Trial Outcomes & Findings for Study to Evaluate the Effect of Cetuximab on Corrected QT (QTc) Interval Changes in Patients With Advanced Malignancies From Solid Tumors (NCT NCT00698841)

Last Updated: 2015-12-24

Results Overview

12-Lead continuous digital electrocardiogram (ECG) data were collected at preselected time points at baseline visit and on Days 1, 8, 15, 22, and 29. The QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. The corrected QTc is the QT interval corrected for heart rate. Prolongation of the QTc was identified as clinically meaningful at the investigator's discretion.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

79 participants

Primary outcome timeframe

Baseline, Day 1, and then weekly to end of Cycle 1 (28 days)

Results posted on

2015-12-24

Participant Flow

Of 79 participants enrolled, 51 received treatment.

Participant milestones

Participant milestones
Measure	Cetuximab Cetuximab given by intravenous (IV) infusion at an initial dose of 400 mg/m\^2 over 120 minutes on Day 1 followed by a weekly maintenance IV dose of 250 mg/m\^2 over 60 minutes.
Overall Study STARTED	51
Overall Study COMPLETED	33
Overall Study NOT COMPLETED	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Cetuximab Cetuximab given by intravenous (IV) infusion at an initial dose of 400 mg/m\^2 over 120 minutes on Day 1 followed by a weekly maintenance IV dose of 250 mg/m\^2 over 60 minutes.
Overall Study Withdrawal by Subject	2
Overall Study Adverse Event	3
Overall Study Disease progression	7
Overall Study Failure to meet eligibility criteria	2
Overall Study Study drug toxicity	2
Overall Study Other	2

Baseline Characteristics

Study to Evaluate the Effect of Cetuximab on Corrected QT (QTc) Interval Changes in Patients With Advanced Malignancies From Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cetuximab n=51 Participants Cetuximab given by intravenous (IV) infusion at an initial dose of 400 mg/m\^2 over 120 minutes on Day 1 followed by a weekly maintenance IV dose of 250 mg/m\^2 over 60 minutes.
Age, Continuous	61 years STANDARD_DEVIATION 12 • n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	45 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Day 1, and then weekly to end of Cycle 1 (28 days)

Population: Those who met all study criteria and did not require interrupted cetuximab infusion on Day (D)1 or 22; miss an ECG timepoint at baseline, D1, or D22; stop/modify dose of a scheduled drug that prolongs QT/QTc interval, receive other cancer therapy, begin a prohibited drug, or require cetuximab dose reduction before D29; withdraw consent before D23.

Outcome measures

Outcome measures
Measure	Cetuximab n=37 Participants Cetuximab given by intravenous (IV) infusion at an initial dose of 400 mg/m\^2 over 120 minutes on Day 1 followed by a weekly maintenance IV dose of 250 mg/m\^2 over 60 minutes.
Number of Participants With Clinically Meaningful Prolongation of the QT Interval Corrected for Heart Rate (QTc) From Time-matched Baseline	0 Participants

PRIMARY outcome

Timeframe: Predose Day 1 (Baseline) to end of Cycle 1 (28 days)

The QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. The QTc is the QT interval corrected for heart rate. The QTcF=QT/RR\^1/3, where RR=RR interval in seconds. Baseline=predose. Mean change in QTc interval from baseline to time t=QTc interval at time t minus QTc interval at baseline.

