A Study of Irinotecan Plus Cetuximab With or Without Enza... | NCT00437268

ID	Type	Description	Link
H6Q-MC-S018	Other Identifier	Eli Lilly and Company

Label	Type	Description	Intervention Names
enzastaurin + irinotecan + cetuximab	Experimental		Drug: enzastaurin Drug: irinotecan Drug: cetuximab
irinotecan + cetuximab	Active Comparator		Drug: irinotecan Drug: cetuximab

Name	Type	Description	Arm Group Labels	Other Names
enzastaurin	Drug	1125 milligrams (mg) loading dose, then 500 mg orally, daily, of each 21-day cycle until progressive disease	enzastaurin + irinotecan + cetuximab

Measure	Description	Time Frame
Percentage of Participants With Progression-Free Survival (PFS) at 6 Months (PFS Rate)	PFS was defined as the time from the date of study enrollment to the first date of progressive disease or death from any cause. For participants not known to have died as of the data cut-off date and who did not have progressive disease, PFS was censored at the date of last visit with adequate assessment. For participants who received subsequent anticancer therapy (after discontinuation from the study treatment) prior to disease progression or death, PFS was censored at the date of last visit with adequate assessment prior to the initiation of post-discontinuation anticancer therapy. The PFS probability values were multiplied by 100 to obtain the percentage values.	At 6 months from randomization

Measure	Description	Time Frame
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Tumor Response Rate)	Tumor response rate was defined as number of participants with overall best response of complete response (CR) or partial response (PR) over number of protocol qualified participants using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0) Guidelines. CR was defined as the disappearance of all tumor lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum of LDs or complete disappearance of target lesions, with persistence (but not worsening) of 1 or more non-target lesions, with no new lesions appearing. Percentage of participants = (Number of participants with overall best response of CR or PR/Number of protocol qualified participants) x 100.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participants are eligible to be included in the study only if they meet all of the following criteria:

Histologic diagnosis of colorectal cancer.
Performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) performance status schedule.
Have had documented disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST v1.0; Therasse et al. 2000) within 3 months after receiving 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus bevacizumab as first-line therapy for locally advanced or metastatic disease, or within 6 months after receiving FOLFOX with or without bevacizumab in the adjuvant setting.
Standard radiation therapy for rectal cancer is allowed. Participants must have recovered from the toxic effects (except for alopecia) of the treatment prior to study enrollment. Prior radiotherapy must be completed 4 weeks before study entry. Lesions that have been radiated in the advanced setting cannot be included as sites of measurable disease unless clear tumor progression has been documented in these lesions since the end of radiation therapy.
At least one uni-dimensionally measurable lesion meeting RECIST v1.0 guidelines (at least 10 millimeters [mm] in longest diameter by spiral computerized tomography (CT) scan, or at least 20 mm by standard techniques). Positron emission tomography (PET) scans and ultrasounds may not be used.

Exclusion Criteria:

Participants will be excluded from the study if they meet any of the following criteria:

Have received treatment within the last 4 weeks with a drug that has not received regulatory approval for any indication at the time of study entry.
Have previously completed or withdrawn from this study or any other study investigating enzastaurin, irinotecan, or cetuximab.
Have a serious concomitant systemic disorder [such as active infection including human immunodeficiency virus (HIV), or cardiac disease] that, in the opinion of the investigator, would compromise the participant's ability to adhere to the protocol.
Have a serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV.
Have a prior malignancy (other than colorectal cancer, or adequately treated carcinoma in-situ of the cervix or nonmelanoma skin cancer), unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence. Participants with a history of low grade (Gleason score less than or equal to 6) localized prostate cancer will be eligible even if diagnosed less than 5 years previously.

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

Facility	Status	City	State	ZIP	Country	Contacts
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.		Casa Grande	Arizona	85222

ID	Title	Description
FG000	Enzastaurin+Irinotecan+Cetuximab	Enzastaurin: 1125 milligrams (mg) loading dose on Day 1 of Cycle 1, then 500 mg orally, daily, of each 21-day cycle until progressive disease Irinotecan: 300 milligrams per square meter (mg/m^2), intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m^2 intravenously on Day 1, then 250 mg/m^2 on Days 8 and 15 of Cycle 1, then 250 mg/m^2 on Days 8 and 15 in Cycle 1, then 250 mg/m^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease

