Cetuximab-IRDye 800CW and Intraoperative Imaging in Finding Pancreatic Cancer in Patients Undergoing Surgery

• Sponsor: Eben Rosenthal (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02736578
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 8
• Location: 1
• Arms: 2
• Duration (Months): 10.7
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This phase 1-2 trial studies the side effects and best dose of cetuximab-IRDye 800CW when used with intraoperative imaging, to determine the utility of cetuximab-IRDye 800CW to identify and assess pancreatic cancer in patients undergoing surgery to remove the tumor. Cetuximab-IRDye 800CW may help doctors better identify cancer in the operating room by making the cancer visible when viewed through a fluorescent imaging system.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Adenocarcinoma	Drug: Cetuximab-IRDye800; Drug: Cetuximab	Phase 2

Detailed Description

This is a dose-escalation study of 50 mg or 100 mg cetuximab-IRDye800.

Clearance of the tumor margin during surgical resection of pancreatic cancer is clinical importance, as margin-positive resections are suspected to be associated with rapid emergence of distant metastases shortly after surgery. However, pancreatic cancer is known to be difficult to visualize intraoperatively. Nonetheless, better detection of tumor tissue might improve the rate of complete tumor clearance, thereby improving outcomes. However, in order to be actionable, the data from such enhanced tumor detection must be available during the resection procedure. This study evaluates the use of a dye, Cetuximab-IRDye 800CW, that is administered pre-surgery, and is detectable during the surgical procedure.

Florescent Imaging Cetuximab is a chimeric (mouse/human) monoclonal antibody that targets the epidermal growth factor (EGF) receptor (EGFR). EGFR is highly-expressed in pancreatic ductal adenocarcinoma (PDAC) and is a good target for antibody-mediated imaging, due to its transmembrane position. Cetuximab-IRDye 800CW is cetuximab labeled with IRDye800, an N-hydroxysuccinimide (NHS) ester infrared dye. IRDye800 has very similar properties compared to indocyanine green, and indocyanine green is readily detectable with a number of imaging systems. This study evaluates the Cetuximab-IRDye 800CW as a intraoperative labeling agent.

Patients receive Cetuximab-IRDye 800CW intravenously (IV) at 50 mg or 100 mg over 30 minutes to 1 hour on day 0. Within 2 to 5 days, patients undergo surgery with intraoperative imaging. Cetuximab-IRDye 800CW is used as part of a tumor-targeted molecular imaging procedure operating on the principles of differential accumulation of the antibody-dye conjugate in pancreatic tumor tissue vs normal pancreatic tissue vs pancreatitis tissue.

Excised tissues are prepared as formalin-fixed paraffin-embedded (FFPE) blocks for assessment of fluorescent intensity.

Photoacoustic imaging (PAI) For purposes of non-quantitative comparison, photoacoustic imaging (PAI) of the tumor lesions is also conducted. PAI refers to a non-invasive evaluation by ultrasound of the area of the resected tumor and surrounding tissue. PAI may have special utility for detecting tumors within 5 to 7 mm of depth, with a high degree of spatial resolution, which might be useful to enhance generation of tumor-free surgical margins. PAI does not utilize ionizing radiation, and should complement and conform to the findings from the fluorescent imaging.

PRIMARY OBJECTIVE:

Determine the efficacy of cetuximab-IRDye800 in intraoperatively identifying pancreatic cancer compared to surrounding normal pancreatic and extrapancreatic tissue, as measured by tumor-to-background ratio.

SECONDARY OBJECTIVE:

Determine the tolerability of the cetuximab IRDye800 as an imaging agent in patients undergoing resection of pancreatic cancer.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Intraoperative Pancreatic Cancer Detection Using Multimodality Molecular Imaging
• Study Start Date: Jul 1, 2016
• Actual Primary Completion Date: Apr 24, 2017
• Actual Study Completion Date: May 22, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cetuximab IRDye800, 50 mg On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 50 mg, followed by surgery with intraoperative imaging within 2 to 5 days.	Drug: Cetuximab-IRDye800; Administered intravenously (IV) at 50 or 100 mg; Other Names: Cetuximab-IRDye 800CW ; Drug: Cetuximab; Administered as a 100 mg IV loading dose; Other Names: Erbitux C225
Experimental: Cetuximab IRDye800, 100 mg On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 100 mg, followed by surgery with intraoperative imaging within 2 to 5 days.	Drug: Cetuximab-IRDye800; Administered intravenously (IV) at 50 or 100 mg; Other Names: Cetuximab-IRDye 800CW ; Drug: Cetuximab; Administered as a 100 mg IV loading dose; Other Names: Erbitux C225

