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

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00308750
• Collaborator: (none)
• Enrollment: 218
• Locations: 4
• Arms: 3
• Duration (Months): 40
• Patients Per Site: 54.5
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Drug: enzastaurin; Drug: pemetrexed; Drug: docetaxel; Drug: carboplatin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 218 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Enzastaurin/Pemetrexed/Carboplatin	Drug: enzastaurin; 1125-1200 milligrams (mg) loading dose then 500 mg, oral, daily, until disease progression; Other Names: LY317615 ; Drug: pemetrexed; 500 milligrams per square meter (mg/m^2), intravenous (IV), once every (q) 21 days, six 21 day cycles or progressive disease; Other Names: LY231514 Alimta ; Drug: carboplatin; Area under the curve (AUC) 6, IV, q 21 days, six 21 day cycles or progressive disease
Experimental: Pemetrexed/Carboplatin	Drug: pemetrexed; 500 milligrams per square meter (mg/m^2), intravenous (IV), once every (q) 21 days, six 21 day cycles or progressive disease; Other Names: LY231514 Alimta ; Drug: carboplatin; Area under the curve (AUC) 6, IV, q 21 days, six 21 day cycles or progressive disease
Active Comparator: Docetaxel/Carboplatin	Drug: docetaxel; 75 mg/m^2, IV, q 21 days, six 21 day cycles or progressive disease; Drug: carboplatin; Area under the curve (AUC) 6, IV, q 21 days, six 21 day cycles or progressive disease

Outcome Measures

Primary Outcome Measures

1. Time to Disease Progression [Baseline to measured PD up to 22.3 months]

   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.

Secondary Outcome Measures

1. Tumor Biomarkers Associated With Clinical Outcomes [Baseline, Cycle 1, Cycle 2 (21-day cycle each), and 30-day post study treatment follow-up]

   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.

2. Assessment of Smoking History (All Participants) and Hormone Replacement Therapy (Female Participants Only) Associated With Clinical Outcomes [Baseline]

   Data for smoking history and hormone replacement therapy were collected but were not intended to be analyzed at the individual study level.

3. Number of Participants With Adverse Events (AEs) or Deaths [Baseline through study completion up to 6 cycles (21-day cycle each) and 30-day safety follow-up]

   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.

4. Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale [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]]

   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.

5. Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale [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]]

   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.

6. Overall Survival (OS) [Baseline to date of death from any cause up to 35 months]

   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.

7. Number of Participants With Complete Response (CR) or Partial Response (PR) [Tumor Response] [Baseline to measured PD up to 22.3 months]

   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.

8. Duration of CR or PR (Duration of Response) [Date of first response to the date of progression or death due to any cause up to 22.3 months]

   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.

9. Time-to-Treatment Failure (TTF) [Baseline to stopping treatment up to 14.1 months]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
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.	Burlington	North Carolina	United States	27215
2	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.	Chapel Hill	North Carolina	United States	27599
3	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.	Columbia	South Carolina	United States	29210
4	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.	Houston	Texas	United States	77060

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00308750
• Other Study ID Numbers: 10651; H6Q-US-S004
• First Posted: Mar 30, 2006
• Last Update Posted: May 13, 2021
• Last Verified: Apr 1, 2021

• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carboplatin; Docetaxel; Pemetrexed

Study Results

Participant Flow

Pre-assignment Detail	Presented in the participant flow are the reasons participants discontinued from study treatment.

