Study for Participants With Advanced, Not Amenable to Surgery, or Metastatic Lung Cancer Comparing Treatment With Pemetrexed + Cisplatin + Enzastaurin Versus Pemetrexed + Cisplatin + Placebo

Study Overview
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Brief Summary
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This study is intended for participants with advanced, not amenable to surgery, or metastatic lung cancer who have not received any prior chemotherapy. The study will be conducted in 2 parts: Part 1 is intended to evaluate safety of pemetrexed + cisplatin + enzastaurin combination chemotherapy Part 2 whose main objective is to compare the efficacy of pemetrexed + cisplatin + enzastaurin versus pemetrexed + cisplatin + placebo. Participants to be included in Part 2 are those with Nonsquamous Non-Small Cell Lung Cancer (NSCLC).

Official Title
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Randomized, Double-Blind, Placebo Controlled, Phase 2 Study of Pemetrexed and Cisplatin Plus Enzastaurin Versus Pemetrexed and Cisplatin Plus Placebo in Chemonaive Patients With Advanced, Unresectable, or Metastatic (Stage IIIB or IV) Nonsquamous Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of advanced NSCLC not amenable to curative treatment. Participants enrolling in Part 2 of the study must have the above stated diagnosis of NSCLC that is also of nonsquamous histology. no prior systemic therapies [chemotherapy, et cetera (etc.)] or pleurodesis with chemotherapy for this disease prior radiotherapy is allowed but must be completed at least 2 weeks before study enrollment and participant must be recovered from the acute toxic effects have a good performance status participant must sign an informed consent document Exclusion Criteria: participant had myocardial infarction occurring less than 6 months before inclusion, uncontrolled arrhythmia, symptomatic angina pectoris, or cardiac failure not controlled by medications participant is unable to swallow tablets participant is taking a certain medicine to control seizure activity, called enzyme inducing antiepileptic drugs and is not able to stop taking the medicine prior to enrolling in the study participant is unable to interrupt aspirin and/or other anti-inflammatory agents participant is unwilling or unable to take vitamin supplementation (folic acid and vitamin B12) or medications to prevent side effects

