Study Using IMC-A12 (Cixutumumab) With or Without Cetuxim... | NCT00503685

ID	Type	Description
CP02-0657	Other Identifier	ImClone, LLC
CP13-0605	Other Identifier	ImClone, LLC
I5A-IE-JAEL	Other Identifier	Eli Lilly and Company

Label	Type	Description	Intervention Names
IMC-A12	Experimental	Administered every 2 weeks	Biological: IMC-A12
IMC-A12 + cetuximab	Experimental	Administered every 2 weeks	Biological: IMC-A12 Biological: cetuximab
IMC-A12 + cetuximab [Kirsten rat sarcoma (K-ras) wild-type]	Experimental	Participants who have experienced confirmed partial response (PR) or stable disease (SD) ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression are enrolled in this arm.	Biological: IMC-A12 Biological: cetuximab

Name	Type	Description	Arm Group Labels	Other Names
IMC-A12	Biological	10 milligrams/kilogram (mg/kg) intravenous infusion every 2 weeks.	IMC-A12 IMC-A12 + cetuximab IMC-A12 + cetuximab [Kirsten rat sarcoma (K-ras) wild-type]

Measure	Description	Time Frame
Percentage of Participants With Complete Response (CR) or Partial Response [PR, Objective Response Rate (ORR)]	ORR is the percentage of participants with a confirmed CR or PR, as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions. ORR is calculated as a total number of participants with CR or PR from start of the treatment until disease progression or recurrence divided by the total number of participants treated, then multiplied by 100.	Start of randomization/treatment to date of objective progressive disease (PD) up to 28.3 weeks

Measure	Description	Time Frame
Progression-Free Survival (PFS)	PFS was defined as the duration from the date of randomization/treatment to the date of PD or death from any cause. PD was determined using RECIST criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions or the appearance of new lesions. Participants who had no PD or death at the time of the data inclusion cutoff, PFS was censored at their last tumor assessment prior to the cutoff date. Participants who began a new antitumor treatment before evidence of PD were categorized as PD.

Eligibility Module

Eligibility Criteria

Inclusion Criteria

The participant has histologically or cytologically-confirmed colorectal cancer with metastatic disease documented on diagnostic imaging studies
The participant has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded), measuring ≥ 2 centimeter (cm) on conventional measurement techniques or ≥ 1 cm on spiral computed tomography (CT) scan
The participant has clinical documentation of disease progression during treatment or within 6 weeks after receiving the last dose of a therapeutic regimen for metastatic disease containing an anti-EGFR-component (cetuximab or panitumumab). Toxicity or planned treatment break will not be regarded as adequate evidence of disease progression and such participants will not be eligible for this trial
The participant has received at least one prior standard and/or investigational regimen for metastatic disease
The participant is age ≥ 18 years
The participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1 (Karnofsky ≥ 80%
The participant has adequate hematologic function as defined by an absolute neutrophil count ≥ 1500/microliter (μL), hemoglobin ≥ 9 grams/deciliter (g/dL), and a platelet count ≥ 100,000/μL
The participant has adequate hepatic function as defined by a total bilirubin ≤ 1.5 x the upper limit of normal (ULN), and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x the ULN (or ≤ 5 x the ULN in the presence of known liver metastases)
The participant has adequate coagulation function as defined by international normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) ≤ 1.5 x the ULN. Participants on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight heparin, and if on warfarin must have an INR between 2 and 3 and have no active bleeding or pathological condition that carries a high risk of bleeding (for example, tumor involving major vessels or invading the rectal lumen, or known varices)
The participant has adequate renal function as defined by serum creatinine ≤ 1.5 x the institutional ULN or creatinine clearance ≥ 60 milliliters/minute (mL/min) for participants with creatinine levels above the ULN, as well as urine protein ≤ 1+ on urine dipstick or routine urinalysis [(UA), if urine dipstick/routine UA indicates ≥ 2+ protein, a 24-hour urine collection for protein must demonstrate < 1000 milligrams (mg) of protein in 24 hours to allow participation in the study]
The participant has fasting serum glucose < 120 milligrams/deciliter (mg/dL) or below the ULN
The participant has a life expectancy of > 3 months
Because the teratogenicity of IMC-A12 (cixutumumab) is not known, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
The participant has the ability to understand and the willingness to sign a written informed consent document
The participant has a tumor that is K-ras wild-type (absence of mutations at codon 12 or 13, as determined by the DxS K-ras Mutation Kit [polymerase chain reaction (PCR)-based analysis]).
The participant experienced either a confirmed partial response or stable disease of ≥ 24 weeks duration during prior treatment with a cetuximab- or panitumumab-containing regimen except for participants with uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) promoter polymorphism, for example, Gilbert syndrome, confirmed by genotyping or Invader®UGT1A1 Molecular Assay prior to enrollment. Participants enrolled with Gilbert Syndrome must have a total bilirubin ≤ 3 x ULN. If the participant has liver metastases, total bilirubin must be ≤ 3 x ULN.