Outcome measures

Outcome measures
Measure	Cetuximab n=37 Participants Cetuximab given by intravenous (IV) infusion at an initial dose of 400 mg/m\^2 over 120 minutes on Day 1 followed by a weekly maintenance IV dose of 250 mg/m\^2 over 60 minutes.
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 1 (N=36) Predose	3.8 msec Standard Error 2.5
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 1 (N=37) 1 hour	1.8 msec Standard Error 1.9
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 1 (N=37) 2 hour	0.7 msec Standard Error 2.1
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 1 (N=36) 3 hour	1.2 msec Standard Error 1.6
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 1 (N=37) 6 hour	-2.4 msec Standard Error 1.8
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 8 (N=37) Predose	1.3 msec Standard Error 2.2
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 8 (N=37) 1 hour	1.9 msec Standard Error 2.5
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 8 (N=37) 2 hour	4.5 msec Standard Error 2.7
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 8 (N=36) 3 hour	0.8 msec Standard Error 2.5
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 15 (N=37) Predose	3.2 msec Standard Error 2.7
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 15 (N=37) 1 hour	2.6 msec Standard Error 3.1
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 15 (N=37) 2 hour	1.2 msec Standard Error 3.2
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 15 (N=36) 3 hour	-0.7 msec Standard Error 3.6
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 22 (N=37) Predose	2.3 msec Standard Error 3.3
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 22 (N=37) 1 hour	3.4 msec Standard Error 2.9
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 22 (N=37) 2 hour	4.1 msec Standard Error 3.2
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 22 (N=36) 3 hour	2.2 msec Standard Error 2.8
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 22 (N=37) 6 hour	2.6 msec Standard Error 2.4
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 29 (N=30) Predose	0.0 msec Standard Error 3.4
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 29 (N=30) 1 hour	3.5 msec Standard Error 2.9
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 29 (N=30) 2 hour	3.5 msec Standard Error 2.7
Mean Change in QTc From Time-matched Baseline Assessed Using Fridericia's Correction Formula (QTcF) by Study Day and Time Point Day 29 (N=29) 3 hour	4.0 msec Standard Error 3.0

SECONDARY outcome

Timeframe: Baseline, Day 1, and then weekly to end of Cycle 1 (28 days)

12-Lead continuous digital ECG data were collected at preselected time points at baseline visit and on Days 1, 8, 15, 22, and 29. The PR interval is the time from the onset of the P wave to the beginning of the QRS complex. The QRS interval=deflections in the ECG, comprising Q, R, and S waves, that represent depolarization of the ventricles. Clinically significant was determined at the investigator's discretion.

Outcome measures

Outcome measures
Measure	Cetuximab n=37 Participants Cetuximab given by intravenous (IV) infusion at an initial dose of 400 mg/m\^2 over 120 minutes on Day 1 followed by a weekly maintenance IV dose of 250 mg/m\^2 over 60 minutes.
Number of Participants With Clinically Significant Changes in PR Interval, QRS Interval, and Heart Rate Changes in PR interval	0 Participants
Number of Participants With Clinically Significant Changes in PR Interval, QRS Interval, and Heart Rate Changes in QRS interval	0 Participants
Number of Participants With Clinically Significant Changes in PR Interval, QRS Interval, and Heart Rate Changes in heart rate	0 Participants

SECONDARY outcome

Timeframe: Baseline through Cycle 1 (28 days), continuously

Population: All participants who received at least 1 dose of cetuximab.

AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with treatment. SAE=any untoward medical occurrence that at any dose results in death, is life-threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, or is an important medical event. Treatment related=possibly, probably, or certainly related to or of unknown relationship to study treatment.

Outcome measures

Outcome measures
Measure	Cetuximab n=51 Participants Cetuximab given by intravenous (IV) infusion at an initial dose of 400 mg/m\^2 over 120 minutes on Day 1 followed by a weekly maintenance IV dose of 250 mg/m\^2 over 60 minutes.
Number of Participants With Death, Treatment-related Death, Serious Adverse Events (SAEs), Treatment-related SAEs, Adverse Events (AEs) Leading to Discontinuation, and Treatment-related AEs Leading to Discontinuation Deaths	6 Participants
Number of Participants With Death, Treatment-related Death, Serious Adverse Events (SAEs), Treatment-related SAEs, Adverse Events (AEs) Leading to Discontinuation, and Treatment-related AEs Leading to Discontinuation Treatment-related deaths	0 Participants
Number of Participants With Death, Treatment-related Death, Serious Adverse Events (SAEs), Treatment-related SAEs, Adverse Events (AEs) Leading to Discontinuation, and Treatment-related AEs Leading to Discontinuation SAEs	16 Participants
Number of Participants With Death, Treatment-related Death, Serious Adverse Events (SAEs), Treatment-related SAEs, Adverse Events (AEs) Leading to Discontinuation, and Treatment-related AEs Leading to Discontinuation Treatment-related SAEs	2 Participants
Number of Participants With Death, Treatment-related Death, Serious Adverse Events (SAEs), Treatment-related SAEs, Adverse Events (AEs) Leading to Discontinuation, and Treatment-related AEs Leading to Discontinuation AEs leading to discontinuation	10 Participants
Number of Participants With Death, Treatment-related Death, Serious Adverse Events (SAEs), Treatment-related SAEs, Adverse Events (AEs) Leading to Discontinuation, and Treatment-related AEs Leading to Discontinuation Treatment-related AEs leading to discontinuation	3 Participants