Outcome Measures

Primary Outcome Measures

1. Peri-operative Cetuximab-IRDye800 Fluorescent Imaging, Both Doses [up to 5 days]

   Cetuximab-IRDye800 (50 mg or 100 mg) was administered pre-operatively, and the uptake of the dye was assessed by observed fluorescence intra-operatively (ie, in vivo) and post-operatively (ex vivo, or "back table"), in tumorous (tumor or tumor-bearing lymph nodes) or normal (non-tumorous) tissues. Collectively, intra-operative and immediately post-operative are considered "peri-operative." The outcome tumor-to-background ratio (TBR) is measured as the mean of the ratios observed between tumor and normal tissue for the participants, and the outcome is expressed as the mean with standard deviation.

Secondary Outcome Measures

1. Cetuximab-IRDye800 Labeling Intensity in Tumor and Non-Tumor Tissues (Ex Vivo) [up to 14 days]

   Cetuximab-IRDye800 (50 mg or 100 mg) florescence intensity was assessed in normal pancreatic tissue; pancreatitis tissue; and pancreatic tumor tissue prepared as formalin-fixed paraffin-embedded (FFPE) blocks. Fluorescent intensity was measured in the image for each tissue, and expressed as counts per pixel. The outcome is expressed for each tissue as the dose-independent mean counts/pixel for the cohort. The outcome is expressed as the mean counts/pixel with standard deviation.

2. Effect of Cetuximab-IRDye800 Dose on Fluorescence Intensity [up to 14 days]

   Cetuximab-IRDye800 (50 mg or 100 mg) florescence intensity was assessed in normal pancreatic tissue; pancreatitis tissue; and pancreatic tumor tissue prepared as formalin-fixed paraffin-embedded (FFPE) blocks. Fluorescent intensity was measured in the image for each tissue, and expressed as counts per pixel. The outcome is expressed for each tissue as the dose-independent mean fluorescent intensity (MFI) for the cohort. The outcome is expressed as a mean with standard deviation, by dose.

3. Sensitivity and Specificity of Ex Vivo Fluorescent Imaging [up to 14 days]

   Sensitivity is the ability of a test to correctly identify patients with the condition, ie, how well Cetuximab-IRDye800 fluorescent imaging detects true-positive patients. Sensitivity is defined as [TP/(TP+FN)], where TP=true-positive, and FN=false-negative. The outcome is a % without dispersion. A higher % means a greater probability that an imaging target identified as cancerous is confirmed by histology to be cancerous, and a lower % means reduced confidence in that result. Specificity is the ability of a test to correctly identify patients who do not have the condition, ie, how well Cetuximab-IRDye800 fluorescent imaging detects true-negative patients. Specificity is defined as [TN/(TN+FP)], where TN=true-negative, and FP=false-positive. The outcome is a % without dispersion. A higher % means a greater probability that an imaging target identified as non-cancerous is confirmed by histology to be non-cancerous, and a lower % means reduced confidence in that result.

4. Cetuximab-IRDye800 Tumor Detection in Lymph Nodes [up to 14 days]

   Cetuximab-IRDye800 (50 mg or 100 mg) florescence intensity was assessed in excised lymph nodes (ie, ex vivo) that were histologically-determined to be normal or tumor-bearing. Fluorescent intensity was measured in the image for each lymph using close-field fluorescence imaging and expressed as counts per pixel. The outcome is expressed for each tissue as the dose-independent mean fluorescent intensity (MFI) for the cohort. The outcome is expressed as the mean MFI with standard deviation.

