Pemetrexed and Best Supportive Care Versus Placebo and Best Supportive Care in Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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This study is a randomized Phase 3, double-blind study of maintenance pemetrexed plus best supportive care versus placebo plus best supportive care in NSCLC. Participants must have received 1 of 6 induction regimens for 4 cycles and did not have progressive disease prior to randomization (enrollment) into this trial.

Official Title
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A Phase 3, Double-Blind, Placebo-Controlled Study of Maintenance Pemetrexed Plus Best Supportive Care Versus Best Supportive Care Immediately Following Induction Treatment for 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: Placebo
* Other: Best Supportive Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic or cytologic diagnosis of NSCLC Stage IIIB (with pleural effusion and/or positive supraclavicular lymph nodes) or Stage IV prior to induction therapy. Participants must have had 1 of the following induction therapies for treatment for Stage IIIB (with pleural effusion and/or positive supraclavicular lymph nodes) or IV NSCLC: Gemcitabine plus carboplatin, paclitaxel plus carboplatin, or docetaxel plus carboplatin, gemcitabine plus cisplatin, paclitaxel plus cisplatin or docetaxel plus cisplatin. Participants must have received only 1 chemotherapeutic doublet lasting precisely 4 cycles. Induction regimens must be based on 21-day cycles. Documented evidence of a tumor response of complete response (CR), partial response (PR), or stable disease (SD). Tumor assessment must occur between Cycle 4 (Day 1) of induction therapy and the date of randomization. This response does not have to be confirmed in order for the participant to be randomized. Positron emission tomography (PET) scans and ultrasounds may not be used for lesion measurements for response determination. Exclusion Criteria: With the exception of those chemotherapies listed as inclusion criterion, participants will not be included if they have received prior systemic anticancer therapy (including adjuvant early-stage treatment for NSCLC) or any systemic treatment for any other cancer. Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. Inability to comply with protocol or study procedures. A serious concomitant systemic disorder that would compromise the participant's ability to complete the study. A serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pemetrexed and Best Supportive Care<br> | Drug: Pemetrexed<br>* 500 milligrams per square meter (mg/m^2), intravenous (IV) administration, every (q) 21 days, until disease progression<br>* Other names: Alimta;Other: Best Supportive Care<br>* Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.<br>|
| Placebo Comparator: Placebo and Best Supportive Care<br> | Drug: Placebo<br>* IV administration, q 21 days<br>Other: Best Supportive Care<br>* Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) Time | PFS time was the elapsed time from the date of randomization to the first date of objective progression of disease or death from any cause. PFS was censored at the date of the participant's last tumor assessment for participants who were not known to have died or to have PD as of the data-inclusion cut-off date for analysis. PD, defined using Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0), was at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. | Randomization to measured PD or death from any cause (up to 41 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) Time | OS time was the elapsed time from the date of randomization to the date of death from any cause. OS was censored at the last date of contact for participants who were not known to have died as of the data-inclusion cut-off date for analysis. | Randomization to date of death from any cause (up to 41 months) | 
| Time to Objective Progressive Disease (TPD) | TPD was the elapsed time from the date of randomization to the first date of objective PD. TPD was censored at the date of the participant's last tumor assessment for participants who were not known to have PD as of the data-inclusion cut-off date for analysis or who died without objective PD. PD, defined using RECIST v1.0, was at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. | Randomization to measured PD (up to 41 months) | 
| Time to Worsening of Symptoms (TWS) | TWS was the elapsed time from the date of randomization to the first date of worsening [defined as a 15-millimeter (mm) increase from baseline based on a 100-mm scale] of each symptom and summary item in the Lung Cancer Symptom Scale (LCSS). The participant-reported LCSS was a 9-item questionnaire. Six items were symptom-specific measures for lung cancer (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain), and 3 summation items described total symptomatic distress, interference with activity level, and global quality of life. Participant (pt) responses to each item were measured using visual analogue scales (VAS) from 0 (for best outcome) to 100 (for worst outcome). TWS was censored at the date of the last LCSS assessment for pts who were not known to have LCSS worsening. | Randomization to worsening of each LCSS item (up to 39 months) | 
| Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Tumor Response Rate) | Response was defined using RECIST v1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined either A) at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LDs or B) complete disappearance of target lesions, with persistence (but not worsening) of 1 or more nontarget lesions. In either case, no new lesions may have appeared. The percentage of participants with CR or PR=(Number of participants with CR or PR)/(Number of participants assessed)*100. | Baseline to measured PD (up to 41 months) | 
| Number of Participants With Adverse Events (AEs) | Clinically significant events were defined as serious adverse events (SAEs) and other non-serious AEs regardless of causality. A summary of serious and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. | Baseline to study completion (up to 41 Months) | 
| Maximum Improvement Over Baseline in Individual Symptom Scores and Quality of Life Using the LCSS | The participant-reported LCSS was a 9-item questionnaire. Six items were symptom-specific measures for lung cancer (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain), and 3 summation items described total symptomatic distress, interference with activity level, and global quality of life. Participant responses to each item were measured using VAS from 0 (for best outcome) to 100 (for worst outcome). The average symptom burden index (ASBI) was the mean of the 6 symptom-specific items. The LCSS total score was the mean of the 9 items. | Baseline through 30 days post discontinuation of study treatment (up to 39 Months) |