SECONDARY outcome

Timeframe: Baseline through Cycle 1 (28 days), continuously

AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with treatment. AEs of special interest have been sponsor-selected based on the known clinical effects of cetuximab. Treatment related=possibly, probably, or certainly related to or of unknown relationship to study treatment. CTC Grade 1: Mild. Grade 2: Moderate. Grade 3: Severe or medically significant but not immediately life-threatening. Grade 4: Life-threatening.

Outcome measures

Outcome measures
Measure	Cetuximab n=51 Participants Cetuximab given by intravenous (IV) infusion at an initial dose of 400 mg/m\^2 over 120 minutes on Day 1 followed by a weekly maintenance IV dose of 250 mg/m\^2 over 60 minutes.
Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade Infusion reaction (Any grade)	6 Participants
Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade Infusion reaction (Grade 3)	2 Participants
Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade Infusion reaction (Grade 4 or 5)	0 Participants
Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade Acneform rash (Any grade)	32 Participants
Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade Acneform rash (Grade 3)	1 Participants
Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade Acneform rash (Grade 4 or 5)	0 Participants
Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade Cardiac event (Any grade)	2 Participants
Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade Cardiac event (Grade 3)	1 Participants
Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade Cardiac event (Grade 4 or 5)	0 Participants
Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade Treatment-related infusion reaction (Any grade)	6 Participants
Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade Treatment-related infusion reaction (Grade 3)	2 Participants
Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade Treatment-related infusion reaction (Grade 4 or 5)	0 Participants
Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade Treatment-related acneform rash (Any grade)	31 Participants
Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade Treatment-related acneform rash (Grade 3)	1 Participants
Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade Treatment-related acneform rash (Grade 4 or 5)	0 Participants
Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade Treatment-related cardiac event (Any grade)	0 Participants
Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade Treatment-related cardiac event (Grade 3)	0 Participants
Number of Participants With AEs of Special Interest by Worst Common Terminology Criteria (CTC) Grade Treatment-related cardiac event (Grade 4 or 5)	0 Participants

SECONDARY outcome

Timeframe: At screening, at the end of Cycle 1 (28 days)

Population: All participants who received at least 1 dose of cetuximab

BL=baseline; OS=on-study; ULN=upper level of normal. Albumin,low (g/dL) Grade 1:\<LLN-30, Grade 2:\<30-20, Grades 3\&4:\<20. Aspartate aminotransferase (AST)(U/L) Grade 1:\>ULN-2.5\*ULN, Grade 2:\>2.5-5.0\*ULN, Grade 3:\>5.0-20.0\*ULN, Grade 4:\>20.0\*ULN. Total bilirubin, high Grade 1:ULN-1.5\*ULN, Grade 2:\>1.5-3.0\*ULN, Grade 3:\>3.0-10.0\*ULN, Grade 4:\>10.0\*ULN. Alkaline phosphatase (ALP) (U/L) Grade 1:\>ULN-2.5\*ULN, Grade 2:\>2.5-5.0\*ULN, Grade 3:\>5.0-20.0\*ULN, Grade 4:\>20.0\*ULN. Creatinine (mg/dL) Grade 1:\>ULN-1.5\*ULN, Grade 2:\>1.5-3.0\*ULN, Grade 3:\>3.0-6.0\*ULN, Grade 4:\>6.0\*ULN.

