Panitumumab-IRDye800 and 89Zr-Panitumumab in Identifying Metastatic Lymph Nodes in Patients With Squamous Cell Head and Neck Cancer

Study Overview
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Brief Summary
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This study evaluates how well panitumumab-IRDye800 and 89Zr-panitumumab work in identifying cancer that has spread to the lymph nodes in patients with squamous cell head and neck cancer. Panitumumab-IRDye800 is a drug that contains a dye molecule that fluoresces during surgery to indicate cancerous tissue. 89Zr-panitumumab is a drug that contains a small amount of radiation, which makes it visible in positron emission tomography (PET) scans. PET scans make detailed, computerized pictures of areas inside the body where the drug is used. Giving panitumumab-IRDye800 and 89Zr-panitumumab to patients with head and neck cancer may help doctors find metastatic lymph nodes better than current methods [positron emission tomography (PET); computed tomography (CT); magnetic imaging resonance (MRI), or combinations].

Detailed Description
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For patients with head and neck cancer, detection of malignant cells within nearby lymph nodes (LNs) is an important measure of the extent and severity of the cancer. LNs are a key immunologic organ involved in overall immune surveillance. Historically, LN or LNs were harvested before the surgery of curative intent, evaluated pathologically, and then tumor status of the harvested LNs were utilized to inform the individual surgical plan. These LNs became known as sentinel lymph nodes. In recent years, techniques have been developed to utilize peritumoral injection (around the tumor) of tumor labels that could identify tumor in the LNs without biopsy, ie, only LNs that were tumor-positive would be removed. However, in some patients, this technique could be limited by the location of the primary cancer. Effective and sensitive systemically-administered labels would be a significant advancement. The systemically-administered label 18F-fluorodeoxyglucose (18F-FDG), detected by positron emission tomography / computed tomography (PET/CT) and/or PET / magnetic imaging resonance (PET/MRI) radiologic scans and representing current regular medical care, has provided improvement in detection of cancer-positive LNs. However, further enhancements may be possible. Participants with squamous cell carcinoma of the head and neck (SCCHN) and scheduled to undergo regular medical care surgery with curative intent, were assigned to 2 study groups on the basis of whether regular medical care scans using 18F-FDG PET/CT or PET/MRI had indicated that cancer was suspected in the lymph nodes (LN+ or cN+), or without suspected cancer in the lymph nodes (LN- or cN0). Following the 18F-FDG, and prior to surgery, 89Zr-panitumumab was systemically administered by intravenous infusion, and a PET-CT imaging scan was conducted. Research imaging will be performed intraoperatively using optical imaging devices and a high-energy gamma probe. Subsequently, the excised tissue will evaluated ex vivo (back table) using radioactive (89Zr-panitumumab) and fluorescence (panitumumab-IRDye800) imaging techniques. Regular medical care surgical excision of the tumor and adjacent LN was conducted on Day 2 to 5. After surgery, patients are followed up at 15 and 30 days. PRIMARY OBJECTIVES: I. Determine the sensitivity and specificity of zirconium(89Zr)-panitumumab (89Zr-panitumumab) for the detection of tumor-involved regional lymph nodes. SECONDARY OBJECTIVES: I. Determine the number (proportion) of lymph nodes determined to be tumor positive by histological and/or pathological evaluation that were NOT predicted tumor-positive by 89Zr-panitumumab labeling. EXPLORATORY OBJECTIVES: I. Determine the sensitivity and specificity of panitumumab-IRDye800 for the detection of tumor-involved regional lymph nodes. II. Determine the number (proportion) of lymph nodes determined to be tumor positive by histological and/or pathological evaluation that were NOT predicted tumor-positive by panitumumab-IRDye800 labeling.