Exclusion Criteria

The participant has received chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or has not recovered from adverse events due to agents administered more than 4 weeks earlier. Neurotoxicity, if present, must have recovered to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 3.0 grade ≤ 2.
The participant is receiving any other investigational agent(s).
The participant has a history of treatment with other agents targeting the insulin-like growth factor receptor (IGFR).
The participant has known brain or leptomeningeal metastases.
The participant has a history of primary central nervous system tumors, seizures not well controlled with standard medical therapy, or history of stroke within 6 months prior to randomization.
The participant has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab or IMC-A12 (cixutumumab).
The participant has poorly controlled diabetes mellitus. Participants with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within normal range (fasting glucose < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition.
The participant has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, uncontrolled hypertension, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
The participant is pregnant or lactating.
The participant is known to be positive for infection with the human immunodeficiency virus.
The participant is receiving therapy with immune modulators such as cyclosporine or tacrolimus.
The participant has a history of another primary cancer, with the exception of: a) curatively resected nonmelanomatous skin cancer; b) curatively treated cervical carcinoma in-situ; or c) other primary solid tumor curatively resected treated with no known active disease present and no treatment administered for the last 3 years.

Name	Affiliation	Role
E-mail: ClinicalTrials@ ImClone.com	Eli Lilly and Company	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
ImClone Investigational Site		Los Angeles	California	90095	United States
ImClone Investigational Site

ID	Title	Description
FG000	IMC-A12	Participants received 10 milligrams/kilogram (mg/kg) IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
FG001	IMC-A12 + Cetuximab

ID	Title	Description
BG000	IMC-A12	Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
BG001	IMC-A12 + Cetuximab	Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
BG002	IMC-A12 + Cetuximab (K-ras Wild-type)	Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00023 BG00121 BG00220 BG00364

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 Complete Response (CR) or Partial Response [PR, Objective Response Rate (ORR)]

ORR is the percentage of participants with a confirmed CR or PR, as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions. ORR is calculated as a total number of participants with CR or PR from start of the treatment until disease progression or recurrence divided by the total number of participants treated, then multiplied by 100.

All randomized/enrolled participants who received at least 1 dose of study drug.

Posted

Number

95% Confidence Interval

percentage of participants

Start of randomization/treatment to date of objective progressive disease (PD) up to 28.3 weeks

ID	Title	Description
OG000	IMC-A12	Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG001	IMC-A12 + Cetuximab	Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG002	IMC-A12 + Cetuximab (K-ras Wild-type)	Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.

Units	Counts
Participants	OG00023 OG00121 OG00220

Title

Denominators

Categories

Title	Measurements
	OG0000.0(0.0 to 14.8) OG0014.8(0.1 to 23.8) OG0020.0(0.0 to 16.8)

Secondary

Progression-Free Survival (PFS)

PFS was defined as the duration from the date of randomization/treatment to the date of PD or death from any cause. PD was determined using RECIST criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions or the appearance of new lesions. Participants who had no PD or death at the time of the data inclusion cutoff, PFS was censored at their last tumor assessment prior to the cutoff date. Participants who began a new antitumor treatment before evidence of PD were categorized as PD.

All randomized/enrolled participants who received at least 1 dose of study drug. The number of participants censored was 0 for IMC-A12 group, 1 for IMC-A12 + cetuximab group and 1 for IMC-A12 + cetuximab (K-ras wild-type) group.

Posted

Median

95% Confidence Interval

weeks

Randomization/treatment to measured PD up to 28.3 weeks

ID	Title	Description
OG000	IMC-A12	Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG001	IMC-A12 + Cetuximab	Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.