5. Signal-to-Noise Ratio (SNR) by Ex Vivo Photoacoustic Imaging (PAI) [up to 5 days]

   Photoacoustics were assessed as the signal-to-noise ratio (SNR), a unit-less number, as observed for tumor vs surrounding tissue using an ultrasound device. The value observed for tumor tissue is considered signal, and the value for normal tissue is considered noise. The more the ratio is greater than 1 reflects the more that the tumor tissue reflects an ultrasound signal compared to normal tissue. The outcome is expressed as the ratio of mean SNR signal for tumor tissue to normal tissue, without dispersion.

6. Signal-to-Noise Ratio (SNR) by In Vivo Photoacoustic Imaging (PAI) [up to 5 days]

   Photoacoustic imaging (PAI) was to be used to evaluate tumor and normal margin tissues (waste tissue) immediately peri-operatively (in vivo) and prior to pathological evaluation. The signal-to-noise ratio (SNR) as measured in dB of the tumor was to be calculated in the tumor specimens for comparison to surrounding normal tissue. The outcome would be expressed as the mean of the ratios, with standard deviation, and data used to qualitatively confirm the findings with Cetuximab-IRDye 800CW fluorescent imaging.

7. Toxicity (≥ Grade 2) [Up to 30 days]

   Toxicity was assessed as the number of grade 2 or greater adverse events [Common Terminology Criteria for Adverse Events (CTCAE) version 4.03] determined to be clinically-significant and definitely-, probably-, or possibly-related to cetuximab-IRDye 800CW. The outcome is reported as the number of treatment-related adverse events ≥ grade 2 without dispersion, by dose level.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

INCLUSION CRITERIA

• Clinically suspected or biopsy confirmed diagnosis of pancreatic adenocarcinoma

• Planned standard of care surgery with curative intent for pancreatic adenocarcinoma

• ≥ 19 years of age

• Life expectancy of more than 12 weeks

• EITHER

• Karnofsky performance status of at least 70%, OR

• Eastern Cooperative Oncology Group (ECOG)/Zubrod level 1

• Hemoglobin ≥ 9 gm/dL

• Platelet count ≥ 100,000/mm^3

• Magnesium > the lower limit of normal (LLN) per institution normal lab values

• Potassium > LLN

• Calcium > LLN

• Thyroid-stimulating hormone (TSH) < 13 micro International units/mL

EXCLUSION CRITERIA

• Received an investigational drug within 30 days prior to first dose of cetuximab IRDye800

• Myocardial infarction (MI); cerebrovascular accident (CVA); uncontrolled congestive heart failure (CHF); or unstable angina within 6 months prior to enrollment

• History of infusion reactions to cetuximab or other monoclonal antibody therapies

• Pregnant or breastfeeding

• Evidence of QT prolongation on pretreatment electrocardiography (ECG) (greater than 440 ms in males or greater than 450 ms in females)

• Lab values that in the opinion of the primary surgeon would prevent surgical resection

• Patients receiving class IA (quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94304

Sponsors and Collaborators

• Eben Rosenthal
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: George Poultsides, MD, Stanford University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 9, 2016

More Information

Publications

• Rosenthal EL, Kulbersh BD, Duncan RD, Zhang W, Magnuson JS, Carroll WR, Zinn K. In vivo detection of head and neck cancer orthotopic xenografts by immunofluorescence. Laryngoscope. 2006 Sep;116(9):1636-41.
• Rosenthal EL, Kulbersh BD, King T, Chaudhuri TR, Zinn KR. Use of fluorescent labeled anti-epidermal growth factor receptor antibody to image head and neck squamous cell carcinoma xenografts. Mol Cancer Ther. 2007 Apr;6(4):1230-8.

