Study of Enzastaurin Versus Placebo With Pemetrexed for Participants With Advanced or Metastatic Lung Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine if the combination of enzastaurin and pemetrexed can extend survival time without progression of disease for participants who have advanced or metastatic non-small cell lung cancer (NSCLC).

Official Title
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A Phase 2 Double-Blind Randomized Study of Oral Enzastaurin HCl Versus Placebo Concurrently With Pemetrexed (Alimta®) as Second-Line Therapy in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: enzastaurin
* Drug: placebo
* Drug: pemetrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Laboratory confirmed diagnosis of NSCLC with locally advanced or metastatic disease which cannot be cured. Participants must have disease which progressed after 1 prior systemic cytotoxic chemotherapy regimen for advanced disease. At least 1 measurable lesion. Must have stopped all previous systemic therapies for cancer for at least 2 weeks prior to enrollment. Must be able to follow study guidelines and be able to show up for appointments. 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. Previous treatment with enzastaurin or pemetrexed. Concurrent administration of any other antitumor therapy. Inability to swallow tablets. Pregnant or breastfeeding.

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: Pemetrexed + Enzastaurin<br> | Drug: enzastaurin<br>* 1125 milligrams (mg) loading dose then 500 mg, oral, daily Cycle 1 (28 days), subsequent cycles 21 days, until disease progression<br>* Other names: LY317615;Drug: pemetrexed<br>* 500 milligrams per square meter (mg/m^2), intravenous (IV), day 8 Cycle 1 (28 days), day 1 subsequent cycles (21 days), until disease progression<br>* Other names: Alimta;|
| Placebo Comparator: Pemetrexed + Placebo<br> | Drug: placebo<br>* oral, daily<br>Drug: pemetrexed<br>* 500 milligrams per square meter (mg/m^2), intravenous (IV), day 8 Cycle 1 (28 days), day 1 subsequent cycles (21 days), until disease progression<br>* Other names: Alimta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS was defined as the time from date of randomization to the first documented observation of disease progression or death from any cause. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive disease (PD) was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. PFS was censored at the date of the last objective progression-free disease assessment for participants who did not experience PD or death at the data inclusion cut-off date. | Baseline to measured progressive disease up to 9.92 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was defined as the duration from the date of randomization to the date of death from any cause. For participants who were alive at the time of the data inclusion cutoff, OS was censored at the date the participant was last known to be alive. | Baseline to date of death from any cause up to 12.32 months | 
| Time-to-Worsening (TW) in Lung Cancer Symptom Scale (LCSS) - Health Related Quality of Life (HRQoL) Subscale | LCSS is a participant rated lung cancer instrument which consisted of 6 disease related symptoms (appetite, cough, fatigue, dyspnea, hemoptysis, and pain) and 3 quality of life (QoL) items (activity status, symptomatic distress, and overall QoL). TW in LCSS-HRQoL was measured from the date of enrollment to the first date of a 15 millimeters (mm) worsening in the 9th LCSS item on QoL. LCSS-HRQoL was measured on the 100-mm visual analogue scale (VAS) with the scores ranging from 0 (best response and very high HRQoL) to 100-mm (worse response and very low HRQoL). TW-HRQoL was censored at the date of the participant's last LCSS assessment for participant without a 15-mm increase on the 100-mm VAS. | Baseline to disease worsening up to 10.58 months | 
| Duration of Disease Control (DDC) | DDC was defined as the time from randomization to the first documented observation of disease progression or death from any cause and was limited to the participants with a best tumor response of complete response (CR), partial response (PR), or stable disease (SD). Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive disease (PD) was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. SD was defined as small changes that did not meet the above criteria. DDC was censored at the date of the last objective progression-free disease assessment for participants who did not experience PD or death. | Baseline to measured progressive disease up to 9.92 months | 
| Percentage of Participants With Complete Response or Partial Response (Tumor Response Rate) | Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Participants with a best response of complete response (CR) or partial response (PR) were considered to have had a tumor response. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Percentage of participants was calculated as the total number of participants affected divided by the number of participants analyzed then multiplied by 100. | Baseline to measured progressive disease up to 9.92 months | 
| Tumor Biomarkers | Protein expression was measured using an Immunohistochemistry (IHC) assay from the tumor tissue samples. IHC histo-scores (H-scores) were determined separately for each of the 3 biomarkers: folate receptor alpha (FR alpha) in cytoplasm and apical membrane, thymidylate synthase (TS) in cytoplasm and nucleus, and thyroid transcription factor-1 (TTF1) in the nucleus. Tumor tissue samples were to be scored using a 0 (negative, no staining) to 3+ (brightest staining) scoring system for cytoplasmic and nuclear staining. IHC H-score was calculated using the formula: 1 * (percentage of cells stained 1+) + 2 * (percentage of cells stained 2+) + 3 * (percentage of cells stained 3+), giving a minimum score of 0 to a maximum score of 300. The maximum score indicates the strongest expression. | Tumor samples collected at baseline |