Official Title
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Pilot Study Evaluating Panitumumab-IRDye800 and 89Zr-Panitumumab for Dual-Modality Imaging for Nodal Staging in Head and Neck Cancer

Conditions
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Squamous Cell Carcinoma of the Head and Neck, Carcinoma of the Head and Neck

Intervention / Treatment
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* Drug: Panitumumab-IRDye800
* Drug: 89-Zirconium (Zr-89) Panitumumab
* Device: Pinpoint IR IR9000 fluorescence imaging system (FIS)
* Device: SPY-PHI IR9000 fluorescence imaging system (FIS)
* Device: Explorer Air camera
* Device: PDE-NEO II camera
* Device: FIS-00 fluorescence imaging system (FIS)
* Device: Da Vinci Firefly Imaging System
* Device: IGP-ELVIS-v4 Macroscopic Specimen Imager
* Device: Vevo 3100 LAZR-X
* Device: Pearl Triology Imaging System
* Device: Odyssey CLx Imaging System
* Device: Leica fluorescence microscope


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy confirmed diagnosis of squamous cell carcinoma of the head and neck. Subjects diagnosed with any T stage, any subsite within the head and neck that are scheduled to undergo surgical resection. Subjects with recurrent disease or a new primary will be allowed. Planned standard of care surgery with curative intent for squamous cell carcinoma. Hemoglobin ≥ 9 gm/dL. White blood cell count > 3000/mm³. Platelet count ≥ 100,000/mm³. Serum creatinine ≤ 1.5 times upper reference range. Exclusion Criteria: Myocardial infarction (MI); cerebrovascular accident (CVA); uncontrolled congestive heart failure (CHF); significant liver disease; or unstable angina within 6 months prior to enrollment. Previous bilateral neck dissection. History of infusion reactions to monoclonal antibody therapies. Pregnant or breastfeeding. Magnesium or potassium lower than the normal institutional values. 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. Severe renal disease or anuria. Known hypersensitivity to deferoxamine or any of its components.