ID	Title	Description
BG000	Enzastaurin+Irinotecan+Cetuximab	Enzastaurin: 1125 milligrams (mg) loading dose on Day 1 of Cycle 1, then 500 mg orally, daily, of each 21-day cycle until progressive disease Irinotecan: 300 mg/m^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m^2 intravenously on Day 1, then 250 mg/m^2 on Days 8 and 15 in Cycle 1, then 250 mg/m^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease
BG001	Irinotecan+Cetuximab	Irinotecan: 300 mg/m^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m^2 intravenously on Day 1, then 250 mg/m^2 on Days 8 and 15 in Cycle 1, then 250 mg/m^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00013 BG00113 BG00226

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Progression-Free Survival (PFS) at 6 Months (PFS Rate)

PFS was defined as the time from the date of study enrollment to the first date of progressive disease or death from any cause. For participants not known to have died as of the data cut-off date and who did not have progressive disease, PFS was censored at the date of last visit with adequate assessment. For participants who received subsequent anticancer therapy (after discontinuation from the study treatment) prior to disease progression or death, PFS was censored at the date of last visit with adequate assessment prior to the initiation of post-discontinuation anticancer therapy. The PFS probability values were multiplied by 100 to obtain the percentage values.

Protocol qualified population: All randomized participants who received at least 1 dose of study drug and did not develop a severe infusion reaction to cetuximab after the first dose. Participants censored: Irinotecan +Cetuximab+Enzastaurin = 1; Irinotecan +Cetuximab =2.

Posted

Number

95% Confidence Interval

percentage of participants

At 6 months from randomization

ID	Title	Description
OG000	Enzastaurin+Irinotecan+Cetuximab	Enzastaurin: 1125 milligrams (mg) loading dose on Day 1 of Cycle 1, then 500 mg orally, daily, of each 21-day cycle until progressive disease Irinotecan: 300 mg/m^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m^2 intravenously on Day 1, then 250 mg/m^2 on Days 8 and 15 in Cycle 1, then 250 mg/m^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease
OG001	Irinotecan+Cetuximab	Irinotecan: 300 mg/m^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m^2 intravenously on Day 1, then 250 mg/m^2 on Days 8 and 15 in Cycle 1, then 250 mg/m^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease

Units	Counts
Participants	OG00013 OG00112

Title

Denominators

Categories

Title	Measurements
	OG00026(1 to 51) OG00123(0 to 49)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.431	The type 1 error rate was set at 0.20													Superiority or Other (legacy)

Secondary

Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Tumor Response Rate)

Tumor response rate was defined as number of participants with overall best response of complete response (CR) or partial response (PR) over number of protocol qualified participants using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0) Guidelines. CR was defined as the disappearance of all tumor lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum of LDs or complete disappearance of target lesions, with persistence (but not worsening) of 1 or more non-target lesions, with no new lesions appearing. Percentage of participants = (Number of participants with overall best response of CR or PR/Number of protocol qualified participants) x 100.

Protocol qualified population: All randomized participants who received at least 1 dose of study drug and did not develop a severe infusion reaction to cetuximab after the first dose.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline to measured progressive disease up to 13.2 months

ID	Title	Description
OG000	Enzastaurin+Irinotecan+Cetuximab	Enzastaurin: 1125 milligrams (mg) loading dose on Day 1 of Cycle 1, then 500 mg orally, daily, of each 21-day cycle until progressive disease Irinotecan: 300 mg/m^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m^2 intravenously on Day 1, then 250 mg/m^2 on Days 8 and 15 in Cycle 1, then 250 mg/m^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease

Secondary

Duration of Response

The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of disease progression or death from any cause. According to the Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria, CR was defined as the disappearance of all tumor lesions and PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum of LDs or complete disappearance of target lesions, with persistence (but not worsening) of 1 or more non-target lesions, with no new lesions appearing. For participants who died, the duration of response was censored at death. For participants still alive, duration of response was censored at the last visit with adequate assessment.

Participants with a CR or PR. No participants were censored.

Posted

Median

95% Confidence Interval

months

Time of response to progressive disease up to 13.2 months

ID	Title	Description
OG000	Enzastaurin+Irinotecan+Cetuximab	Enzastaurin: 1125 milligrams (mg) loading dose on Day 1 of Cycle 1, then 500 mg orally, daily, of each 21-day cycle until progressive disease Irinotecan: 300 milligrams per square meter (mg/m^2), intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m^2 intravenously on Day 1, then 250 mg/m^2 on Days 8 and 15 of Cycle 1, then 250 mg/m^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease
OG001	Irinotecan+Cetuximab

Secondary

Overall Survival (OS)

OS was defined as the time in months from the date of study enrollment to the date of death from any cause. For participants not known to have died as of the cut-off date, OS was censored at the last contact date.

