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

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

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].

Study Overview

• Status: Completed
• Conditions: Squamous Cell Carcinoma of the Head and Neck; Carcinoma of the Head and Neck
• Intervention / Treatment: Drug: Panitumumab-IRDye800; Device: Explorer Air camera; Device: PDE-NEO II camera; Device: Da Vinci Firefly Imaging System; Device: IGP-ELVIS-v4 Macroscopic Specimen Imager; Device: Vevo 3100 LAZR-X; Device: Pearl Triology Imaging System; Device: Leica fluorescence microscope; Drug: 89-Zirconium (Zr-89) Panitumumab; Device: Pinpoint IR IR9000 fluorescence imaging system (FIS); Device: SPY-PHI IR9000 fluorescence imaging system (FIS); Device: FIS-00 fluorescence imaging system (FIS); Device: Odyssey CLx Imaging System

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute Palo Alto

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tumor-negative Lymph Nodes (by 18F-FDG scan); Participants whose lymph nodes are negative for cancer	Drug: Panitumumab-IRDye800; 30 mg administered intravenously (IV); Other Names: Panitumumab IRDye 800; IRDye800-Panitumumab Conjugate; Device: Explorer Air camera; Fluorescence camera manufactured by SurgVision; Device: PDE-NEO II camera; Medical infrared camera manufactured by Hamamatsu Photonics KK; Device: Da Vinci Firefly Imaging System; Fluorescence-imaging endoscope, mounted or stand-alone, manufactured by Intuitive Surgical Inc; Device: IGP-ELVIS-v4 Macroscopic Specimen Imager; Macroscopic specimen imager manufactured by LI-COR Biosciences; Device: Vevo 3100 LAZR-X; Photoacoustic ultrasound imaging system manufactured by VisualSonics; Device: Pearl Triology Imaging System; Near-infrared fluorescent and bioluminescent imaging system manufactured by LI-COR Biosciences; Device: Leica fluorescence microscope; Fluorescence microscope manufactured by Leica; Drug: 89-Zirconium (Zr-89) Panitumumab; 0.8 to 1.2 mCi (29 to 45 Mbq) administered intravenously (IV); Other Names: 89Zr-panitumumab (SY); 89Zr-labeled Panitumumab (SY); Zr 89-Panitumumab (SY); Device: Pinpoint IR IR9000 fluorescence imaging system (FIS); Handheld fluorescence-imaging endoscope manufactured by Novadaq; Device: SPY-PHI IR9000 fluorescence imaging system (FIS); Handheld fluorescence-imaging endoscope manufactured by Novadaq; Device: FIS-00 fluorescence imaging system (FIS); Fluorescence-imaging system (FIS) manufactured by Hamamatsu Photonics KK; Device: Odyssey CLx Imaging System; Infrared fluorescent-imaging system manufactured by LI-COR Biosciences
Experimental: Tumor-positive Lymph Nodes (by 18F-FDG scan); Participants whose lymph nodes are positive for cancer.	Drug: Panitumumab-IRDye800; 30 mg administered intravenously (IV); Other Names: Panitumumab IRDye 800; IRDye800-Panitumumab Conjugate; Device: Explorer Air camera; Fluorescence camera manufactured by SurgVision; Device: PDE-NEO II camera; Medical infrared camera manufactured by Hamamatsu Photonics KK; Device: Da Vinci Firefly Imaging System; Fluorescence-imaging endoscope, mounted or stand-alone, manufactured by Intuitive Surgical Inc; Device: IGP-ELVIS-v4 Macroscopic Specimen Imager; Macroscopic specimen imager manufactured by LI-COR Biosciences; Device: Vevo 3100 LAZR-X; Photoacoustic ultrasound imaging system manufactured by VisualSonics; Device: Pearl Triology Imaging System; Near-infrared fluorescent and bioluminescent imaging system manufactured by LI-COR Biosciences; Device: Leica fluorescence microscope; Fluorescence microscope manufactured by Leica; Drug: 89-Zirconium (Zr-89) Panitumumab; 0.8 to 1.2 mCi (29 to 45 Mbq) administered intravenously (IV); Other Names: 89Zr-panitumumab (SY); 89Zr-labeled Panitumumab (SY); Zr 89-Panitumumab (SY); Device: Pinpoint IR IR9000 fluorescence imaging system (FIS); Handheld fluorescence-imaging endoscope manufactured by Novadaq; Device: SPY-PHI IR9000 fluorescence imaging system (FIS); Handheld fluorescence-imaging endoscope manufactured by Novadaq; Device: FIS-00 fluorescence imaging system (FIS); Fluorescence-imaging system (FIS) manufactured by Hamamatsu Photonics KK; Device: Odyssey CLx Imaging System; Infrared fluorescent-imaging system manufactured by LI-COR Biosciences

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
89Zr-panitumumab and 18F-FDG False-negatives	The value of experimental 89Zr-panitumumab as a radiologic label was assessed as the number of lymph nodes (LNs) that have false-negative results. A false-negative result in this study is one that does not indicate that cancer is present in the lymph node, when histopathologic evaluation confirms the presence of cancer in the lymph nodes. The outcome is reported as the number of false-negative lymph nodes observed after systemic labeling with 89Zr-panitumumab and 18F-FDG, an established agent for this use. The outcome results are numbers without dispersion.	up to 5 days
Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of 89Zr-panitumumab and 18F-FDG	The value of experimental 89Zr-panitumumab as a radiologic label was assessed by determining the positive predictive value (PPV) and the negative predictive value (NPV). PPV is a measure of extent that positive-labeled samples that were actually cancer, expressed as a proportion (ratio) of the number of positive-labeled samples vs samples positive by histopathology (positive label/positive histopathology). NPV is a measure of extent that negative-labeled samples (not positive) that were actually NOT cancer, expressed as a proportion (ratio) of the number of negative-labeled samples vs samples NOT positive by histopathology (negative label/negative histopathology). The closer the proportions are to 1, the better the predictive value. The outcome is reported as the PPV and NPV of 89Zr-panitumumab and 18F-fluorodeoxyglucose (18F-FDG), an established agent for this use. The outcome results are ratios, numbers without dispersion.	up to 5 days

Collaborators and Investigators

• Sponsor: Andrei Iagaru
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Andrei Iagaru, MD, Stanford Medicine at Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2019
• Primary Completion (Actual): December 11, 2020
• Study Completion (Actual): August 9, 2021

Study Registration Dates

• First Submitted: November 5, 2018
• First Submitted That Met QC Criteria: November 5, 2018
• First Posted (Actual): November 7, 2018

Study Record Updates

• Last Update Posted (Actual): May 19, 2023
• Last Update Submitted That Met QC Criteria: April 24, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Head and Neck Cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Carcinoma; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents; Antineoplastic Agents, Immunological; Panitumumab
• Other Study ID Numbers: IRB-41878 (stanford-IRB); P30CA124435 (U.S. NIH Grant/Contract); R01CA190306 (U.S. NIH Grant/Contract); NCI-2018-02270 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); ENT0066 (Other Identifier: OnCore Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No