Arm/Group Title	Enzastaurin/Pemetrexed/Carboplatin	Pemetrexed/Carboplatin	Docetaxel/Carboplatin
Arm/Group Description	Enzastaurin loading dose of 1125 milligrams (mg) or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 milligrams per square meter (mg/m^2) and carboplatin [area under the curve (AUC)] 6 milligrams*minutes per milliliter (mg*min/mL) as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel 75 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Period Title: Overall Study
STARTED	72	74	72
Received at Least 1 Dose of Study Drug	67	72	70
COMPLETED	0	34	23
NOT COMPLETED	72	40	49

Baseline Characteristics

Arm/Group Title	Enzastaurin/Pemetrexed/Carboplatin	Pemetrexed/Carboplatin	Docetaxel/Carboplatin	Total
Arm/Group Description	Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel 75 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Total of all reporting groups
Overall Participants	72	74	72	218
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.2 (9.8)	64.0 (10.0)	64.0 (9.1)	64.4 (9.8)
Sex: Female, Male (Count of Participants)
Female	31 43.1%	33 44.6%	30 41.7%	94 43.1%
Male	41 56.9%	41 55.4%	42 58.3%	124 56.9%
Race/Ethnicity, Customized (Count of Participants)
African	5 6.9%	11 14.9%	8 11.1%	24 11%
Caucasian	62 86.1%	63 85.1%	63 87.5%	188 86.2%
Hispanic	5 6.9%	0 0%	1 1.4%	6 2.8%
Region of Enrollment (Count of Participants)
United States	72 100%	74 100%	72 100%	218 100%
Disease Stage at Study Entry (Count of Participants)
Stage IIIB	6 8.3%	5 6.8%	6 8.3%	17 7.8%
Stage IV	66 91.7%	69 93.2%	66 91.7%	201 92.2%

Outcome Measures

1. Primary Outcome

Title	Time to Disease Progression
Description	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.
Time Frame	Baseline to measured PD up to 22.3 months

Outcome Measure Data

Analysis Population Description

All randomized participants. Twenty (20) participants in Enzastaurin/Pemetrexed/Carboplatin group, 15 participants in Pemetrexed/Carboplatin group, and 17 participants in Docetaxel/Carboplatin group were censored for analysis.

Arm/Group Title	Enzastaurin/Pemetrexed/Carboplatin	Pemetrexed/Carboplatin	Docetaxel/Carboplatin
Arm/Group Description	Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel 75 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Measure Participants	52	59	55
Median (95% Confidence Interval) [months]	4.6	6.0	4.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzastaurin/Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.40
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.19
	Comments
	Method	Log Rank
	Comments

2. Secondary Outcome

Title	Tumor Biomarkers Associated With Clinical Outcomes
Description	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.
Time Frame	Baseline, Cycle 1, Cycle 2 (21-day cycle each), and 30-day post study treatment follow-up

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed due to insufficient samples being collected.

Arm/Group Title	Enzastaurin/Pemetrexed/Carboplatin	Pemetrexed/Carboplatin	Docetaxel/Carboplatin
Arm/Group Description	Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel 75 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Measure Participants	0	0	0

3. Secondary Outcome

Title	Assessment of Smoking History (All Participants) and Hormone Replacement Therapy (Female Participants Only) Associated With Clinical Outcomes
Description	Data for smoking history and hormone replacement therapy were collected but were not intended to be analyzed at the individual study level.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed due to insufficient samples being collected.

Arm/Group Title	Enzastaurin/Pemetrexed/Carboplatin	Pemetrexed/Carboplatin	Docetaxel/Carboplatin
Arm/Group Description	Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel 75 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Measure Participants	0	0	0

4. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) or Deaths
Description	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.
Time Frame	Baseline through study completion up to 6 cycles (21-day cycle each) and 30-day safety follow-up

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Enzastaurin/Pemetrexed/Carboplatin	Pemetrexed/Carboplatin	Docetaxel/Carboplatin
Arm/Group Description	Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel 75 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Measure Participants	67	72	70
AEs	63 87.5%	70 94.6%	69 95.8%
SAEs	35 48.6%	20 27%	26 36.1%
Deaths Due to AEs	3 4.2%	5 6.8%	4 5.6%

5. Secondary Outcome

Title	Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale
Description	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.
Time Frame	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]

Outcome Measure Data

Analysis Population Description

Randomized participants with non-missing FACT-L data both at baseline and at the specified cycle.