Secondary

Overall Survival (OS)

OS is defined as the duration from the date of randomization/treatment to the date of death from any cause. Participants who were alive at the time of the data inclusion cutoff, OS was censored at the last date the participant was known to be alive.

All randomized/enrolled participants who received at least 1 dose of study drug. The number of participants censored was 5 for IMC-A12 group, 4 for IMC-A12 + cetuximab group and 11 for IMC-A12 + cetuximab (K-ras wild-type) group.

Posted

Median

95% Confidence Interval

months

Randomization/treatment to date of death from any cause up to 26.9 months

ID	Title	Description
OG000	IMC-A12	Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG001	IMC-A12 + Cetuximab	Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG002	IMC-A12 + Cetuximab (K-ras Wild-type)	Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.

Secondary

Duration of Stable Disease (SD)

The duration of SD is measured from the date of randomization/treatment until the date of PD. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. RECIST criteria version 1.0 was used to asses PR and PD. PR is ≥30% decrease in sum of longest diameter of target lesions. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. Participants who had no PD or death at the time of the data inclusion cutoff, duration of SD was censored at their last tumor assessment prior to the cutoff date.

All randomized/enrolled participants who received at least 1 dose of the study drug and achieved SD or better. The number of participants censored was 0 for IMC-A12 group, 0 for IMC-A12 + cetuximab group and 1 for IMC-A12 + cetuximab (K-ras wild-type) group.

Posted

Median

95% Confidence Interval

weeks

Time from randomization/treatment to first date of PD up to 28.3 weeks

ID	Title	Description
OG000	IMC-A12	Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG001	IMC-A12 + Cetuximab	Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.

Secondary

Duration of Overall Response

The duration of overall response (CR or PR) was defined as the time from first objective status assessment of CR or PR to the first time of PD or death due to any cause. CR, PR and PD were determined using RECIST criteria version 1.0. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions; PD is ≥20% increase in sum of longest diameter of target lesions or the appearance of new lesions. For participants with CR or PR who had no PD or death at the time of the data inclusion cutoff, the duration of overall response was censored at their last tumor assessment prior to the cutoff date. Duration of overall response was not analyzed due to low number of participants with CR or PR.

Zero participants analyzed. Duration of Response for CR or PR data was not collected for analysis due to N=0 CR and N=1 PR.

Posted

Time of response to time of measured PD or death up to 161 days

ID	Title	Description
OG000	IMC-A12	Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG001	IMC-A12 + Cetuximab	Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.

Secondary

Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)

Data presented are the number of participants who experienced nonserious adverse events (AEs) during the study including the 30-day follow-up. A summary of serious AEs (SAEs) and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

All randomized/enrolled participants who received at least 1 dose of study drug.

Posted

Count of Participants

Participants

Randomization/treatment up to 26.9 months

ID	Title	Description
OG000	IMC-A12	Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG001	IMC-A12 + Cetuximab	Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG002	IMC-A12 + Cetuximab (K-ras Wild-type)	Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.

Secondary

Number of Participants Reporting Treatment-Emergent Severe Adverse Events

Data presented are the number of participants who experienced serious adverse events (SAEs) or death during the study including the 30-day follow-up. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

All randomized/enrolled participants who received at least 1 dose of study drug.

Posted

Count of Participants

Participants

Randomization/treatment up to 26.9 months

ID	Title	Description
OG000	IMC-A12	Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG001	IMC-A12 + Cetuximab	Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG002	IMC-A12 + Cetuximab (K-ras Wild-type)	Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.

Secondary

Maximum Concentration (Cmax)

Zero participants analyzed. PK data was not collected for analysis due to the low number of participants in PK.

Posted

Week 1 (Initial dose), Week 3 (Dose 2), Week 5 (Dose 3), Week 7 (Dose 4), Week 9 (Dose 5), and Week 11 (Dose 6)

ID	Title	Description
OG000	IMC-A12	Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG001	IMC-A12 + Cetuximab	Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG002	IMC-A12 + Cetuximab (K-ras Wild-type)	Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.

Secondary

Minimum Concentration (Cmin)

Zero participants analyzed. PK data was not collected for analysis due to the low number of participants in PK.

Posted

Week 1 (Initial dose), Week 3 (Dose 2), Week 5 (Dose 3), Week 7 (Dose 4), Week 9 (Dose 5), and Week 11 (Dose 6)

ID	Title	Description
OG000	IMC-A12	Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG001	IMC-A12 + Cetuximab	Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG002	IMC-A12 + Cetuximab (K-ras Wild-type)	Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.

