Cetuximab-IRDye 800CW in Detecting Tumors in Patients With Malignant Glioma Undergoing Surgery

• Sponsor: Eben Rosenthal (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02855086
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 3
• Location: 1
• Arms: 2
• Actual Duration (Months): 1.7
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

This study is a phase 1-2 trial that evaluates the best dose of cetuximab-IRDye 800CW and how well it works in detecting tumors in patients with malignant glioma who are undergoing surgery. Cetuximab-IRDye 800CW is an optical imaging agent that may help detect tumor cells when a special camera is used.

Condition or Disease	Intervention/Treatment	Phase
Brain Neoplasm; Malignant Glioma	Biological: Cetuximab; Drug: Cetuximab-IRDye 800CW; Procedure: Tumor resection	Phase 1/Phase 2

Detailed Description

This is a dose-escalation study of cetuximab-IRDye 800CW. Patients are assigned to 1 of 2 cohorts.

COHORT I: Patients receive cetuximab intravenously (IV) over 30 minutes and a lower dose of cetuximab IRDye800 IV over 30 minutes to 1 hour on day 0.

COHORT II: Patients receive cetuximab IV over 30 minutes and a higher dose of cetuximab IRDye800 IV over 30 minutes to 1 hour on day 0.

All patients undergo standard of care surgical resection of tumor on days 2-5.

After completion of study, patients are followed up at days 10 and 30.

PRIMARY OBJECTIVE:

Determine the efficacy of cetuximab-IRDye 800CW (cetuximab IRDye800) in intraoperatively identifying malignant glioma compared to surrounding normal central nervous system tissue, as measured by tumor-to-background ratio.

SECONDARY OBJECTIVE:

Determine the tolerability of the cetuximab IRDye800 as an imaging agent in subjects undergoing resection of malignant glioma.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Open-Label Study Evaluating Cetuximab-IRDye800 as an Optical Imaging Agent to Detect Neoplasms During Neurosurgical Procedures
• Actual Study Start Date: Oct 1, 2016
• Actual Primary Completion Date: Nov 8, 2016
• Actual Study Completion Date: Nov 22, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 50 mg cetuximab-IRDye 800 Patients receive cetuximab IV over 30 minutes and a lower dose of cetuximab IRDye800 IV over 30 minutes to 1 hour on day 0. All patients undergo standard of care surgical resection of tumor on days 2 to 5.	Biological: Cetuximab; Administered intravenously (IV); Other Names: Erbitux Chimeric Anti-epidermal growth factor receptor (EGFR0 monoclonal antibody Chimeric Monoclonal Antibody (MoAb) C225 IMC-C225 ; Drug: Cetuximab-IRDye 800CW; Administered intravenously (IV); Other Names: Cetuximab-IRDye 800 Cetuximab-IRDye800 Cetuximab-IRDye800CW ; Procedure: Tumor resection; Standard of care treatment; Other Names: Conventional Surgery
Experimental: 100 mg cetuximab-IRDye 800 Patients receive cetuximab IV over 30 minutes and a higher dose of cetuximab IRDye800 IV over 30 minutes to 1 hour on day 0. All patients undergo standard of care surgical resection of tumor on days 2 to 5.	Biological: Cetuximab; Administered intravenously (IV); Other Names: Erbitux Chimeric Anti-epidermal growth factor receptor (EGFR0 monoclonal antibody Chimeric Monoclonal Antibody (MoAb) C225 IMC-C225 ; Drug: Cetuximab-IRDye 800CW; Administered intravenously (IV); Other Names: Cetuximab-IRDye 800 Cetuximab-IRDye800 Cetuximab-IRDye800CW ; Procedure: Tumor resection; Standard of care treatment; Other Names: Conventional Surgery

Outcome Measures

Primary Outcome Measures

1. Tumor to Background Ratio (TBR) [1 day]

   Tumor to background ratios (TBR) will be generated from still images by comparing the relative fluorescence of normal and tumor tissue. The average fluorescence will be compared to the average fluorescence of the surrounding tissue using the paired student's T test for each specimen.

Secondary Outcome Measures

1. Incidence of Adverse Events [Up to 30 days]

   The incidence of serious and non-serious adverse events is reported as the number of adverse events (Grade 2 or higher), as graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Data are reported by number of events by treatment level.