Arm/Group Title	Enzastaurin/Pemetrexed/Carboplatin	Pemetrexed/Carboplatin	Docetaxel/Carboplatin
Arm/Group Description	Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel 75 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Measure Participants	45	50	42
Cycle 1 (Week 3)	-3.98 (1.86)	1.12 (1.78)	-3.33 (1.88)
Cycle 2 (Week 6)	-3.25 (2.19)	-1.54 (2.08)	-2.16 (2.42)
Cycle 3 (Week 9)	0.39 (2.30)	0.64 (2.25)	-1.93 (2.49)
Cycle 4 (Week 12)	0.31 (2.47)	3.54 (2.23)	-0.81 (2.50)
Cycle 5 (Week 15)	1.89 (2.95)	-0.26 (2.57)	-4.69 (2.79)
Cycle 6 (Week 18)	7.38 (3.54)	-0.83 (2.84)	3.38 (3.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzastaurin/Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.96
	Comments	P-value is for the change in Total FACT-L at Cycle 1 (Week 3).
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments	P-value is for the change in Total FACT-L at Cycle 1 (Week 3).
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Enzastaurin/Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.92
	Comments	P-value is for the change in Total FACT-L at Cycle 2 (Week 6).
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.97
	Comments	P-value is for the change in Total FACT-L at Cycle 2 (Week 6).
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Enzastaurin/Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments	P-value is for the change in Total FACT-L at Cycle 3 (Week 9).
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments	P-value is for the change in Total FACT-L at Cycle 3 (Week 9).
	Method	ANCOVA
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Enzastaurin/Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.93
	Comments	P-value is for the change in Total FACT-L at Cycle 4 (Week 12).
	Method	ANCOVA
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments	P-value is for the change in Total FACT-L at Cycle 4 (Week 12).
	Method	ANCOVA
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Enzastaurin/Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.19
	Comments	P-value is for the change in Total FACT-L at Cycle 5 (Week 15).
	Method	ANCOVA
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.40
	Comments	P-value is for the change in Total FACT-L at Cycle 5 (Week 15).
	Method	ANCOVA
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Enzastaurin/Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.63
	Comments	P-value is for the change in Total FACT-L at Cycle 6 (Week 18).
	Method	ANCOVA
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.55
	Comments	P-value is for the change in Total FACT-L at Cycle 6 (Week 18).
	Method	ANCOVA
	Comments

6. Secondary Outcome

Title	Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale
Description	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.
Time Frame	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]

Outcome Measure Data

Analysis Population Description

Randomized participants with non-missing FACT-Taxane data both at baseline and at the specified cycle.

Arm/Group Title	Enzastaurin/Pemetrexed/Carboplatin	Pemetrexed/Carboplatin	Docetaxel/Carboplatin
Arm/Group Description	Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel 75 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Measure Participants	45	50	43
Cycle 1 (Week 3)	-3.16 (2.20)	-0.78 (2.08)	-2.17 (2.20)
Cycle 2 (Week 6)	-6.22 (2.90)	-5.66 (2.76)	-3.13 (3.16)
Cycle 3 (Week 9)	-1.89 (3.35)	-1.52 (3.32)	-4.40 (3.62)
Cycle 4 (Week 12)	-2.28 (3.65)	-0.77 (3.29)	-2.58 (3.74)
Cycle 5 (Week 15)	-2.52 (3.71)	-3.11 (3.24)	-7.74 (3.51)
Cycle 6 (Week 18)	2.77 (3.93)	-2.81 (3.26)	-0.34 (4.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzastaurin/Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.93
	Comments	P-value is for the change in Total FACT-Taxane at Cycle 1 (Week 3).
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.86
	Comments	P-value is for the change in Total FACT-Taxane at Cycle 1 (Week 3).
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Enzastaurin/Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.69
	Comments	P-value is for the change in Total FACT-Taxane at Cycle 2 (Week 6).
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.77
	Comments	P-value is for the change in Total FACT-Taxane at Cycle 2 (Week 6).
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Enzastaurin/Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments	P-value is for the change in Total FACT-Taxane at Cycle 3 (Week 9).
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.78
	Comments	P-value is for the change in Total FACT-Taxane at Cycle 3 (Week 9).
	Method	ANCOVA
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Enzastaurin/Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments	P-value is for the change in Total FACT-Taxane at Cycle 4 (Week 12).
	Method	ANCOVA
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.91
	Comments	P-value is for the change in Total FACT-Taxane at Cycle 4 (Week 12).
	Method	ANCOVA
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Enzastaurin/Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.49
	Comments	P-value is for the change in Total FACT-Taxane at Cycle 5 (Week 15).
	Method	ANCOVA
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.53
	Comments	P-value is for the change in Total FACT-Taxane at Cycle 5 (Week 15).
	Method	ANCOVA
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Enzastaurin/Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.80
	Comments	P-value is for the change in Total FACT-Taxane at Cycle 6 (Week 18).
	Method	ANCOVA
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.85
	Comments	P-value is for the change in Total FACT-Taxane at Cycle 6 (Week 18).
	Method	ANCOVA
	Comments