Secondary

Area Under Serum Concentration (AUC)

Zero participants analyzed. PK data was not collected for analysis due to the low number of participants in PK.

Posted

Week 1 (Initial dose), Week 3 (Dose 2), Week 5 (Dose 3), Week 7 (Dose 4), Week 9 (Dose 5), and Week 11 (Dose 6)

ID	Title	Description
OG000	IMC-A12	Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG001	IMC-A12 + Cetuximab	Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG002	IMC-A12 + Cetuximab (K-ras Wild-type)	Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.

Secondary

Percentage of Participants With Complete Response (CR) or Partial Response (PR, Response Rate) in Participants With Kirsten Rat Sarcoma (K-ras) Mutations

The response rate in participants with K-ras mutations was not collected for analysis.

Zero participants analyzed. Response rate data was not collected for analysis due to N=0 CR and N=1 PR.

Posted

Treatment up to 26.9 months

ID	Title	Description
OG000	IMC-A12 + Cetuximab (K-ras Wild-type)	Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.

Units	Counts
Participants	OG000

Secondary

Expression of Type I Insulin-Like Growth Factor Receptors (IGF-IR)

Zero participants analyzed. No data collected for analysis.

Posted

Randomization/treatment up to 26.9 months

ID	Title	Description
OG000	IMC-A12	Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG001	IMC-A12 + Cetuximab	Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG002	IMC-A12 + Cetuximab (K-ras Wild-type)	Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.

Secondary

Expression of IGF Binding Proteins (IGFBP2, IGFBP3)

Zero participants analyzed. No data collected for analysis.