Ages Eligible for Study
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Minimum Age: 19 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: Tumor-negative Lymph Nodes (by 18F-FDG scan)<br>Participants whose lymph nodes are negative for cancer | Drug: Panitumumab-IRDye800<br>* 30 mg administered intravenously (IV)<br>* Other names: IRDye800-Panitumumab Conjugate;Drug: 89-Zirconium (Zr-89) Panitumumab<br>* 0.8 to 1.2 mCi (29 to 45 Mbq) administered intravenously (IV)<br>* Other names: Zr 89-Panitumumab (SY);Device: Pinpoint IR IR9000 fluorescence imaging system (FIS)<br>* Handheld fluorescence-imaging endoscope manufactured by Novadaq<br>Device: SPY-PHI IR9000 fluorescence imaging system (FIS)<br>* Handheld fluorescence-imaging endoscope manufactured by Novadaq<br>Device: Explorer Air camera<br>* Fluorescence camera manufactured by SurgVision<br>Device: PDE-NEO II camera<br>* Medical infrared camera manufactured by Hamamatsu Photonics KK<br>Device: FIS-00 fluorescence imaging system (FIS)<br>* Fluorescence-imaging system (FIS) manufactured by Hamamatsu Photonics KK<br>Device: Da Vinci Firefly Imaging System<br>* Fluorescence-imaging endoscope, mounted or stand-alone, manufactured by Intuitive Surgical Inc<br>Device: IGP-ELVIS-v4 Macroscopic Specimen Imager<br>* Macroscopic specimen imager manufactured by LI-COR Biosciences<br>Device: Vevo 3100 LAZR-X<br>* Photoacoustic ultrasound imaging system manufactured by VisualSonics<br>Device: Pearl Triology Imaging System<br>* Near-infrared fluorescent and bioluminescent imaging system manufactured by LI-COR Biosciences<br>Device: Odyssey CLx Imaging System<br>* Infrared fluorescent-imaging system manufactured by LI-COR Biosciences<br>Device: Leica fluorescence microscope<br>* Fluorescence microscope manufactured by Leica<br>|
| Experimental: Tumor-positive Lymph Nodes (by 18F-FDG scan)<br>Participants whose lymph nodes are positive for cancer. | Drug: Panitumumab-IRDye800<br>* 30 mg administered intravenously (IV)<br>* Other names: IRDye800-Panitumumab Conjugate;Drug: 89-Zirconium (Zr-89) Panitumumab<br>* 0.8 to 1.2 mCi (29 to 45 Mbq) administered intravenously (IV)<br>* Other names: Zr 89-Panitumumab (SY);Device: Pinpoint IR IR9000 fluorescence imaging system (FIS)<br>* Handheld fluorescence-imaging endoscope manufactured by Novadaq<br>Device: SPY-PHI IR9000 fluorescence imaging system (FIS)<br>* Handheld fluorescence-imaging endoscope manufactured by Novadaq<br>Device: Explorer Air camera<br>* Fluorescence camera manufactured by SurgVision<br>Device: PDE-NEO II camera<br>* Medical infrared camera manufactured by Hamamatsu Photonics KK<br>Device: FIS-00 fluorescence imaging system (FIS)<br>* Fluorescence-imaging system (FIS) manufactured by Hamamatsu Photonics KK<br>Device: Da Vinci Firefly Imaging System<br>* Fluorescence-imaging endoscope, mounted or stand-alone, manufactured by Intuitive Surgical Inc<br>Device: IGP-ELVIS-v4 Macroscopic Specimen Imager<br>* Macroscopic specimen imager manufactured by LI-COR Biosciences<br>Device: Vevo 3100 LAZR-X<br>* Photoacoustic ultrasound imaging system manufactured by VisualSonics<br>Device: Pearl Triology Imaging System<br>* Near-infrared fluorescent and bioluminescent imaging system manufactured by LI-COR Biosciences<br>Device: Odyssey CLx Imaging System<br>* Infrared fluorescent-imaging system manufactured by LI-COR Biosciences<br>Device: Leica fluorescence microscope<br>* Fluorescence microscope manufactured by Leica<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of Tumor in Lymph Nodes by 18F-FDG and 89Zr-panitumumab Labeling | The ability of 89Zr-panitumumab and 18F-fluorodeoxyglucose (18F-FDG) to detect tumor in lymph nodes were assessed on the basis of radiologic scans and histopathologic evaluation of excised lymph nodes (LNs). The histopathologic assessment was considered the definitive, regular medical care, assessment. The outcome is reported by study group as the number of LNs that were identified as tumor-positive by 18F-FDG- and 89Zr-panitumumab, stratified by the tumor-positivity as assessed by histopathology, and expressed as the number of LNs that were tumor-positive by both, negative for both, or positive for one and not the other. Results are also provided by study group for the number of LNs that tumor-positive by both 18F-FDG- and 89Zr-panitumumab, negative for both, or positive for one and not the other. The outcome is numbers without dispersion | up to 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and Specificity of 89Zr-panitumumab, 18F-FDG, and Panitumumab-IRDye800 | The value of 89Zr-panitumumab and panitumumab-IRDye800 as a label for cancer cells (radiologic or fluorescent, respectively), was assessed by the sensitivity and specificity for the detection of tumor cells in lymph nodes near the tumor. 18F-fluorodeoxyglucose (18F-FDG), an established agent for this use, was also assessed. Sensitivity was assessed as the true positive rate of paired measurements, expressed as the proportion (ratio) of the number of specimens positive by histopathology also positive by the test method (test:histopathology). Specificity is the true negative rate, the proportion of the number of specimens negative by histopathology also negative by the test method. The closer the proportions are to 1, the greater the sensitivity or specificity. The outcome is reported as the sensitivity and specificity of 89Zr-panitumumab, panitumumab-IRDye800, and 18F-fluorodeoxyglucose (18F-FDG). The outcome results are ratios, a number without dispersion. | up to 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and Neck Cancer