• Responsible Party: Eben Rosenthal, Professor of Otolaryngology, Stanford University
• ClinicalTrials.gov Identifier: NCT02736578
• Other Study ID Numbers: IRB-35789; NCI-2016-00433; PANC0024; P30CA124435
• First Posted: Apr 13, 2016
• Last Update Posted: Jun 25, 2019
• Last Verified: Jun 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Cetuximab

Study Results

Participant Flow

Arm/Group Title	Cetuximab IRDye800, 50 mg	Cetuximab IRDye800, 100 mg
Arm/Group Description	On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 50 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 50 or 100 mg Cetuximab: Administered as a 100 mg IV loading dose	On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 100 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 50 or 100 mg Cetuximab: Administered as a 100 mg IV loading dose
Period Title: Overall Study
STARTED	6	2
COMPLETED	5	2
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Cetuximab IRDye800, 50 mg	Cetuximab IRDye800, 100 mg	Total
Arm/Group Description	On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 50 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 50 or 100 mg Cetuximab: Administered as a 100 mg IV loading dose	On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 100 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 50 or 100 mg Cetuximab: Administered as a 100 mg IV loading dose	Total of all reporting groups
Overall Participants	6	2	8
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	4 66.7%	0 0%	4 50%
>=65 years	2 33.3%	2 100%	4 50%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.5 (7.9)	70.4 (7.1)	65.2 (7.9)
Sex: Female, Male (Count of Participants)
Female	2 33.3%	0 0%	2 25%
Male	4 66.7%	2 100%	6 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 16.7%	0 0%	1 12.5%
Not Hispanic or Latino	5 83.3%	2 100%	7 87.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 16.7%	0 0%	1 12.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	4 66.7%	2 100%	6 75%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 16.7%	0 0%	1 12.5%
Region of Enrollment (participants) [Number]
United States	6 100%	2 100%	8 100%

Outcome Measures

1. Primary Outcome

Title	Peri-operative Cetuximab-IRDye800 Fluorescent Imaging, Both Doses
Description	Cetuximab-IRDye800 (50 mg or 100 mg) was administered pre-operatively, and the uptake of the dye was assessed by observed fluorescence intra-operatively (ie, in vivo) and post-operatively (ex vivo, or "back table"), in tumorous (tumor or tumor-bearing lymph nodes) or normal (non-tumorous) tissues. Collectively, intra-operative and immediately post-operative are considered "peri-operative." The outcome tumor-to-background ratio (TBR) is measured as the mean of the ratios observed between tumor and normal tissue for the participants, and the outcome is expressed as the mean with standard deviation.
Time Frame	up to 5 days

Outcome Measure Data

Analysis Population Description

Due to small numbers and the expression of the outcome value as a mean of ratios, the analysis was conducted on all evaluable participants as a single cohort in order to reduce variance/dispersion.

Arm/Group Title	Cetuximab IRDye800, 50 mg
Arm/Group Description	On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 50 or 100 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 50 or 100 mg Cetuximab: Administered as a 100 mg IV loading dose
Measure Participants	6
In vivo (tumor at resection)	2.3 (0.72)
In vivo (lymph node at resection)	6.3 (0.82)
Ex vivo (post-operative, back-table)	3.4 (0.4)

2. Secondary Outcome

Title	Cetuximab-IRDye800 Labeling Intensity in Tumor and Non-Tumor Tissues (Ex Vivo)
Description	Cetuximab-IRDye800 (50 mg or 100 mg) florescence intensity was assessed in normal pancreatic tissue; pancreatitis tissue; and pancreatic tumor tissue prepared as formalin-fixed paraffin-embedded (FFPE) blocks. Fluorescent intensity was measured in the image for each tissue, and expressed as counts per pixel. The outcome is expressed for each tissue as the dose-independent mean counts/pixel for the cohort. The outcome is expressed as the mean counts/pixel with standard deviation.
Time Frame	up to 14 days

Outcome Measure Data

Analysis Population Description

Due to small numbers and the expression of the outcome value as a mean of ratios, the analysis was conducted on all evaluable participants as a single cohort in order to reduce variance/dispersion.