Protocol qualified population: All randomized participants who received at least 1 dose of study drug and did not develop a severe infusion reaction to cetuximab after the first dose. Censored participants: Enzastaurin+Irinotecan+Cetuximab = 4; Irinotecan+Cetuximab = 4.

Posted

Median

95% Confidence Interval

months

Randomization to date of death from any cause up to 21.9 months

ID	Title	Description
OG000	Enzastaurin+Irinotecan+Cetuximab	Enzastaurin: 1125 milligrams (mg) loading dose on Day 1 of Cycle 1, then 500 mg orally, daily, of each 21-day cycle until progressive disease Irinotecan: 300 mg/m^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m^2 intravenously on Day 1, then 250 mg/m^2 on Days 8 and 15 in Cycle 1, then 250 mg/m^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease
OG001	Irinotecan+Cetuximab	Irinotecan: 300 mg/m^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m^2 intravenously on Day 1, then 250 mg/m^2 on Days 8 and 15 in Cycle 1, then 250 mg/m^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease

Secondary

Percentage of Participants With a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate)

The overall disease control rate for each treatment arm was calculated as percent of participants with overall response of complete response (CR), partial response (PR) or stable disease (SD) over number of protocol qualified population. According to the Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria, CR was defined as the disappearance of all tumor lesions, PR was defined as at least a 30% decrease in sum of longest diameter (LD) of target lesions, progressive disease (PD) was defined as at least 20% increase in sum of LD of target lesions, and SD was defined as small changes that did not meet above criteria.

Percentage of participants = (Number of participants with overall best response of CR, PR, or SD/Number of protocol qualified participants) x 100.

Protocol qualified population: All randomized participants who received at least 1 dose of study drug and did not develop a severe infusion reaction to cetuximab after the first dose.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline to disease progression (up to 13.2 months)

ID	Title	Description
OG000	Enzastaurin+Irinotecan+Cetuximab	Enzastaurin: 1125 milligrams (mg) loading dose on Day 1 of Cycle 1, then 500 mg orally, daily, of each 21-day cycle until progressive disease Irinotecan: 300 mg/m^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m^2 intravenously on Day 1, then 250 mg/m^2 on Days 8 and 15 in Cycle 1, then 250 mg/m^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease

Secondary

Number of Participants With Adverse Events (AEs) or Who Died

Clinically significant events were defined as serious and other non-serious AEs. Participants who died due to progressive disease (PD) or and adverse events (AEs) while on treatment and or died during the 30 day post-treatment are included. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

The safety population included all randomized and treated participants.

Posted

Count of Participants

Participants

Baseline to study completion (Cycle 31.5 [21 days/cycle] and 30-day safety follow-up)