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enzastaurin + Pemetrexed + Cisplatin<br> | Drug: enzastaurin<br>* 1125 milligrams (mg) loading dose then 500 mg, oral (po), daily (QD), until disease progression<br>* Other names: LY317615;Drug: pemetrexed<br>* 500 milligrams/square meter (mg/m²), intravenously (IV), every 21 days, for each 21-day cycle<br>* Other names: Alimta;Drug: cisplatin<br>* 75 mg/m², IV, every 21 days, for each 21-day cycle<br>|
| Placebo Comparator: Placebo + Pemetrexed + Cisplatin<br> | Drug: pemetrexed<br>* 500 milligrams/square meter (mg/m²), intravenously (IV), every 21 days, for each 21-day cycle<br>* Other names: Alimta;Drug: cisplatin<br>* 75 mg/m², IV, every 21 days, for each 21-day cycle<br>Drug: placebo<br>* po, QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Evaluate Safety [Toxicity, Serious Adverse Events (SAEs) and Reasons for Participant's Discontinuation] | Presented are data that evaluates safety based on toxicity using Common Terminology Criteria for Adverse Events (CTCAE v3.0), SAEs, and discontinuations due to SAEs or other non-serious adverse events (AE's) of study participants. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Event module. | Cycle 1 (28-day cycle), Cycles 2, 3, 4, 5, and 6 (21-day cycles) and 30-day follow up | 
| Part 2: Compare Progression-Free Survival (PFS) Between the 2 Treatment Arms Through the Assessment of Tumor Response | PFS was defined as the time from date of first dose to the first observation of disease progression or death due to any cause. For participants not known to have died as of the data cut-off date and who did not have objective progressive disease (PD), PFS was censored at the date of the last objective progression-free assessment. For participants who received subsequent anticancer therapy (after discontinuation from the study treatment) prior to objective disease progression or death, PFS was censored at the date of last objective progression-free assessment prior to the initiation of post discontinuation anticancer therapy. PFS was calculated and analyzed based on an alternative definition of censoring; for each participant who is not known to have died or who have had objective disease progression as of the data cut-off date, PFS was censored at the date of last prior contact. Zero participants were analyzed in this outcome as study was terminated early. | Baseline to measured PD up to 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 2: To Evaluate the Safety and Toxicity Profile of Study Treatments | The safety and toxicity profile for Part 2 was defined as serious adverse events (SAEs) and other non-serious adverse events (AEs). A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Event module. | Cycle 1 (28-day cycle), Cycles 2, 3, 4, 5, and 6 (21-day cycles) and 30-day follow-up | 
| Part 2: Number of Participants With a Complete Response (CR) or Partial Response (PR) (Response Rate) | Response rate was defined using Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria. Complete Response (CR) was defined as the disappearance of all target lesions. Partial Response (PR) was defined as having at least a 30% decrease in sum of longest diameter (LD) of target lesions. Best response was confirmed by a second assessment in ≥28 days. Response rate was defined as the number of participants with best response of CR or PR divided by the total number of treated participants. Zero participants were analyzed in this outcome as study was terminated early. | Baseline to measured progressive disease (PD) up to 5 months | 
| Part 2: Overall Survival (OS) | OS time was defined as the time from the date of study enrollment to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS was censored at the last contact date (last contact for participants in post discontinuation was equal to the last known alive date in mortality status). Zero participants were analyzed in this outcome as study was terminated early. | Baseline to date of death from any cause up to 5 months | 
| Part 2: Duration of Disease Control (DDC) and Response | DDC and response defined as time from complete response (CR), partial response (PR) or stable disease (SD) to first date of objectively determined progressive disease (PD) or death from any cause using RECIST (v1.0) criteria. CR defined as disappearance of all target lesions. PR defined as having ≥30% decrease in sum of longest diameter (LD) of target lesions. PD defined as having ≥20% increase in the sum of the LD of target lesions. SD defined as small changes not meeting above criteria. Participants not known to have died as of data cut-off date, had no objective PD or were lost to follow-up, DCC was censored at date of last objective progression-free assessment (OPFA). Participants who received subsequent anticancer therapy (after discontinuation from study treatment) prior to objective PD or death were censored at date of last OPFA prior to initiation of post discontinuation anticancer therapy. Zero participants were analyzed in this outcome as study was terminated early. | Baseline to measured PD up to 5 months | 
| Part 2: Time to Worsening of Symptoms (TWS) | TWS was measured from the date of study enrollment to the first date of a worsening in any of the 6 Lung Cancer Symptom Scale (LCSS) symptoms (appetite, cough, fatigue, shortness of breath, hemoptysis and pain). Participants marked each symptom on a visual analog scale (VAS) that ranged from 0 millimeter (mm) (as good as it can be/none) to 100 mm (as bad/much as it could be). TWS was also measured individually for each of the 6 symptoms independently and were also measured from the date of enrollment to the first date of worsening in pain. For both measurements, worsening was defined as a 15-mm increase from baseline in the participant-reported score for any symptom. Participants who are not known to have had a worsening TWS were censored at the date of the participant's last LCSS assessment. Zero participants were analyzed in this outcome as study was terminated early. | Cycle 1 (28-day cycle), Cycles 2, 3, 4, 5, and 6 (21-day cycles) and 30-day follow-up | 
| Part 2: To Assess Biomarkers of the Disease State and Their Correlation to Clinical Outcome | Presented are data that evaluates of biomarkers relevant to the study drug and the disease state of the participant's clinical outcome. Zero participants were analyzed in this outcome as study was terminated early. | Baseline, Cycle 1 (28-day cycle), Cycles 2, 3, 4, 5, and 6 (21-day cycles) and end of study up to 5 months |