Panitumumab-IRDye800 in Diagnosing Participants With Malignant Glioma Undergoing Surgery

Study Overview
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Brief Summary
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The phase I/II trial studies the side effects and best dose of panitumumab-IRDye800 in diagnosing participants with malignant glioma who undergo surgery. Panitumumab-IRDye800 can attach to tumor cells and make them more visible using a special camera during surgery, which may help surgeons better distinguish tumor cells from normal brain tissue and identify small tumors that cannot be seen using current imaging methods.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine/verify the safety and pharmacokinetic profile of panitumumab conjugated to the optical dye IRDye800CW (panitumumab-IRDye800), as an imaging agent in patients undergoing surgery for malignant glioma. SECONDARY OBJECTIVES: I. Determine the efficacy of panitumumab IRDye800 in identifying malignant glioma compared to surrounding normal central nervous system tissue. II. Determine whether a loading dose of panitumumab is necessary to achieve an effective tumor-to-background ratio. III. Determine the optimal timing of the surgical procedure to maximize the tumor-to-background ratio. OUTLINE: This is a phase I, dose escalation study of panitumumab-IRDye800 followed by a phase II study.

Official Title
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Phase I/II, Open-Label Study Evaluating the Efficacy and Pharmacokinetics of Panitumumab-IRDye800 as an Optical Imaging Agent to Detect Neoplasms During Neurosurgical Procedures

Conditions
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Malignant Brain Neoplasm, Malignant Glioma

Intervention / Treatment
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* Procedure: Near-Infrared Fluorescence Imaging
* Biological: Panitumumab
* Drug: Panitumumab-IRDye800
* Device: POINPOINT-IR9000


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with suspected brain tumors undergoing surgical removal as their standard of care will be eligible; these may include subjects' status post chemotherapy and/or radiation or subjects who have undergone diagnostic biopsy for their original diagnosis and are assessed to be candidates for resection Subjects must be eligible for resection as determined by the operating surgeon Platelet count ≥ 75,000/mm^3 Exclusion Criteria: Received an investigational drug within 30 days prior to first dose of panitumumab-IRDye800 Myocardial infarction (MI); cerebrovascular accident (CVA); uncontrolled congestive heart failure (CHF); significant liver disease; or unstable angina within 6 months prior to enrollment History of infusion reactions to monoclonal antibody therapies Pregnant or breastfeeding Evidence of corrected QT (QTc) prolongation on pre-treatment electrocardiography (ECG) (greater than 440ms in males or greater than 460ms in females) Thyroid-stimulating hormone (TSH) ≥ 13 micro international units/mL Magnesium, potassium and calcium < the lower limit of normal per institution normal lab values Other lab values that in the opinion of the primary surgeon would prevent surgical resection Subjects receiving class IA (quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents Subjects with a history or evidence of interstitial pneumonitis or pulmonary fibrosis Subjects not deemed to be appropriate candidates for optimal resection of tumor based on location, involvement of eloquent brain, satellite lesions, or other factors not specifically listed here

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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: Cohort 1 -50mg panitumumab-IRDye800<br>A panitumumab-IRDye800 dose of 50mg (Cohort 1) with or without a 100 mg loading dose of unlabeled panitumumab will be injected 1 to 5 days before the planed standard of care surgery. Participants then undergo NIR imaging during standard of care surgery 1-5 days after receiving panitumumab-IRDye800. | Procedure: Near-Infrared Fluorescence Imaging<br>* Undergo NIR imaging<br>* Other names: NIR Optical Imaging;Biological: Panitumumab<br>* Given IV<br>* Other names: Vectibix;Drug: Panitumumab-IRDye800<br>* Given IV<br>* Other names: RDye800-Panitumumab Conjugate;Device: POINPOINT-IR9000<br>* Intraoperative camera capable of exciting and detecting near infrared (NIR) dyes. Imaging will be performed on subjects during surgery and/or on ex-vivo resected tissues in the surgery suite (back table).<br>|
| Experimental: Cohort 2 -100mg panitumumab-IRDye800<br>A panitumumab-IRDye800 dose of 100mg (Cohort 2) with or without a 100 mg loading dose of unlabeled panitumumab will be injected 1 to 5 days before the planed standard of care surgery. Participants then undergo NIR imaging during standard of care surgery 1-5 days after receiving panitumumab-IRDye800. | Procedure: Near-Infrared Fluorescence Imaging<br>* Undergo NIR imaging<br>* Other names: NIR Optical Imaging;Biological: Panitumumab<br>* Given IV<br>* Other names: Vectibix;Drug: Panitumumab-IRDye800<br>* Given IV<br>* Other names: RDye800-Panitumumab Conjugate;Device: POINPOINT-IR9000<br>* Intraoperative camera capable of exciting and detecting near infrared (NIR) dyes. Imaging will be performed on subjects during surgery and/or on ex-vivo resected tissues in the surgery suite (back table).<br>|
| Experimental: Cohort 3 -100mg panitumumab-IRDye800<br>Cohort 3 dose will be determined based on Cohort 1 and Cohort 2, with or without a 100 mg loading dose of unlabeled panitumumab will be injected 1 to 5 days before the planed standard of care surgery | Procedure: Near-Infrared Fluorescence Imaging<br>* Undergo NIR imaging<br>* Other names: NIR Optical Imaging;Biological: Panitumumab<br>* Given IV<br>* Other names: Vectibix;Drug: Panitumumab-IRDye800<br>* Given IV<br>* Other names: RDye800-Panitumumab Conjugate;Device: POINPOINT-IR9000<br>* Intraoperative camera capable of exciting and detecting near infrared (NIR) dyes. Imaging will be performed on subjects during surgery and/or on ex-vivo resected tissues in the surgery suite (back table).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of grade 2 or higher adverse events which have been determined to be clinically significant and definitely, probably, or possibly related to the study treatment, graded according to Common Terminology Criteria for Adverse Effects (CTCAE) v. 4.0 | Descriptive statistical analysis of subject disposition, baseline characteristics, exposure to study drug, and adverse events will be performed. Descriptive statistics for continuous data will include mean, standard deviation, median, minimum, maximum, and inter-quartile values. Frequencies and percentages will be used to summarize categorical data. | Up to 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor to background ratio (TBR) | TBR is defined as the fluorescence intensity of tumor tissue compared to that or normal surrounding tissue as determined by ex vivo pathological imaging. Will be analyzed with the individual specimen as the unit of analysis using the Wilcoxon signed rank test. | 30 days from study treatment | 
| Panitumumab Loading Dose | The fluorescence intensity of tissue obtained from patients undergoing surgery will be evaluated as an indicator of whether or not the loading dose of panitumumab is necessary to achieve an effective tumor-to-background ratio (TBR). The Fluorescence intensity of tissue will be assessed on the specimens collected on the day of surgery (Day 1-5 Post infusion), in group a vs group b, for Cohorts 1 and 2, in order to determine the tumor-to-background ratio (TBR). The outcome will be expressed as TBR by group and cohort. TBR will be reported as means +/- STD. | 30 days | 
| Optimal Timing of Surgical Procedure | The fluorescence intensity of tissue collected at surgery will be measured 1 to 5 days after infusion, and the outcome will be assessed as highest daily mean tumor-to-background ratio (TBR), with standard deviation. The tissue analysis to obtain the outcome data will occur within 1 year from surgery. | 1 year |