7. Secondary Outcome

Title	Overall Survival (OS)
Description	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.
Time Frame	Baseline to date of death from any cause up to 35 months

Outcome Measure Data

Analysis Population Description

All randomized participants. Sixteen (16) participants in Enzastaurin/Pemetrexed/Carboplatin group, 20 participants in Pemetrexed/Carboplatin group, and 19 participants in Docetaxel/Carboplatin group were censored for analysis.

Arm/Group Title	Enzastaurin/Pemetrexed/Carboplatin	Pemetrexed/Carboplatin	Docetaxel/Carboplatin
Arm/Group Description	Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel 75 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Measure Participants	56	54	53
Median (95% Confidence Interval) [months]	7.2	12.7	9.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzastaurin/Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.87
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	Log Rank
	Comments

8. Secondary Outcome

Title	Number of Participants With Complete Response (CR) or Partial Response (PR) [Tumor Response]
Description	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.
Time Frame	Baseline to measured PD up to 22.3 months

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	Enzastaurin/Pemetrexed/Carboplatin	Pemetrexed/Carboplatin	Docetaxel/Carboplatin
Arm/Group Description	Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel 75 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Measure Participants	72	74	72
Count of Participants [Participants]	9 12.5%	16 21.6%	19 26.4%

9. Secondary Outcome

Title	Duration of CR or PR (Duration of Response)
Description	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.
Time Frame	Date of first response to the date of progression or death due to any cause up to 22.3 months

Outcome Measure Data

Analysis Population Description

All randomized participants. 63 participants in Enzastaurin/Pemetrexed/Carboplatin group, 58 participants in Pemetrexed/Carboplatin group, and 53 participants in Docetaxel/Carboplatin group were censored for analysis.

Arm/Group Title	Enzastaurin/Pemetrexed/Carboplatin	Pemetrexed/Carboplatin	Docetaxel/Carboplatin
Arm/Group Description	Enzastaurin loading dose of 1125 mg or 1200 mg on Day -7 (pre-chemotherapy) followed by 500 mg administered once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel 75 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Measure Participants	9	16	19
Median (95% Confidence Interval) [months]	7.4	9.3	5.8

10. Secondary Outcome

Title	Time-to-Treatment Failure (TTF)
Description	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.
Time Frame	Baseline to stopping treatment up to 14.1 months

Outcome Measure Data

Analysis Population Description

All randomized participants. Thirty four (34) participants in Pemetrexed/Carboplatin group and 23 participants in Docetaxel/Carboplatin group were censored for analysis. No participants were censored in Enzastaurin/Pemetrexed/Carboplatin group.