Eligibility Criteria

Criteria

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

INCLUSION CRITERIA

• Suspected brain tumors to undergo removal (surgical resection) as standard of care, as assessed by the operating surgeon

• Life expectancy of > 12 weeks

• Karnofsky performance status of at least 70% or Eastern Cooperative Oncology Group (ECOG)/Zubrod level 1

• Hemoglobin ≥ 9 gm/dL

• Platelet count ≥ 100,000/mm³

• Magnesium, potassium and calcium > the lower limit of normal per institution normal lab values

• 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

• Within 6 months prior to enrollment, myocardial infarction (MI); cerebrovascular accident (CVA); uncontrolled congestive heart failure (CHF); significant liver disease; or unstable angina

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

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

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

• Pregnant or breastfeeding

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Eben Rosenthal
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Gordon Li, MD, Stanford University
• Principal Investigator: Eben Rosenthal, MD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eben Rosenthal, Professor of Otolaryngology, Stanford University
• ClinicalTrials.gov Identifier: NCT02855086
• Other Study ID Numbers: IRB-37595; NCI-2016-01165; BRNCNS0008; P30CA124435; IRB-37595
• First Posted: Aug 4, 2016
• Last Update Posted: Mar 31, 2020
• Last Verified: Mar 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neoplasms; Glioma; Brain Neoplasms; Antineoplastic Agents, Immunological; Cetuximab; Antibodies; Immunoglobulins; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Cohort 1 (Cetuximab, Lower Dose Cetuximab-IRDye 800, Surgery)	Cohort 2 (Cetuximab, Higher Dose Cetuximab-IRDye 800, Surgery)
Arm/Group Description	Patients receive cetuximab IV over 30 minutes and a lower dose of cetuximab IRDye800 IV over 30 minutes to 1 hour on day 0. All patients undergo standard of care surgical resection of tumor on days 2 to 5. Cetuximab: Given IV Cetuximab-IRDye 800CW: Given IV Conventional Surgery: Undergo tumor resection Laboratory Biomarker Analysis: Correlative studies	Patients receive cetuximab IV over 30 minutes and a higher dose of cetuximab IRDye800 IV over 30 minutes to 1 hour on day 0. All patients undergo standard of care surgical resection of tumor on days 2 to 5. Cetuximab: Given IV Cetuximab-IRDye 800CW: Given IV Conventional Surgery: Undergo tumor resection Laboratory Biomarker Analysis: Correlative studies
Period Title: Overall Study
STARTED	2	1
COMPLETED	2	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Cohort 1 (Cetuximab, Lower Dose Cetuximab-IRDye 800, Surgery)	Cohort 2 (Cetuximab, Higher Dose Cetuximab-IRDye 800, Surgery)	Total
Arm/Group Description	Patients receive cetuximab IV over 30 minutes and a lower dose of cetuximab IRDye800 IV over 30 minutes to 1 hour on day 0. All patients undergo standard of care surgical resection of tumor on days 2 to 5. Cetuximab: Given IV Cetuximab-IRDye 800CW: Given IV Conventional Surgery: Undergo tumor resection Laboratory Biomarker Analysis: Correlative studies	Patients receive cetuximab IV over 30 minutes and a higher dose of cetuximab IRDye800 IV over 30 minutes to 1 hour on day 0. All patients undergo standard of care surgical resection of tumor on days 2 to 5. Cetuximab: Given IV Cetuximab-IRDye 800CW: Given IV Conventional Surgery: Undergo tumor resection Laboratory Biomarker Analysis: Correlative studies	Total of all reporting groups
Overall Participants	2	1	3
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	1 50%	1 100%	2 66.7%
>=65 years	1 50%	0 0%	1 33.3%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	2 100%	1 100%	3 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	2 100%	1 100%	3 100%
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 50%	0 0%	1 33.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	1 100%	1 33.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 50%	0 0%	1 33.3%
Region of Enrollment (participants) [Number]
United States	2 100%	1 100%	3 100%

Outcome Measures

1. Primary Outcome

Title	Tumor to Background Ratio (TBR)
Description	Tumor to background ratios (TBR) will be generated from still images by comparing the relative fluorescence of normal and tumor tissue. The average fluorescence will be compared to the average fluorescence of the surrounding tissue using the paired student's T test for each specimen.
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 (Cetuximab, Lower Dose Cetuximab-IRDye 800, Surgery)	Cohort 2 (Cetuximab, Higher Dose Cetuximab-IRDye 800, Surgery)
Arm/Group Description	Patients receive cetuximab IV over 30 minutes and a lower dose of cetuximab IRDye800 IV over 30 minutes to 1 hour on day 0. All patients undergo standard of care surgical resection of tumor on days 2 to 5. Cetuximab: Given IV Cetuximab-IRDye 800CW: Given IV Conventional Surgery: Undergo tumor resection Laboratory Biomarker Analysis: Correlative studies	Patients receive cetuximab IV over 30 minutes and a higher dose of cetuximab IRDye800 IV over 30 minutes to 1 hour on day 0. All patients undergo standard of care surgical resection of tumor on days 2 to 5. Cetuximab: Given IV Cetuximab-IRDye 800CW: Given IV Conventional Surgery: Undergo tumor resection Laboratory Biomarker Analysis: Correlative studies
Measure Participants	2	1
Mean (Full Range) [Fluorescence Tumor to background ratio]	1.39	2.65