Arm/Group Title	Cetuximab IRDye800, 50 mg
Arm/Group Description	On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 50 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 50 or 100 mg Cetuximab: Administered as a 100 mg IV loading dose
Measure Participants	6
Normal pancreatic tissue	0.02 (0.01)
Pancreatitis tissue	0.04 (0.02)
Pancreatic tumor tissue	0.09 (0.06)

3. Secondary Outcome

Title	Effect of Cetuximab-IRDye800 Dose on Fluorescence Intensity
Description	Cetuximab-IRDye800 (50 mg or 100 mg) florescence intensity was assessed in normal pancreatic tissue; pancreatitis tissue; and pancreatic tumor tissue prepared as formalin-fixed paraffin-embedded (FFPE) blocks. Fluorescent intensity was measured in the image for each tissue, and expressed as counts per pixel. The outcome is expressed for each tissue as the dose-independent mean fluorescent intensity (MFI) for the cohort. The outcome is expressed as a mean with standard deviation, by dose.
Time Frame	up to 14 days

Outcome Measure Data

Analysis Population Description

Tissue sampling and labeling can be imprecise, and there may not have been residual tissue after standard-of-care pathological analysis. Data were not obtained for all participants.

Arm/Group Title	Cetuximab IRDye800, 50 mg	Cetuximab IRDye800, 100 mg
Arm/Group Description	On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 50 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 50 mg Cetuximab: Administered as a 100 mg IV loading dose	On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 100 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 100 mg Cetuximab: Administered as a 100 mg IV loading dose
Measure Participants	4	2
Normal pancreatic tissue	0.02 (0.01)	0.03 (0.02)
Pancreatitis tissue	0.03 (0.02)	0.06 (0.03)
Pancreatic tumor tissue	0.09 (0.06)	0.10 (0.05)

4. Secondary Outcome

Title	Sensitivity and Specificity of Ex Vivo Fluorescent Imaging
Description	Sensitivity is the ability of a test to correctly identify patients with the condition, ie, how well Cetuximab-IRDye800 fluorescent imaging detects true-positive patients. Sensitivity is defined as [TP/(TP+FN)], where TP=true-positive, and FN=false-negative. The outcome is a % without dispersion. A higher % means a greater probability that an imaging target identified as cancerous is confirmed by histology to be cancerous, and a lower % means reduced confidence in that result. Specificity is the ability of a test to correctly identify patients who do not have the condition, ie, how well Cetuximab-IRDye800 fluorescent imaging detects true-negative patients. Specificity is defined as [TN/(TN+FP)], where TN=true-negative, and FP=false-positive. The outcome is a % without dispersion. A higher % means a greater probability that an imaging target identified as non-cancerous is confirmed by histology to be non-cancerous, and a lower % means reduced confidence in that result.
Time Frame	up to 14 days

Outcome Measure Data

Analysis Population Description

Outcome results for sensitivity and specificity of fluorescent imaging were available by dose, and compiled across both doses. Tissue sampling and labeling can be imprecise, and there may not have been residual tissue after standard-of-care pathological analysis. Data were not obtained for all participants.

Arm/Group Title	Cetuximab IRDye800, 50 mg	Cetuximab IRDye800, 100 mg	Cetuximab IRDye800, Both Doses
Arm/Group Description	On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 50 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 50 mg Cetuximab: Administered as a 100 mg IV loading dose	On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 100 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 100 mg Cetuximab: Administered as a 100 mg IV loading dose	On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 100 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 50 or at 100 mg Cetuximab: Administered as a 100 mg IV loading dose
Measure Participants	4	2	6
Measure Lymph nodes	72	72	144
Sensitivity	100.0	88.2	96.1
Specificity	78.0	32.1	67.0

5. Secondary Outcome

Title	Cetuximab-IRDye800 Tumor Detection in Lymph Nodes
Description	Cetuximab-IRDye800 (50 mg or 100 mg) florescence intensity was assessed in excised lymph nodes (ie, ex vivo) that were histologically-determined to be normal or tumor-bearing. Fluorescent intensity was measured in the image for each lymph using close-field fluorescence imaging and expressed as counts per pixel. The outcome is expressed for each tissue as the dose-independent mean fluorescent intensity (MFI) for the cohort. The outcome is expressed as the mean MFI with standard deviation.
Time Frame	up to 14 days

Outcome Measure Data

Analysis Population Description

The relationship of the number of participants to number of analyzed lymph nodes (tumor-bearing or not) is not 1:1, & tissue sampling & labeling are imprecise. Participants could contribute none or multiple normal and tumor-bearing lymph node for analysis. Data were not obtained for all participants.