Outcome measures

Outcome measures
Measure	Cetuximab n=51 Participants Cetuximab given by intravenous (IV) infusion at an initial dose of 400 mg/m\^2 over 120 minutes on Day 1 followed by a weekly maintenance IV dose of 250 mg/m\^2 over 60 minutes.
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study Albumin, low (BL, Grades 1-4) ( N=48)	18 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study Albumin, low (OS, Grade 1-4) ( N=45)	27 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study Albumin, low (BL, Grades 3 or 4) ( N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study Albumin, low (OS, Grades 3 or 4) ( N=45)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study Albumin, low (BL, Grade 4) (N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study Albumin, low (OS, Grade 4) (N=45)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study AST, high (BL, Grades 1-4) ( N=48)	9 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study AST, high (OS, Grades 1- 4) ( N=45)	19 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study AST, high (BL, Grades 3 or 4) ( N=48)	1 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study AST, high (OS, Grades 3 or 4) ( N=45)	2 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study AST, high (BL, Grade 4) ( N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study AST, high (OS, Grade 4) ( N=45)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study Total bilirubin, high (BL, Grades 1-4) ( N=48)	2 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study Total bilirubin, high (OS, Grades 1-4) ( N=45)	4 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study Total bilirubin, high (BL, Grades 3 or 4) ( N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study Total bilirubin, high (OS, Grades 3 or 4) (N=45)	1 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study Total bilirubin, high (BL, Grade 4) ( N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study Total bilirubin, high (OS, Grade 4) ( N=45)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study ALP, high (BL, Grade 1-4) ( N=48)	18 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study ALP, high (OS, Grade 1-4) ( N=45)	25 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study ALP, high (BL, Grade 3 or 4) ( N=48)	1 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study ALP, high (OS, Grade 3 or 4) ( N=45)	2 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study ALP, high (BL, Grade 4) ( N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study ALP, high (OS, Grade 4) ( N=45)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study Creatinine, high (BL, Grades 1-4) ( N=48)	1 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study Creatinine, high (OS, Grade 1-4) ( N=45)	2 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study Creatinine, high (BL, Grades 3 or 4) ( N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study Creatinine, high (OS, Grades 3 or 4) ( N=45)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study Creatinine, high (BL, Grade 4) ( N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study Creatinine, high (OS, Grade 4) ( N=45)	0 Participants

SECONDARY outcome

Timeframe: At screening, at the end of Cycle 1 (28 days)

Population: All participants who received at least 1 dose of cetuximab

BL=baseline; OS=on-study; LLN=lower level of normal; ULN=upper level of normal. Sodium, low(mmol/L) Grades 1\&2:\<LLN-130, Grade 3:\<130-120, Grade 4:\<120. Sodium, high (mmol/L) Grade 1:\>ULN-150, Grade 2:\>150-155, Grade 3:\>155-160, Grade 4:\>160. Potassium, high (mmol/L) Grade 1:\>ULN-5.5, Grade 2:\>5.5-6.0, Grade 3:\>6.0-7.0, Grade 4:\>7.0. Glucose, low(mg/dL) Grade 1:\<LLN-55, Grade 2:\<55-40, Grade 3:\<40-30, Grade 4:\<30. Glucose, high (mg/dL) Grade 1:\>ULN-160, Grade 2:\>160-250, Grade 3:\>250-500, Grade 4:\>500. Calcium, high(mg/dL) Grade 1:\>ULN-11.5, Grade 2:\>11.5-12.5, Grade 3:\>12.5-13.5, Grade 4:\>13.