Arm/Group Title	Enzastaurin/Pemetrexed/Carboplatin	Pemetrexed/Carboplatin	Docetaxel/Carboplatin
Arm/Group Description	Enzastaurin loading dose of 1125 mg or 1200 mg orally on Day -7 (pre-chemotherapy) followed by 500 mg administered orally once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.	Docetaxel 75 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
Measure Participants	38	51	72
Median (95% Confidence Interval) [months]	2.6	3.8	2.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzastaurin/Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed/Carboplatin, Docetaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	Log Rank
	Comments

Adverse Events

Adverse Event Reporting Description	Study-specific clinical outcomes due to PD were not considered to be a SAE unless the investigator deemed it related to the use of the study drug.
Arm/Group Title	Enzastaurin/Pemetrexed/Carboplatin		Pemetrexed/Carboplatin		Docetaxel/Carboplatin
Arm/Group Description	Enzastaurin loading dose of 1125 mg or 1200 mg on Day -7 (pre-chemotherapy) followed by 500 mg administered once daily starting from Day -6 until disease progression. Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.		Pemetrexed 500 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.		Docetaxel 75 mg/m^2 and carboplatin AUC 6 mg*min/mL as an intravenous infusion on Day 1 every 21 days for a maximum of 6 cycles (21-day cycle) or disease progression whichever came first.
All Cause Mortality
	Enzastaurin/Pemetrexed/Carboplatin		Pemetrexed/Carboplatin		Docetaxel/Carboplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Enzastaurin/Pemetrexed/Carboplatin		Pemetrexed/Carboplatin		Docetaxel/Carboplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/67 (52.2%)		20/72 (27.8%)		26/70 (37.1%)
Blood and lymphatic system disorders
Febrile neutropenia	1/67 (1.5%)	1	1/72 (1.4%)	1	6/70 (8.6%)	8
Cardiac disorders
Arrhythmia	3/67 (4.5%)	3	1/72 (1.4%)	2	1/70 (1.4%)	1
Cardio-respiratory arrest	1/67 (1.5%)	1	1/72 (1.4%)	1	0/70 (0%)	0
Myocardial infarction	0/67 (0%)	0	1/72 (1.4%)	1	1/70 (1.4%)	1
Pericardial effusion	1/67 (1.5%)	1	0/72 (0%)	0	1/70 (1.4%)	1
Gastrointestinal disorders
Abdominal pain	1/67 (1.5%)	1	0/72 (0%)	0	0/70 (0%)	0
Caecitis	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Diarrhoea	1/67 (1.5%)	1	1/72 (1.4%)	1	3/70 (4.3%)	3
Duodenal ulcer	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Dysphagia	0/67 (0%)	0	1/72 (1.4%)	1	0/70 (0%)	0
Enteritis	2/67 (3%)	2	1/72 (1.4%)	1	0/70 (0%)	0
Impaired gastric emptying	0/67 (0%)	0	1/72 (1.4%)	1	0/70 (0%)	0
Lower gastrointestinal haemorrhage	1/67 (1.5%)	1	0/72 (0%)	0	1/70 (1.4%)	1
Nausea	1/67 (1.5%)	2	1/72 (1.4%)	1	0/70 (0%)	0
