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

Study Overview
=================
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.

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.

Official Title
-----------------
Open-Label Study Evaluating Cetuximab-IRDye800 as an Optical Imaging Agent to Detect Neoplasms During Neurosurgical Procedures

Conditions
-----------------
Brain Neoplasm, Malignant Glioma

Intervention / Treatment
-----------------
* Biological: Cetuximab
* Drug: Cetuximab-IRDye 800CW
* Procedure: Tumor resection


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50 mg cetuximab-IRDye 800<br>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<br>* Administered intravenously (IV)<br>* Other names: IMC-C225;Drug: Cetuximab-IRDye 800CW<br>* Administered intravenously (IV)<br>* Other names: Cetuximab-IRDye800CW;Procedure: Tumor resection<br>* Standard of care treatment<br>* Other names: Conventional Surgery;|
| Experimental: 100 mg cetuximab-IRDye 800<br>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<br>* Administered intravenously (IV)<br>* Other names: IMC-C225;Drug: Cetuximab-IRDye 800CW<br>* Administered intravenously (IV)<br>* Other names: Cetuximab-IRDye800CW;Procedure: Tumor resection<br>* Standard of care treatment<br>* Other names: Conventional Surgery;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor to Background Ratio (TBR) | 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. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events | 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. | Up to 30 days |