ID	Title	Description
OG000	Enzastaurin+Irinotecan+Cetuximab	Enzastaurin: 1125 milligrams (mg) loading dose on Day 1 of Cycle 1, then 500 mg orally, daily, of each 21-day cycle until progressive disease Irinotecan: 300 mg/m^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m^2 intravenously on Day 1, then 250 mg/m^2 on Days 8 and 15 in Cycle 1, then 250 mg/m^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease
OG001	Irinotecan+Cetuximab	Irinotecan: 300 mg/m^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m^2 intravenously on Day 1, then 250 mg/m^2 on Days 8 and 15 in Cycle 1, then 250 mg/m^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Febrile neutropenia	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG0002 events2 affected13 at risk EG0011 events1 affected13 at risk
Neutropenia	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG0003 events2 affected13 at risk EG0010 events0 affected13 at risk
Pancytopenia	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Abdominal pain	Gastrointestinal disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0012 events2 affected13 at risk
Ascites	Gastrointestinal disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Diarrhoea	Gastrointestinal disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Nausea	Gastrointestinal disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Rectal haemorrhage	Gastrointestinal disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Small intestinal obstruction	Gastrointestinal disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0011 events1 affected13 at risk
Vomiting	Gastrointestinal disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Fatigue	General disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Multi-organ failure	General disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Gallbladder obstruction	Hepatobiliary disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Anorectal cellulitis	Infections and infestations	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Bacteraemia	Infections and infestations	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Clostridium difficile colitis	Infections and infestations	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Rib fracture	Injury, poisoning and procedural complications	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Dehydration	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Hyperkalaemia	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Hypoglycaemia	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Mental status changes	Psychiatric disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	16.0	Systematic Assessment	EG0001 events1 affected9 at risk EG0011 events1 affected9 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Hypotension	Vascular disorders	16.0	Systematic Assessment	EG0002 events1 affected13 at risk EG0010 events0 affected13 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG0003 events3 affected13 at risk EG0014 events4 affected13 at risk
Leukopenia	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG0002 events2 affected13 at risk EG0016 events3 affected13 at risk
Neutropenia	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG0007 events5 affected13 at risk EG00110 events5 affected13 at risk
Thrombocytopenia	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG0004 events1 affected13 at risk EG0010 events0 affected13 at risk
Ear discomfort	Ear and labyrinth disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Vertigo	Ear and labyrinth disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Erythema of eyelid	Eye disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Eye irritation	Eye disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Abdominal discomfort	Gastrointestinal disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Abdominal distension	Gastrointestinal disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0014 events4 affected13 at risk
Abdominal pain	Gastrointestinal disorders	16.0	Systematic Assessment	EG0003 events3 affected13 at risk EG0016 events6 affected13 at risk
Abdominal pain upper	Gastrointestinal disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Ascites	Gastrointestinal disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0011 events1 affected13 at risk
Breath odour	Gastrointestinal disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Colitis	Gastrointestinal disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Constipation	Gastrointestinal disorders	16.0	Systematic Assessment	EG0008 events4 affected13 at risk EG0012 events2 affected13 at risk
Diarrhoea	Gastrointestinal disorders	16.0	Systematic Assessment	EG00011 events8 affected13 at risk EG00118 events9 affected13 at risk
Dry mouth	Gastrointestinal disorders	16.0	Systematic Assessment	EG0005 events4 affected13 at risk EG0012 events2 affected13 at risk
Dyspepsia	Gastrointestinal disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Dysphagia	Gastrointestinal disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Flatulence	Gastrointestinal disorders	16.0	Systematic Assessment	EG0002 events2 affected13 at risk EG0010 events0 affected13 at risk
Haemorrhoids	Gastrointestinal disorders	16.0	Systematic Assessment	EG0002 events2 affected13 at risk EG0010 events0 affected13 at risk
Nausea	Gastrointestinal disorders	16.0	Systematic Assessment	EG00010 events8 affected13 at risk EG00120 events11 affected13 at risk
Oral pain	Gastrointestinal disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Rectal haemorrhage	Gastrointestinal disorders	16.0	Systematic Assessment	EG0002 events1 affected13 at risk EG0012 events2 affected13 at risk
Stomatitis	Gastrointestinal disorders	16.0	Systematic Assessment	EG0003 events3 affected13 at risk EG0011 events1 affected13 at risk
Vomiting	Gastrointestinal disorders	16.0	Systematic Assessment	EG0005 events5 affected13 at risk EG0017 events6 affected13 at risk
Asthenia	General disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0014 events3 affected13 at risk
Chills	General disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0011 events1 affected13 at risk
Cyst	General disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Fatigue	General disorders	16.0	Systematic Assessment	EG0009 events8 affected13 at risk EG00113 events9 affected13 at risk
Influenza like illness	General disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Non-cardiac chest pain	General disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Oedema peripheral	General disorders	16.0	Systematic Assessment	EG0002 events1 affected13 at risk EG0012 events2 affected13 at risk
Pain	General disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Pyrexia	General disorders	16.0	Systematic Assessment	EG0002 events2 affected13 at risk EG0010 events0 affected13 at risk
Xerosis	General disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Abscess limb	Infections and infestations	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Candidiasis	Infections and infestations	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Localised infection	Infections and infestations	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Nasopharyngitis	Infections and infestations	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Rash pustular	Infections and infestations	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Rectal abscess	Infections and infestations	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Rhinitis	Infections and infestations	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Sinusitis	Infections and infestations	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Upper respiratory tract infection	Infections and infestations	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Contusion	Injury, poisoning and procedural complications	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Sunburn	Injury, poisoning and procedural complications	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Alanine aminotransferase increased	Investigations	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0011 events1 affected13 at risk