Rectal haemorrhage	1/67 (1.5%)	1	0/72 (0%)	0	0/70 (0%)	0
Stomatitis	1/67 (1.5%)	1	0/72 (0%)	0	0/70 (0%)	0
Vomiting	1/67 (1.5%)	2	1/72 (1.4%)	1	1/70 (1.4%)	1
General disorders
Chest pain	3/67 (4.5%)	3	0/72 (0%)	0	0/70 (0%)	0
Disease progression	0/67 (0%)	0	1/72 (1.4%)	1	0/70 (0%)	0
Fatigue	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Localised oedema	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Oedema due to cardiac disease	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Pain	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Pyrexia	1/67 (1.5%)	1	0/72 (0%)	0	1/70 (1.4%)	1
Infections and infestations
Abdominal infection	0/67 (0%)	0	1/72 (1.4%)	1	0/70 (0%)	0
Cellulitis	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Pneumonia	7/67 (10.4%)	8	3/72 (4.2%)	3	2/70 (2.9%)	3
Sepsis	2/67 (3%)	2	0/72 (0%)	0	4/70 (5.7%)	4
Injury, poisoning and procedural complications
Fall	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Fracture	2/67 (3%)	2	2/72 (2.8%)	2	1/70 (1.4%)	1
Investigations
Aspartate aminotransferase	1/67 (1.5%)	1	0/72 (0%)	0	0/70 (0%)	0
Blood bilirubin	1/67 (1.5%)	1	0/72 (0%)	0	0/70 (0%)	0
Blood calcium decreased	1/67 (1.5%)	1	1/72 (1.4%)	1	0/70 (0%)	0
Blood creatinine	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Blood potassium decreased	3/67 (4.5%)	3	0/72 (0%)	0	0/70 (0%)	0
Blood sodium decreased	1/67 (1.5%)	1	0/72 (0%)	0	1/70 (1.4%)	1
Haemoglobin	4/67 (6%)	4	3/72 (4.2%)	3	2/70 (2.9%)	2
Neutrophil count	1/67 (1.5%)	1	0/72 (0%)	0	3/70 (4.3%)	3
Platelet count	1/67 (1.5%)	1	0/72 (0%)	0	0/70 (0%)	0
White blood cell count	3/67 (4.5%)	3	0/72 (0%)	0	0/70 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Dehydration	4/67 (6%)	4	1/72 (1.4%)	1	5/70 (7.1%)	5
Electrolyte imbalance	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Hyperglycaemia	1/67 (1.5%)	1	0/72 (0%)	0	0/70 (0%)	0
Musculoskeletal and connective tissue disorders
Bone pain	1/67 (1.5%)	1	0/72 (0%)	0	0/70 (0%)	0
Muscular weakness	5/67 (7.5%)	6	0/72 (0%)	0	3/70 (4.3%)	4
Myalgia	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Pain in extremity	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer recurrent	1/67 (1.5%)	1	0/72 (0%)	0	0/70 (0%)	0
Nervous system disorders
Cerebral ischaemia	1/67 (1.5%)	1	3/72 (4.2%)	3	1/70 (1.4%)	1
Convulsion	0/67 (0%)	0	1/72 (1.4%)	1	0/70 (0%)	0
Dizziness	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Syncope	1/67 (1.5%)	1	0/72 (0%)	0	1/70 (1.4%)	1
Psychiatric disorders
Confusional state	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Mental status changes	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Renal and urinary disorders
