duration of Response for Responders | The duration of a complete response (CR; the disappearance of all target lesions) or partial response (PR; at least a 30% decrease in the sum of the longest diameter of target lesions) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause. A responder is a patient exhibiting a best overall study response of CR or PR. | Time of response to progressive disease or death, 12 weeks up to 31 months | 
| Overall Survival | Overall survival is the duration from enrollment to death. For patients who are alive, overall survival is censored at the last contact. Median overall survival could not be estimated as most participants were living at the end of the study. 25 participants from each treatment group were censored. In place of this outcome measure, the percentage of participants who died during the study are provided in the Post-Hoc Analysis Outcome Measure: Percentage of Participants Who Died During the Study. | Baseline to date of death from any cause, 12 weeks up to 31 months |