A Study Comparing of Two Different Chemotherapy Regimens, in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This is a multicenter, open-label, randomized, two-arm Phase 2 study comparing pemetrexed plus best supportive care with best supportive care alone as maintenance therapy following first-line treatment with a pemetrexed-cisplatin combination in patients with advanced non-squamous non-small cell lung cancer. A total of approximately 100 patients are planned to be enrolled, and following completion of four cycles of pemetrexed-cisplatin (Induction Phase) those patients in which disease progression has not occurred will be randomized in a 2:1 ratio to one of two treatment arms (Maintenance Phase): Arm A (pemetrexed plus best supportive care) or Arm B (best supportive care alone).

Official Title
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A Randomized Phase 2 Study Comparing Pemetrexed Plus Best Supportive Care With Best Supportive Care as Maintenance, Following First-Line Treatment With Pemetrexed-Cisplatin, in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: pemetrexed
* Drug: Best Supportive Care


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: You must be at least 18 years old You must have been diagnosed with non-squamous non-small cell lung cancer (NSCLC) You must have had no prior systemic anticancer therapy for lung cancer You must live close enough to the study doctor to be able to visit regularly for follow up You must have signed informed consent form indicating your willingness to take part in this study Your laboratory and medical history and tests must meet study requirements Exclusion criteria: Treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry Prior radiotherapy and surgery should be completed at least 4 weeks prior to initiation of treatment Serious concomitant systemic disorder (e.g., active infection including human immunodeficiency virus, or unstable cardiovascular disease) Prior malignancy other than NSCLC, carcinoma in situ of the cervix, or nonmelanoma skin cancer unless treated at least 5 years previously with no subsequent evidence of recurrence Brain metastasis Presence of clinically significant (by physical exam) third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry Significant weight loss (greater than 10%), over the previous 6 weeks before study entry Concurrent administration of any other antitumor therapy Inability to interrupt aspirin or other non-steroidal anti-inflammatory agents for a 5-day period (8-day period for long-acting agents such as piroxicam) Inability or unwillingness to take folic acid, dexamethasone (or equivalent) or vitamin B12 supplementation Pregnancy or breast-feeding You are allergic to pemetrexed

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: A: Pemetrexed + Best Supportive Care<br>Pemetrexed: 500 milligrams per square meter (mg/m²) , intravenous (IV), Day 1 of each 21-day cycle for 6 cycles Best Supportive Care: Patients will receive best supportive care (dose, frequency, duration) as judged by their treating physician. | Drug: pemetrexed<br>* 500 mg/m², IV, Day 1 of each 21-day cycle for 6 cycles<br>* Other names: LY231514;Drug: Best Supportive Care<br>* Patients will receive best supportive care (dose, frequency, duration) as judged by their treating physician.<br>|
| Active Comparator: B: Best Supportive Care<br>Best Supportive Care: Patients will receive best supportive care (dose, frequency, duration) as judged by their treating physician. | Drug: Best Supportive Care<br>* Patients will receive best supportive care (dose, frequency, duration) as judged by their treating physician.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival During Maintenance Phase | Progression free survival is defined as the time from randomization until the date of progression of disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD is ≥20% increase in sum of longest diameter of target lesions. PD in maintenance phase uses the last lesion assessment prior to randomization as the baseline assessment. | Randomization to progression of disease (PD) or date of death from any cause up to 30.9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival During Overall Period (Induction Phase [IP] + Maintenance Phase [MP]) | Progression-free survival in overall period is defined as the time from the date of first dose of study drug during IP until the date of PD or death from any cause. PD was determined using RECIST criteria. PD is ≥20% increase in sum of longest diameter of target lesions. PD in overall period uses the screening lesion assessment prior to the induction phase as the baseline assessment. | First dose of study drug during IP to PD or date of death from any cause up to 33.6 months | 
| Overall Survival During Maintenance Phase | Overall survival in maintenance phase is defined as the time from randomization to death. Participants who were alive were censored at the last contact. | Randomization to PD or date of death from any cause up to 31.3 months | 
| Overall Survival During Overall Period (IP + MP) | Overall survival in overall period is defined as the time from first dose of study drug during IP to death. Participants who were alive were censored at the last contact. | First dose of study drug during IP to PD or date of death from any cause up to 34.1 months | 
| Number of Participants With Adverse Events (AEs) During Overall Period | The list of serious adverse events (SAEs) and other non-serious adverse events (AEs) are in Adverse Events Section. | First dose of study drug during IP through overall study completion (up to 34.3) months | 
| Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | Tumor response rate (%) is the number of responders (participants with best response of CR or PR) divided by the number of participants qualified for tumor response according to RECIST criteria multiplied by 100. Disease control rate is percentage of participants with a best response of stable disease [SD], PR, or CR. CR=disappearance of all target lesions; PR=30% decrease in sum of longest diameter of target lesions; PD is≥20% increase in sum of longest diameter of target lesions. SD= neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. | Randomization to measured PD up to 31.4 months |