Renal failure	2/67 (3%)	2	0/72 (0%)	0	0/70 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	4/67 (6%)	4	2/72 (2.8%)	2	2/70 (2.9%)	2
Hypoxia	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Lung infiltration	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Orthopnoea	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Pleural effusion	1/67 (1.5%)	1	1/72 (1.4%)	1	3/70 (4.3%)	3
Pneumothorax	1/67 (1.5%)	1	0/72 (0%)	0	0/70 (0%)	0
Pulmonary embolism	2/67 (3%)	2	2/72 (2.8%)	2	3/70 (4.3%)	3
Pulmonary fibrosis	1/67 (1.5%)	1	0/72 (0%)	0	0/70 (0%)	0
Respiratory failure	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Respiratory tract haemorrhage	0/67 (0%)	0	1/72 (1.4%)	1	0/70 (0%)	0
Skin and subcutaneous tissue disorders
Hyperhidrosis	0/67 (0%)	0	0/72 (0%)	0	1/70 (1.4%)	1
Vascular disorders
Aortic thrombosis	1/67 (1.5%)	1	0/72 (0%)	0	0/70 (0%)	0
Deep vein thrombosis	2/67 (3%)	2	0/72 (0%)	0	1/70 (1.4%)	1
Embolism	1/67 (1.5%)	1	0/72 (0%)	0	0/70 (0%)	0
Haematoma	1/67 (1.5%)	1	0/72 (0%)	0	0/70 (0%)	0
Haemorrhage	0/67 (0%)	0	1/72 (1.4%)	1	0/70 (0%)	0
Hypotension	2/67 (3%)	2	0/72 (0%)	0	1/70 (1.4%)	1
Thrombosis	1/67 (1.5%)	1	0/72 (0%)	0	0/70 (0%)	0
Other (Not Including Serious) Adverse Events
	Enzastaurin/Pemetrexed/Carboplatin		Pemetrexed/Carboplatin		Docetaxel/Carboplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	63/67 (94%)		70/72 (97.2%)		69/70 (98.6%)
Blood and lymphatic system disorders
Lymphopenia	0/67 (0%)	0	4/72 (5.6%)	15	4/70 (5.7%)	8
Cardiac disorders
Arrhythmia	3/67 (4.5%)	4	4/72 (5.6%)	4	4/70 (5.7%)	4
Eye disorders
Dry eye	4/67 (6%)	4	0/72 (0%)	0	0/70 (0%)	0
Lacrimation increased	4/67 (6%)	6	3/72 (4.2%)	3	2/70 (2.9%)	2
Gastrointestinal disorders
Abdominal pain	9/67 (13.4%)	9	5/72 (6.9%)	6	6/70 (8.6%)	8
Constipation	17/67 (25.4%)	22	25/72 (34.7%)	26	17/70 (24.3%)	19
Diarrhoea	18/67 (26.9%)	29	10/72 (13.9%)	12	19/70 (27.1%)	23
Dyspepsia	6/67 (9%)	6	2/72 (2.8%)	2	7/70 (10%)	7
Nausea	34/67 (50.7%)	57	32/72 (44.4%)	52	24/70 (34.3%)	40
Stomatitis	6/67 (9%)	6	14/72 (19.4%)	16	13/70 (18.6%)	15
Vomiting	16/67 (23.9%)	23	18/72 (25%)	20	15/70 (21.4%)	19
General disorders
Chest pain	9/67 (13.4%)	12	13/72 (18.1%)	15	8/70 (11.4%)	8
Fatigue	28/67 (41.8%)	46	39/72 (54.2%)	55	35/70 (50%)	63
Localised oedema	2/67 (3%)	5	5/72 (6.9%)	5	2/70 (2.9%)	2
Oedema peripheral	9/67 (13.4%)	10	14/72 (19.4%)	16	7/70 (10%)	8
Pyrexia	5/67 (7.5%)	5	8/72 (11.1%)	8	7/70 (10%)	8
Immune system disorders
Hypersensitivity	1/67 (1.5%)	1	0/72 (0%)	0	6/70 (8.6%)	10
Infections and infestations
Rhinitis	2/67 (3%)	4	7/72 (9.7%)	10	3/70 (4.3%)	3
Vaginal infection	2/28 (7.1%)	3	1/32 (3.1%)	1	0/29 (0%)	0
Investigations
Alanine aminotransferase	3/67 (4.5%)	4	9/72 (12.5%)	10	1/70 (1.4%)	1
Aspartate aminotransferase	3/67 (4.5%)	4	4/72 (5.6%)	7	2/70 (2.9%)	2