Aspartate aminotransferase increased	Investigations	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0011 events1 affected13 at risk
Blood alkaline phosphatase increased	Investigations	16.0	Systematic Assessment	EG0002 events2 affected13 at risk EG0011 events1 affected13 at risk
Blood creatinine increased	Investigations	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Blood lactate dehydrogenase increased	Investigations	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Blood pressure increased	Investigations	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Blood urea increased	Investigations	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Carcinoembryonic antigen increased	Investigations	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0011 events1 affected13 at risk
Haemoglobin decreased	Investigations	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Liver function test abnormal	Investigations	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0012 events1 affected13 at risk
Neutrophil count decreased	Investigations	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Platelet count decreased	Investigations	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Weight decreased	Investigations	16.0	Systematic Assessment	EG0002 events2 affected13 at risk EG0012 events2 affected13 at risk
Weight increased	Investigations	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Decreased appetite	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG0004 events4 affected13 at risk EG0017 events6 affected13 at risk
Dehydration	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0013 events3 affected13 at risk
Hypercalcaemia	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Hyperkalaemia	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG0004 events1 affected13 at risk EG0010 events0 affected13 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Hypocalcaemia	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Hypoglycaemia	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Hypokalaemia	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG0003 events2 affected13 at risk EG0019 events4 affected13 at risk
Hyponatraemia	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Iron deficiency	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Back pain	Musculoskeletal and connective tissue disorders	16.0	Systematic Assessment	EG0004 events4 affected13 at risk EG0014 events4 affected13 at risk
Flank pain	Musculoskeletal and connective tissue disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0012 events2 affected13 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Haemangioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Oral neoplasm benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Dizziness	Nervous system disorders	16.0	Systematic Assessment	EG0005 events5 affected13 at risk EG0012 events2 affected13 at risk
Headache	Nervous system disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0012 events2 affected13 at risk
Peripheral sensory neuropathy	Nervous system disorders	16.0	Systematic Assessment	EG0002 events2 affected13 at risk EG0010 events0 affected13 at risk
Anxiety	Psychiatric disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Depression	Psychiatric disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Insomnia	Psychiatric disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0011 events1 affected13 at risk
Chromaturia	Renal and urinary disorders	16.0	Systematic Assessment	EG0003 events3 affected13 at risk EG0010 events0 affected13 at risk
Haematuria	Renal and urinary disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Pollakiuria	Renal and urinary disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Urinary bladder haemorrhage	Renal and urinary disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Urinary retention	Renal and urinary disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Cough	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0011 events1 affected13 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0002 events2 affected13 at risk EG0011 events1 affected13 at risk
Hyperventilation	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Rhinalgia	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0002 events1 affected13 at risk EG0010 events0 affected13 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Acne	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Alopecia	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG0004 events4 affected13 at risk EG0015 events5 affected13 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG0007 events6 affected13 at risk EG0017 events7 affected13 at risk
Drug eruption	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG0002 events2 affected13 at risk EG0010 events0 affected13 at risk
Dry skin	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG0003 events3 affected13 at risk EG0012 events2 affected13 at risk
Exfoliative rash	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0012 events1 affected13 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0011 events1 affected13 at risk
Nail disorder	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Night sweats	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Onychoclasis	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Petechiae	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected13 at risk
Pruritus	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG0001 events1 affected13 at risk EG0013 events3 affected13 at risk
Rash	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG0009 events5 affected13 at risk EG0016 events5 affected13 at risk
Skin exfoliation	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Skin fissures	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk
Hypotension	Vascular disorders	16.0	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected13 at risk

ID	Term
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D003108	Colonic Diseases
D007410	Intestinal Diseases
D012002	Rectal Diseases

ID	Term
D002166	Camptothecin
D000470	Alkaloids
D006571	Heterocyclic Compounds
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Enzastaurin+Irinotecan+Cetuximab	Enzastaurin: 1125 milligrams (mg) loading dose on Day 1 of Cycle 1, then 500 mg orally, daily, of each 21-day cycle until progressive disease Irinotecan: 300 milligrams per square meter (mg/m^2), intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m^2 intravenously on Day 1, then 250 mg/m^2 on Days 8 and 15 of Cycle 1, then 250 mg/m^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease			8	13	13	13
EG001	Irinotecan+Cetuximab	Irinotecan: 300 mg/m^2 intravenously on Day 1 of each 21-day cycle until progressive disease Cetuximab: 400 mg/m^2 intravenously on Day 1, then 250 mg/m^2 on Days 8 and 15 in Cycle 1, then 250 mg/m^2 intravenously on Days 1, 8 and 15 of each 21-day cycle until progressive disease			6	13	13	13