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

Phase 2

Terminated

Conditions: Lung Cancer

Interventions: Drug: pemetrexed
Drug: enzastaurin
Drug: placebo
Drug: cisplatin

Registration Number: NCT00538681

Lead Sponsor: Eli Lilly and Company

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 35

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo + Pemetrexed + Cisplatin	placebo	-
Placebo + Pemetrexed + Cisplatin	pemetrexed	-
Enzastaurin + Pemetrexed + Cisplatin	pemetrexed	-
Enzastaurin + Pemetrexed + Cisplatin	enzastaurin	-
Enzastaurin + Pemetrexed + Cisplatin	cisplatin	-
Placebo + Pemetrexed + Cisplatin	cisplatin	-

Primary Outcome Measures

Name	Time	Method
Part 1: Evaluate Safety [Toxicity, Serious Adverse Events (SAEs) and Reasons for Participant's Discontinuation]	Cycle 1 (28-day cycle), Cycles 2, 3, 4, 5, and 6 (21-day cycles) and 30-day follow up	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.
Part 2: Compare Progression-Free Survival (PFS) Between the 2 Treatment Arms Through the Assessment of Tumor Response	Baseline to measured PD up to 5 months	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.

Secondary Outcome Measures

Name	Time	Method
Part 2: Number of Participants With a Complete Response (CR) or Partial Response (PR) (Response Rate)	Baseline to measured progressive disease (PD) up to 5 months	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.
Part 2: To Assess Biomarkers of the Disease State and Their Correlation to Clinical Outcome	Baseline, Cycle 1 (28-day cycle), Cycles 2, 3, 4, 5, and 6 (21-day cycles) and end of study up to 5 months	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.
Part 2: Overall Survival (OS)	Baseline to date of death from any cause up to 5 months	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.
Part 2: To Evaluate the Safety and Toxicity Profile of Study Treatments	Cycle 1 (28-day cycle), Cycles 2, 3, 4, 5, and 6 (21-day cycles) and 30-day follow-up	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.
Part 2: Duration of Disease Control (DDC) and Response	Baseline to measured PD up to 5 months	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.
Part 2: Time to Worsening of Symptoms (TWS)	Cycle 1 (28-day cycle), Cycles 2, 3, 4, 5, and 6 (21-day cycles) and 30-day follow-up	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.

Trial Locations

Locations (1): For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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Bucharest, Romania