Outcome measures

Outcome measures
Measure	Cetuximab n=51 Participants Cetuximab given by intravenous (IV) infusion at an initial dose of 400 mg/m\^2 over 120 minutes on Day 1 followed by a weekly maintenance IV dose of 250 mg/m\^2 over 60 minutes.
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Sodium, low (BL, Grades 1-4) ( N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Sodium, low (OS, Grades 1- 4) ( N=45)	7 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Sodium, low (BL, Grades 3 or 4) ( N=48)	15 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Sodium, low (OS, Grades 3 or 4) ( N=45)	2 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Sodium, low (BL, Grade 4) ( N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Sodium, low (OS, Grade 4) ( N=45)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Sodium, high (BL, Grade 1-4) ( N=48)	1 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Sodium, high (OS, Grades 1-4) ( N=45)	5 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Sodium, high (BL, Grades 3 or 4) ( N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Sodium, high (OS, Grades 3 or 4) ( N=45)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Sodium, high (BL, Grade 4) ( N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Sodium, high (OS, Grade 4) ( N=45)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Potassium, high (BL, Grades 1-4) ( N=48)	2 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Potassium, high (OS, Grades 1-4) ( N=45)	3 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Potassium, high (BL, Grade 3 or 4) ( N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Potassium, high (OS, Grade 3 or 4) ( N=45)	1 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Potassium, high (BL, Grade 4) ( N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Potassium, high (OS, Grade 4) ( N=45)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Glucose, low (BL, Grades 1- 4) ( N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Glucose, low (OS, Grades 1-4) ( N=45)	2 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Glucose, low (BL, Grades 3 or 4) ( N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Glucose, low (OS, Grades 3 or 4) ( N=45)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Glucose, low (BL, Grade 4) ( N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Glucose, low (OS, Grade 4) ( N=45)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Glucose, high (BL, Grades 1- 4) ( N=48)	29 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Glucose, high (OS, Grades 1- 4) ( N=45)	37 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Glucose, high (BL, Grades 3 or 4) (N=48)	2 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Glucose, high (OS, Grades 3 or 4) (N=45)	4 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Glucose, high (BL, Grade 4) (N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Glucose, high (OS, Grade 4) (N=45)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Calcium, low (BL, Grade 1-4) (N=48)	4 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Calcium, low (OS, Grade 1-4) (N=45)	14 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Calcium, low (BL, Grade 3 or 4) (N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Calcium, low (OS, Grades 3 or 4) (N=45)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Calcium, low (BL, Grade 4) (N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Calcium, low (OS, Grade 4) (N=45)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Calcium, high (BL, Grades 1-4) (N=48)	2 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Calcium, high (OS, Grades 1-4) (N=45)	2 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Calcium, high (BL, Grades 3 or 4) (N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Calcium, high (OS, Grades 3 or 4) (N=45)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Calcium, high (BL, Grade 4) (N=48)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Calcium, high (OS, Grade 4) (N=45)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Magnesium, low (BL, Grades 1-4) (N=41)	3 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Magnesium, low (OS, Grades 1-4) (N=38)	11 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Magnesium, low (BL, Grades 3 or 4) (N=41)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Magnesium, low (OS, Grades 3 or 4) (N=38)	1 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Magnesium, low (BL, Grade 4) (N=41)	0 Participants
Number of Participants With Serum Chemistry Abnormalities by Worst CTC Grade at Baseline and On-study (Continued) Magnesium, low (OS, Grade 4) (N=38)	1 Participants

SECONDARY outcome

Timeframe: At screening, weekly prior to start of cetuximab infusion, at end of Cycle 1 (28 days), and at 30-day follow-up

Population: All participants who received at least 1 dose of cetuximab.

BL=baseline; OS=on-study; LLN=lower level of normal. Laboratory values assessed using CTC for AEs, Version 3.0. Hemoglobin (g/dL) Grade 1:\<LLN to 10.0, Grade 2:\<10.0 to 8.0, Grade 3:\<8.0 to 6.5, Grade 4:\<6.5. Platelets Grade 1:LLN to 75.0\*10\^9/L, Grade 2:\<75.0 to 50.0\*10\^9/L, Grade 3:\<50.0 to 25.0\*10\^9/L, Grade 4:\<25.0 to 10\^9/L. White blood cells Grade 1:\<LLN to 3.0\*10\^9/L, Grade 2:\<3.0 to 2.0\*10\^9/L, Grade 3:\<2.0 to 1.0\*10\^9/L, Grade 4:\<1.0\*10\^9/L. Neutrophils Grade 1:\<LLN to 1.5\*10\^9/L, Grade 2:\<1.5 to 1.0\*10\^9/L, Grade 3:\<1.0 to 0.5\*10\^9/L, Grade 4:\<0.5\*10\^9/L.