Blood albumin decreased	2/67 (3%)	2	6/72 (8.3%)	10	6/70 (8.6%)	7
Blood alkaline phosphatase	3/67 (4.5%)	3	2/72 (2.8%)	2	4/70 (5.7%)	11
Blood creatinine	2/67 (3%)	2	7/72 (9.7%)	9	4/70 (5.7%)	4
Blood magnesium decreased	2/67 (3%)	3	7/72 (9.7%)	8	3/70 (4.3%)	3
Blood potassium decreased	6/67 (9%)	9	8/72 (11.1%)	10	6/70 (8.6%)	8
Blood potassium increased	2/67 (3%)	2	4/72 (5.6%)	5	3/70 (4.3%)	3
Blood sodium decreased	6/67 (9%)	6	6/72 (8.3%)	7	4/70 (5.7%)	6
Haemoglobin	40/67 (59.7%)	99	53/72 (73.6%)	132	34/70 (48.6%)	59
Neutrophil count	33/67 (49.3%)	88	37/72 (51.4%)	114	46/70 (65.7%)	138
Platelet count	37/67 (55.2%)	116	43/72 (59.7%)	151	18/70 (25.7%)	41
Weight decreased	7/67 (10.4%)	7	5/72 (6.9%)	5	2/70 (2.9%)	2
White blood cell count	23/67 (34.3%)	63	29/72 (40.3%)	99	21/70 (30%)	65
Metabolism and nutrition disorders
Decreased appetite	12/67 (17.9%)	16	12/72 (16.7%)	13	19/70 (27.1%)	27
Dehydration	14/67 (20.9%)	15	6/72 (8.3%)	6	8/70 (11.4%)	8
Hyperglycaemia	3/67 (4.5%)	9	13/72 (18.1%)	32	7/70 (10%)	7
Musculoskeletal and connective tissue disorders
Arthralgia	6/67 (9%)	9	5/72 (6.9%)	8	7/70 (10%)	8
Back pain	3/67 (4.5%)	3	12/72 (16.7%)	14	6/70 (8.6%)	7
Muscular weakness	12/67 (17.9%)	16	9/72 (12.5%)	10	10/70 (14.3%)	11
Myalgia	0/67 (0%)	0	2/72 (2.8%)	3	5/70 (7.1%)	5
Pain in extremity	4/67 (6%)	5	7/72 (9.7%)	7	5/70 (7.1%)	8
Nervous system disorders
Dizziness	12/67 (17.9%)	14	6/72 (8.3%)	8	7/70 (10%)	7
Dysgeusia	6/67 (9%)	7	7/72 (9.7%)	7	14/70 (20%)	15
Headache	5/67 (7.5%)	5	5/72 (6.9%)	5	4/70 (5.7%)	4
Peripheral sensory neuropathy	8/67 (11.9%)	8	9/72 (12.5%)	10	13/70 (18.6%)	14
Syncope	4/67 (6%)	4	0/72 (0%)	0	0/70 (0%)	0
Psychiatric disorders
Anxiety	4/67 (6%)	4	5/72 (6.9%)	5	4/70 (5.7%)	5
Depressed mood	2/67 (3%)	2	5/72 (6.9%)	5	5/70 (7.1%)	5
Insomnia	8/67 (11.9%)	8	8/72 (11.1%)	8	14/70 (20%)	15
Renal and urinary disorders
Pollakiuria	0/67 (0%)	0	4/72 (5.6%)	4	1/70 (1.4%)	1
Reproductive system and breast disorders
Erectile dysfunction	0/39 (0%)	0	2/40 (5%)	2	1/41 (2.4%)	1
Respiratory, thoracic and mediastinal disorders
Cough	7/67 (10.4%)	8	17/72 (23.6%)	19	12/70 (17.1%)	15
Dyspnoea	15/67 (22.4%)	17	16/72 (22.2%)	19	13/70 (18.6%)	16
Oropharyngeal pain	2/67 (3%)	3	5/72 (6.9%)	5	3/70 (4.3%)	3
Respiratory tract haemorrhage	5/67 (7.5%)	8	5/72 (6.9%)	6	3/70 (4.3%)	3
Skin and subcutaneous tissue disorders
Alopecia	4/67 (6%)	4	6/72 (8.3%)	6	20/70 (28.6%)	22
Dry skin	5/67 (7.5%)	5	2/72 (2.8%)	2	3/70 (4.3%)	3
Exfoliative rash	7/67 (10.4%)	9	15/72 (20.8%)	15	5/70 (7.1%)	5
Pruritus	3/67 (4.5%)	3	7/72 (9.7%)	7	3/70 (4.3%)	4
Vascular disorders
Hypotension	7/67 (10.4%)	7	1/72 (1.4%)	1	1/70 (1.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.