Arm/Group Title	Cetuximab IRDye800, 50 mg	Cetuximab IRDye800, 100 mg
Arm/Group Description	On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 50 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 50 mg Cetuximab: Administered as a 100 mg IV loading dose	On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 100 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 100 mg Cetuximab: Administered as a 100 mg IV loading dose
Measure Participants	4	2
Measure Lymph nodes	72	72
Tumor-bearing lymph nodes	0.071 (0.01)	0.046 (0.007)
Histologically normal lymph nodes	0.018 (0.001)	0.035 (0.004)

6. Secondary Outcome

Title	Signal-to-Noise Ratio (SNR) by Ex Vivo Photoacoustic Imaging (PAI)
Description	Photoacoustics were assessed as the signal-to-noise ratio (SNR), a unit-less number, as observed for tumor vs surrounding tissue using an ultrasound device. The value observed for tumor tissue is considered signal, and the value for normal tissue is considered noise. The more the ratio is greater than 1 reflects the more that the tumor tissue reflects an ultrasound signal compared to normal tissue. The outcome is expressed as the ratio of mean SNR signal for tumor tissue to normal tissue, without dispersion.
Time Frame	up to 5 days

Outcome Measure Data

Analysis Population Description

Tissue sampling and labeling can be imprecise. Due to small numbers and the expression of the outcome value as a mean of ratios, the analysis was conducted on all evaluable participants as a single cohort. Data were not obtained for all participants. Dispersion was not and can not be determined for the outcome, a ratio (ratio of means).

Arm/Group Title	Cetuximab IRDye800, 50 mg
Arm/Group Description	On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 50 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 50 or 100 mg Cetuximab: Administered as a 100 mg IV loading dose
Measure Participants	4
Number [ratio]	3.7

7. Secondary Outcome

Title	Signal-to-Noise Ratio (SNR) by In Vivo Photoacoustic Imaging (PAI)
Description	Photoacoustic imaging (PAI) was to be used to evaluate tumor and normal margin tissues (waste tissue) immediately peri-operatively (in vivo) and prior to pathological evaluation. The signal-to-noise ratio (SNR) as measured in dB of the tumor was to be calculated in the tumor specimens for comparison to surrounding normal tissue. The outcome would be expressed as the mean of the ratios, with standard deviation, and data used to qualitatively confirm the findings with Cetuximab-IRDye 800CW fluorescent imaging.
Time Frame	up to 5 days

Outcome Measure Data

Analysis Population Description

The in vivo photoacoustic imaging (PAI) component of this study was not IRB-approved, and this part of the study was not conducted.

Arm/Group Title	Cetuximab IRDye800, 50 mg	Cetuximab IRDye800, 100 mg
Arm/Group Description	On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 50 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 50 mg Cetuximab: Administered as a 100 mg IV loading dose	On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 100 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 100 mg Cetuximab: Administered as a 100 mg IV loading dose
Measure Participants	0	0

8. Secondary Outcome

Title	Toxicity (≥ Grade 2)
Description	Toxicity was assessed as the number of grade 2 or greater adverse events [Common Terminology Criteria for Adverse Events (CTCAE) version 4.03] determined to be clinically-significant and definitely-, probably-, or possibly-related to cetuximab-IRDye 800CW. The outcome is reported as the number of treatment-related adverse events ≥ grade 2 without dispersion, by dose level.
Time Frame	Up to 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cetuximab IRDye800, 50 mg	Cetuximab IRDye800, 100 mg
Arm/Group Description	On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 50 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 50 or 100 mg Cetuximab: Administered as a 100 mg IV loading dose	On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 100 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 50 or 100 mg Cetuximab: Administered as a 100 mg IV loading dose
Measure Participants	6	2
Number [Adverse events]	1	0