2. Secondary Outcome

Title	Incidence of Adverse Events
Description	The incidence of serious and non-serious adverse events is reported as the number of adverse events (Grade 2 or higher), as graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Data are reported by number of events by treatment level.
Time Frame	Up to 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 (Cetuximab, Lower Dose Cetuximab-IRDye 800, Surgery)	Cohort 2 (Cetuximab, Higher Dose Cetuximab-IRDye 800, Surgery)
Arm/Group Description	Patients receive cetuximab IV over 30 minutes and a lower dose of cetuximab IRDye800 IV over 30 minutes to 1 hour on day 0. All patients undergo standard of care surgical resection of tumor on days 2 to 5. Cetuximab: Given IV Cetuximab-IRDye 800CW: Given IV Conventional Surgery: Undergo tumor resection Laboratory Biomarker Analysis: Correlative studies	Patients receive cetuximab IV over 30 minutes and a higher dose of cetuximab IRDye800 IV over 30 minutes to 1 hour on day 0. All patients undergo standard of care surgical resection of tumor on days 2 to 5. Cetuximab: Given IV Cetuximab-IRDye 800CW: Given IV Conventional Surgery: Undergo tumor resection Laboratory Biomarker Analysis: Correlative studies
Measure Participants	2	1
Number [Adverse events]	0	0

Adverse Events

Time Frame	30 days
Arm/Group Title	Cohort 1 (Cetuximab, Lower Dose Cetuximab-IRDye 800, Surgery)		Cohort 2 (Cetuximab, Higher Dose Cetuximab-IRDye 800, Surgery)
Arm/Group Description	Patients receive cetuximab IV over 30 minutes and a lower dose of cetuximab IRDye800 IV over 30 minutes to 1 hour on day 0. All patients undergo standard of care surgical resection of tumor on days 2 to 5. Cetuximab: Given IV Cetuximab-IRDye 800CW: Given IV Conventional Surgery: Undergo tumor resection Laboratory Biomarker Analysis: Correlative studies		Patients receive cetuximab IV over 30 minutes and a higher dose of cetuximab IRDye800 IV over 30 minutes to 1 hour on day 0. All patients undergo standard of care surgical resection of tumor on days 2 to 5. Cetuximab: Given IV Cetuximab-IRDye 800CW: Given IV Conventional Surgery: Undergo tumor resection Laboratory Biomarker Analysis: Correlative studies
All Cause Mortality
	Cohort 1 (Cetuximab, Lower Dose Cetuximab-IRDye 800, Surgery)		Cohort 2 (Cetuximab, Higher Dose Cetuximab-IRDye 800, Surgery)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)
Serious Adverse Events
	Cohort 1 (Cetuximab, Lower Dose Cetuximab-IRDye 800, Surgery)		Cohort 2 (Cetuximab, Higher Dose Cetuximab-IRDye 800, Surgery)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1 (Cetuximab, Lower Dose Cetuximab-IRDye 800, Surgery)		Cohort 2 (Cetuximab, Higher Dose Cetuximab-IRDye 800, Surgery)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		1/1 (100%)
Blood and lymphatic system disorders
Anemia	1/2 (50%)	1	1/1 (100%)	1
Investigations
Alanine aminotransferase increased	1/2 (50%)	1	0/1 (0%)	0
Lymphocyte count decreased	1/2 (50%)	1	1/1 (100%)	1
Metabolism and nutrition disorders
Alkalosis	1/2 (50%)	1	0/1 (0%)	0
Hypoalbuminemia	1/2 (50%)	1	1/1 (100%)	1
Hypocalcemia	2/2 (100%)	3	1/1 (100%)	1
Hyponatremia	2/2 (100%)	2	0/1 (0%)	0
Nervous system disorders
Nervous system disorders - Other, Imbalance	1/2 (50%)	1	0/1 (0%)	0
Vascular disorders
Hypertension	1/2 (50%)	1	0/1 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.