Outcome measures

Outcome measures
Measure	Cetuximab n=51 Participants Cetuximab given by intravenous (IV) infusion at an initial dose of 400 mg/m\^2 over 120 minutes on Day 1 followed by a weekly maintenance IV dose of 250 mg/m\^2 over 60 minutes.
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study Hemoglobin, low (BL, Grades 1-4) (N=51)	35 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study Hemoglobin, low (OS, Grades 1-4) (N=45)	34 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study Hemoglobin, low (BL, Grades 3 or 4) (N=51)	1 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study Hemoglobin, low (OS, Grades 3 or 4) (N=45)	2 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study Hemoglobin, low (BL, Grade 4) (N=51)	0 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study Hemoglobin, low (OS, Grade 4) (N=45)	0 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study Platelets, low (BL, Grades 1-4) (N=51)	8 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study Platelets, low (OS, Grades 1-4) (N=45)	9 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study Platelets, low (BL, Grades 3 or 4) (N=51)	0 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study Platelets, low (OS, Grades 3 or 4) (N=45)	0 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study Platelets, low (BL, Grade 4) (N=51)	0 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study Platelets, low (OS, Grade 4) (N=45)	0 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study White blood cells, low (BL, Grades 1-4) (N=51)	4 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study White blood cells, low (OS, Grades 1-4) (N=45)	13 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study White blood cells, low (BL, Grades 3 or 4) (N=51)	0 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study White blood cells, low (OS, Grades 3 or 4) (N=45)	0 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study White blood cells, low (BL, Grade 4) (N=51)	0 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study White blood cells, low (OS, Grade 4) (N=45)	0 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study Neutrophils, low (BL, Grades 1-4) (N=47)	0 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study Neutrophils, low (OS, Grades 1-4) (N=44)	5 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study Neutrophils, low (BL, Grade 3 or 4) (N=47)	0 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study Neutrophils, low (OS, Grade 3 or 4) (N=44)	1 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study Neutrophils, low (BL, Grade 4) (N=47)	0 Participants
Number of Participants With Hematology Abnormalities by Worst CTC Grade at Baseline and On-study Neutrophils, low (OS, Grade 4) (N=44)	0 Participants

Adverse Events

Cetuximab

Serious events: 16 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cetuximab n=51 participants at risk Cetuximab given by intravenous (IV) infusion at an initial dose of 400 mg/m\^2 over 120 minutes on Day 1 followed by a weekly maintenance IV dose of 250 mg/m\^2 over 60 minutes.
Cardiac disorders ACUTE CORONARY SYNDROME	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Nervous system disorders HEADACHE	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Gastrointestinal disorders ASCITES	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Gastrointestinal disorders DISTAL INTESTINAL OBSTRUCTION SYNDROME	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Infections and infestations SEPSIS	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Renal and urinary disorders HYDRONEPHROSIS	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Injury, poisoning and procedural complications INCISIONAL HERNIA	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Injury, poisoning and procedural complications JOINT DISLOCATION	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Musculoskeletal and connective tissue disorders NECK PAIN	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Respiratory, thoracic and mediastinal disorders HYPOXIA	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Respiratory, thoracic and mediastinal disorders DYSPNOEA	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Respiratory, thoracic and mediastinal disorders BRONCHOSPASM	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Respiratory, thoracic and mediastinal disorders LUNG INFILTRATION	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Respiratory, thoracic and mediastinal disorders CHRONIC OBSTRUCTIVE PULMONARY DISEASE	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
General disorders PAIN	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
General disorders DISEASE PROGRESSION	7.8% 4/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
General disorders INFUSION RELATED REACTION	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) PANCREATIC CARCINOMA	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) NASOPHARYNGEAL CANCER	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) METASTASES TO CENTRAL NERVOUS SYSTEM	2.0% 1/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)

Other adverse events

Other adverse events
Measure	Cetuximab n=51 participants at risk Cetuximab given by intravenous (IV) infusion at an initial dose of 400 mg/m\^2 over 120 minutes on Day 1 followed by a weekly maintenance IV dose of 250 mg/m\^2 over 60 minutes.
Skin and subcutaneous tissue disorders DERMATITIS ACNEIFORM	17.6% 9/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
General disorders CHILLS	5.9% 3/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
General disorders FATIGUE	9.8% 5/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
General disorders PYREXIA	7.8% 4/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Investigations WEIGHT DECREASED	5.9% 3/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Nervous system disorders HEADACHE	21.6% 11/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Gastrointestinal disorders NAUSEA	11.8% 6/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Gastrointestinal disorders VOMITING	7.8% 4/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Gastrointestinal disorders DIARRHOEA	7.8% 4/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Gastrointestinal disorders ABDOMINAL PAIN	7.8% 4/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Infections and infestations URINARY TRACT INFECTION	7.8% 4/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Blood and lymphatic system disorders ANAEMIA	5.9% 3/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Skin and subcutaneous tissue disorders RASH	43.1% 22/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Skin and subcutaneous tissue disorders PRURITUS	5.9% 3/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)
Skin and subcutaneous tissue disorders SKIN EXFOLIATION	5.9% 3/51 • Baseline through Cycle 1 (28 days) and up to 30 following last dose of study medication (totaling up to 58 days)

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER