First Line Chemotherapy Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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The purposes of this study are to determine: The safety of enzastaurin plus pemetrexed with carboplatin, pemetrexed with carboplatin, or docetaxel with carboplatin and any side effects that might be associated with the combination of these drugs. Whether the combination of enzastaurin plus pemetrexed and carboplatin or pemetrexed and carboplatin can help participants with non-small cell lung cancer (NSCLC) live longer, compared with the combination of docetaxel and carboplatin. Whether the combination of enzastaurin plus pemetrexed and carboplatin or pemetrexed and carboplatin can make your tumor smaller or disappear, and for how long, compared with the combination of docetaxel and carboplatin. The effects of enzastaurin plus pemetrexed with carboplatin, pemetrexed with carboplatin or docetaxel with carboplatin have on your disease related symptoms. The relation of smoking history and hormone replacement therapy (for women only) may have to your lung cancer treatment results. The effects of certain genes and proteins in samples of your blood and tumor tissue in order to learn more about NSCLC and how enzastaurin works in the body.

Official Title
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A Randomized, Open-label Phase II Study of Pemetrexed (Alimta) Plus Carboplatin With or Without Enzastaurin Hydrochloride, or Docetaxel Plus Carboplatin as First Line Treatment in Patients With Advanced Stage Non-small Cell Lung Cancer (NSCLC)

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: enzastaurin
* Drug: pemetrexed
* Drug: docetaxel
* Drug: carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: You must have been diagnosed with NSCLC. You must be able to visit the doctor's office weekly during the active treatment period and as needed during the study follow-up period. You must be willing and able to swallow capsules. Your entry labs and medical tests must meet study requirements. You must be willing to have blood samples drawn and tissue samples obtained for gene and protein testing. Exclusion Criteria: You have received radiation within 2 weeks of study enrollment. You have previously received any anti-cancer drug therapy for NSCLC. You have an active infection or other serious condition. You take aspirin or aspirin-like medication regularly and are not able to stop taking them for a few days during each cycle of chemotherapy. You have recently lost a significant amount of weight.

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: Enzastaurin/Pemetrexed/Carboplatin<br> | Drug: enzastaurin<br>* 1125-1200 milligrams (mg) loading dose then 500 mg, oral, daily, until disease progression<br>* Other names: LY317615;Drug: pemetrexed<br>* 500 milligrams per square meter (mg/m^2), intravenous (IV), once every (q) 21 days, six 21 day cycles or progressive disease<br>* Other names: Alimta;Drug: carboplatin<br>* Area under the curve (AUC) 6, IV, q 21 days, six 21 day cycles or progressive disease<br>|
| Experimental: Pemetrexed/Carboplatin<br> | Drug: pemetrexed<br>* 500 milligrams per square meter (mg/m^2), intravenous (IV), once every (q) 21 days, six 21 day cycles or progressive disease<br>* Other names: Alimta;Drug: carboplatin<br>* Area under the curve (AUC) 6, IV, q 21 days, six 21 day cycles or progressive disease<br>|
| Active Comparator: Docetaxel/Carboplatin<br> | Drug: docetaxel<br>* 75 mg/m^2, IV, q 21 days, six 21 day cycles or progressive disease<br>Drug: carboplatin<br>* Area under the curve (AUC) 6, IV, q 21 days, six 21 day cycles or progressive disease<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Disease Progression | Time to disease progression was defined as the time from randomization to the first date of documented disease progression or death if the participant dies due to disease progression. 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. For participants who have not had documented disease progression, time to disease progression was censored at the date of death or date of last visit. For participants who received other anti-tumor therapy prior to disease progression, time to disease progression was censored at the first available date of other anti-tumor therapy. | Baseline to measured PD up to 22.3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Biomarkers Associated With Clinical Outcomes | As specified in the protocol, tumor biomarker samples were collected from participants on the pemetrexed arms only but were not intended to be analyzed at the individual study level. | Baseline, Cycle 1, Cycle 2 (21-day cycle each), and 30-day post study treatment follow-up | 
| Assessment of Smoking History (All Participants) and Hormone Replacement Therapy (Female Participants Only) Associated With Clinical Outcomes | Data for smoking history and hormone replacement therapy were collected but were not intended to be analyzed at the individual study level. | Baseline | 
| Number of Participants With Adverse Events (AEs) or Deaths | Data presented are the number of participants who experienced 1 or more AEs or any serious AEs (SAEs) regardless of causality, or deaths during the study including 30 days after treatment discontinuation. A summary of SAEs and other non-serious AEs is located in the Reported Adverse Events section of this report. | Baseline through study completion up to 6 cycles (21-day cycle each) and 30-day safety follow-up | 
| Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale | The FACT-L version 4 scale is used to assess health-related quality of life (HRQoL) in participants with lung cancer. The FACT-L has 5 subscales: Physical Well-Being (PWB), Social and Family Well-Being (SFWB) and Functional Well-Being (FWB) subscales which include 7 items each, Emotional Well-Being (EWB) subscale which includes 6 items, and a Lung-Cancer Specific (LCS) subscale which include 7 items. Total FACT-L is the sum of all 5 subscales. Each item is scored from 0 to 4 giving a total overall score from 0 equal to worst quality of life to 136 equal to best quality of life. The Least Square (LS) mean was calculated using an analysis of covariance (ANCOVA) model adjusted for change scores and baseline scores. | Baseline, Cycle 1 (Week 3), Cycle 2 (Week 6), Cycle 3 (Week 9), Cycle 4 (Week 12), Cycle 5 (Week 15) and Cycle 6 (Week 18) [21-day cycle each] | 
| Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale | The FACT-Taxane version 4 scale is used to assess HRQoL in participants receiving taxane chemotherapy. The FACT-taxane has 5 subscales: PWB, SFWB, and FWB subscales which include 7 items each, EWB subscale which includes 6 items, and a taxane subscale which include 16 items and has two domains (neurotoxicity and taxane). Total FACT-Taxane is the sum of all the 5 subscales. Each item is scored from 0 to 4 giving a total overall score from 0 worst quality of life to 172 best quality of life. The LS mean was calculated using an ANCOVA model adjusted for change scores and baseline scores. | Baseline, Cycle 1 (Week 3), Cycle 2 (Week 6), Cycle 3 (Week 9), Cycle 4 (Week 12), Cycle 5 (Week 15) and Cycle 6 (Week 18) [21-day cycle each] | 
| Overall Survival (OS) | OS was the duration from the date of randomization to the date of death from any cause. For participants who were alive, OS was censored at the date of last follow-up visit or at the date of last contact. | Baseline to date of death from any cause up to 35 months | 
| Number of Participants With Complete Response (CR) or Partial Response (PR) [Tumor Response] | Response was defined using RECIST, version 1.0 criteria. Participants with a best response of CR or 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. | Baseline to measured PD up to 22.3 months | 
| Duration of CR or PR (Duration of Response) | The duration of a CR or PR was defined as the time from first objective status assessment of CR or PR to the first time of progression or death due to any cause. Response was defined using RECIST, version 1.0 criteria. 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. | Date of first response to the date of progression or death due to any cause up to 22.3 months | 
| Time-to-Treatment Failure (TTF) | TTF was defined as the time from randomization to the first observation of PD, death due to any cause, or early discontinuation of treatment. Response was defined using RECIST, version 1.0 criteria. PD was defined as having at least a 20% increase in sum of longest diameter of target lesions. TTF was censored at the date of the last follow-up visit for participants who did not discontinue early, who were still alive, and who have not progressed. | Baseline to stopping treatment up to 14.1 months |