Adverse Events

Time Frame	30 days +- one week
Arm/Group Title	Cetuximab IRDye800, 50 mg		Cetuximab IRDye800, 100 mg
Arm/Group Description	On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 50 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 50 or 100 mg Cetuximab: Administered as a 100 mg IV loading dose		On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 100 mg, followed by surgery with intraoperative imaging within 2 to 5 days. Cetuximab-IRDye800: Administered intravenously (IV) at 50 or 100 mg Cetuximab: Administered as a 100 mg IV loading dose
All Cause Mortality
	Cetuximab IRDye800, 50 mg		Cetuximab IRDye800, 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/2 (0%)
Serious Adverse Events
	Cetuximab IRDye800, 50 mg		Cetuximab IRDye800, 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		0/2 (0%)
Gastrointestinal disorders
Pancreatic fistula	1/6 (16.7%)	1	0/2 (0%)	0
Other (Not Including Serious) Adverse Events
	Cetuximab IRDye800, 50 mg		Cetuximab IRDye800, 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		2/2 (100%)
Blood and lymphatic system disorders
Anemia	5/6 (83.3%)	16	2/2 (100%)	3
Leukocytosis	1/6 (16.7%)	2	0/2 (0%)	0
Gastrointestinal disorders
Abdominal pain	2/6 (33.3%)	2	0/2 (0%)	0
Constipation	1/6 (16.7%)	1	0/2 (0%)	0
Ileus	1/6 (16.7%)	1	0/2 (0%)	0
Nausea	1/6 (16.7%)	1	0/2 (0%)	0
General disorders
Fever	1/6 (16.7%)	1	0/2 (0%)	0
Pain	3/6 (50%)	4	0/2 (0%)	0
Immune system disorders
Allergic reaction	1/6 (16.7%)	1	0/2 (0%)	0
Infections and infestations
Urinary tract infection	1/6 (16.7%)	1	0/2 (0%)	0
Investigations
Blood bilirubin increased	3/6 (50%)	4	1/2 (50%)	1
Activated partial thromboplastin time prolonged	1/6 (16.7%)	1	0/2 (0%)	0
Alanine aminotransferase increased	5/6 (83.3%)	10	1/2 (50%)	1
Alkaline phosphatase increased	4/6 (66.7%)	5	1/2 (50%)	1
Aspartate aminotransferase increased	5/6 (83.3%)	12	1/2 (50%)	1
Creatinine increased	1/6 (16.7%)	1	0/2 (0%)	0
Electrocardiogram QT corrected interval prolonged	1/6 (16.7%)	1	0/2 (0%)	0
INR increased	2/6 (33.3%)	2	0/2 (0%)	0
Lymphocyte count decreased	2/6 (33.3%)	4	0/2 (0%)	0
Weight loss	2/6 (33.3%)	3	0/2 (0%)	0
Metabolism and nutrition disorders
Acidosis	2/6 (33.3%)	3	1/2 (50%)	1
Hyperglycemia	2/6 (33.3%)	10	0/2 (0%)	0
Hyperkalemia	1/6 (16.7%)	1	0/2 (0%)	0
Hypermagnesemia	1/6 (16.7%)	1	0/2 (0%)	0
Hypoalbuminemia	5/6 (83.3%)	19	1/2 (50%)	2
Hypocalcemia	5/6 (83.3%)	19	2/2 (100%)	3
Hypokalemia	4/6 (66.7%)	7	1/2 (50%)	1
Hypomagnesemia	2/6 (33.3%)	3	0/2 (0%)	0
Hyponatremia	4/6 (66.7%)	9	1/2 (50%)	1
Hypophosphatemia	4/6 (66.7%)	10	1/2 (50%)	1
Musculoskeletal and connective tissue disorders
Back Pain	0/6 (0%)	0	1/2 (50%)	1
Renal and urinary disorders
Urinary retention	1/6 (16.7%)	1	0/2 (0%)	0
Urinary frequency	0/6 (0%)	0	1/2 (50%)	1
Skin and subcutaneous tissue disorders
Erythema	0/6 (0%)	0	1/2 (50%)	1
Surgical and medical procedures
Surgical and medical procedures - Other, specify	2/6 (33.3%)	3	0/2 (0%)	0
Vascular disorders
Hypertension	4/6 (66.7%)	9	1/2 (50%)	1
Hypotension	1/6 (16.7%)	1	0/2 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.