Posted

Randomization/treatment up to 26.9 months

ID	Title	Description
OG000	IMC-A12	Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG001	IMC-A12 + Cetuximab	Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.
OG002	IMC-A12 + Cetuximab (K-ras Wild-type)	Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected21 at risk EG0020 events0 affected20 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected21 at risk EG0021 events1 affected20 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0003 events2 affected23 at risk EG0010 events0 affected21 at risk EG0021 events1 affected20 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected21 at risk EG0020 events0 affected20 at risk
Constipation	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected21 at risk EG0021 events1 affected20 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected21 at risk EG0020 events0 affected20 at risk
Nausea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected21 at risk EG0020 events0 affected20 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected21 at risk EG0021 events1 affected20 at risk
Vomiting	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected21 at risk EG0020 events0 affected20 at risk
Asthenia	General disorders	MedDRA 10.0	Systematic Assessment	EG0002 events2 affected23 at risk EG0010 events0 affected21 at risk EG0020 events0 affected20 at risk
Disease progression	General disorders	MedDRA 10.0	Systematic Assessment	EG0002 events2 affected23 at risk EG0011 events1 affected21 at risk EG0020 events0 affected20 at risk
Fatigue	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected21 at risk EG0021 events1 affected20 at risk
Infusion related reaction	General disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected21 at risk EG0020 events0 affected20 at risk
Pyrexia	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected21 at risk EG0020 events0 affected20 at risk
Bile duct obstruction	Hepatobiliary disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected21 at risk EG0020 events0 affected20 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected21 at risk EG0020 events0 affected20 at risk
Bacteraemia	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected21 at risk EG0020 events0 affected20 at risk
Pneumonia	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected21 at risk EG0020 events0 affected20 at risk
Sepsis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected21 at risk EG0020 events0 affected20 at risk
Urinary tract infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected21 at risk EG0020 events0 affected20 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected21 at risk EG0020 events0 affected20 at risk
Post procedural bile leak	Injury, poisoning and procedural complications	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0013 events1 affected21 at risk EG0020 events0 affected20 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected21 at risk EG0020 events0 affected20 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected21 at risk EG0020 events0 affected20 at risk
Blood bilirubin increased	Investigations	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected21 at risk EG0020 events0 affected20 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0011 events1 affected21 at risk EG0020 events0 affected20 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected21 at risk EG0020 events0 affected20 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected21 at risk EG0021 events1 affected20 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected21 at risk EG0021 events1 affected20 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected21 at risk EG0021 events1 affected20 at risk
Headache	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected21 at risk EG0020 events0 affected20 at risk
Acute prerenal failure	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected21 at risk EG0020 events0 affected20 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected21 at risk EG0020 events0 affected20 at risk
Ureteric obstruction	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected21 at risk EG0020 events0 affected20 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0010 events0 affected21 at risk EG0021 events1 affected20 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected21 at risk EG0021 events1 affected20 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0013 events2 affected21 at risk EG0020 events0 affected20 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0003 events3 affected23 at risk EG0012 events2 affected21 at risk EG0021 events1 affected20 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0002 events2 affected23 at risk EG0012 events2 affected21 at risk EG0021 events1 affected20 at risk
Constipation	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0004 events4 affected23 at risk EG0012 events2 affected21 at risk EG0022 events2 affected20 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0002 events2 affected23 at risk EG0016 events4 affected21 at risk EG0025 events4 affected20 at risk
Nausea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0004 events3 affected23 at risk EG0019 events6 affected21 at risk EG0023 events3 affected20 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0011 events1 affected21 at risk EG0023 events3 affected20 at risk
Vomiting	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0003 events2 affected23 at risk EG0015 events3 affected21 at risk EG0024 events4 affected20 at risk
Fatigue	General disorders	MedDRA 10.0	Systematic Assessment	EG0009 events7 affected23 at risk EG00111 events8 affected21 at risk EG0029 events8 affected20 at risk
Mucosal inflammation	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0012 events2 affected21 at risk EG0020 events0 affected20 at risk
Pyrexia	General disorders	MedDRA 10.0	Systematic Assessment	EG0003 events3 affected23 at risk EG0012 events2 affected21 at risk EG0021 events1 affected20 at risk
Paronychia	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0012 events1 affected21 at risk EG0023 events2 affected20 at risk
Blood bilirubin increased	Investigations	MedDRA 10.0	Systematic Assessment	EG0003 events2 affected23 at risk EG0011 events1 affected21 at risk EG0020 events0 affected20 at risk
Weight decreased	Investigations	MedDRA 10.0	Systematic Assessment	EG0005 events4 affected23 at risk EG0013 events2 affected21 at risk EG0020 events0 affected20 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0003 events3 affected23 at risk EG0015 events3 affected21 at risk EG0027 events5 affected20 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0002 events2 affected23 at risk EG0013 events3 affected21 at risk EG0021 events1 affected20 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0014 events3 affected21 at risk EG0020 events0 affected20 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG00110 events4 affected21 at risk EG0020 events0 affected20 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0004 events3 affected23 at risk EG0013 events2 affected21 at risk EG0021 events1 affected20 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected21 at risk EG0022 events2 affected20 at risk
Dizziness	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0003 events3 affected23 at risk EG0014 events2 affected21 at risk EG0021 events1 affected20 at risk
Dysgeusia	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0002 events2 affected23 at risk EG0012 events2 affected21 at risk EG0022 events2 affected20 at risk
Headache	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0012 events2 affected21 at risk EG0026 events6 affected20 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0012 events2 affected21 at risk EG0021 events1 affected20 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0007 events7 affected23 at risk EG0014 events3 affected21 at risk EG0021 events1 affected20 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0012 events2 affected21 at risk EG0020 events0 affected20 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected23 at risk EG0012 events2 affected21 at risk EG0020 events0 affected20 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG00119 events12 affected21 at risk EG00214 events9 affected20 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0013 events3 affected21 at risk EG0027 events7 affected20 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected21 at risk EG0022 events2 affected20 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0012 events2 affected21 at risk EG0025 events4 affected20 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0014 events3 affected21 at risk EG0021 events1 affected20 at risk
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0011 events1 affected21 at risk EG0027 events6 affected20 at risk
Hypertension	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected23 at risk EG0010 events0 affected21 at risk EG0022 events2 affected20 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
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	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	IMC-A12	Participants received 10 mg/kg IMC-A12 intravenous infusion over 1 hour every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	7	23	18	23
EG001	IMC-A12 + Cetuximab	Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	6	21	19	21
EG002	IMC-A12 + Cetuximab (K-ras Wild-type)	Participants with K-ras wild-type who experienced confirmed PR or SD ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression were enrolled in this arm. Participants received cetuximab 500 mg/m² intravenous infusion over 2 hours followed by 10 mg/kg IMC-A12 intravenous infusion over 1 hour. This sequence was repeated every 2 weeks until there was evidence of PD, unacceptable toxicity, or withdrawal of consent.	4	20	20	20