NCT03733210

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

Completed Phase 1 Results posted Last updated 19 May 2023

What this trial tests

Phase 1 trial testing Panitumumab-IRDye800 in Squamous Cell Carcinoma of the Head and Neck in 14 participants. Completed in 9 August 2021.

Timeline

7 January 2019

Primary endpoint
11 December 2020

9 August 2021

Quick facts

Lead sponsor	Andrei Iagaru
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	diagnostic
Enrollment	14
Start date	7 January 2019
Primary completion	11 December 2020
Estimated completion	9 August 2021
Sites	1 location across United States

Drugs / interventions tested

• Panitumumab-IRDye800 — full drug profile →
• 89-Zirconium (Zr-89) Panitumumab — full drug profile →
• Pinpoint IR IR9000 fluorescence imaging system (FIS)
• SPY-PHI IR9000 fluorescence imaging system (FIS)
• Explorer Air camera
• PDE-NEO II camera
• FIS-00 fluorescence imaging system (FIS)
• Da Vinci Firefly Imaging System
• IGP-ELVIS-v4 Macroscopic Specimen Imager
• Vevo 3100 LAZR-X
• Pearl Triology Imaging System
• Odyssey CLx Imaging System
• Leica fluorescence microscope

Conditions studied

• Squamous Cell Carcinoma of the Head and Neck — all drugs for Squamous Cell Carcinoma of the Head and Neck →
• Carcinoma of the Head and Neck — all drugs for Carcinoma of the Head and Neck →

Sponsor

Andrei Iagaru — full company profile →

Who can join

19 and older, any sex, with Squamous Cell Carcinoma of the Head and Neck or Carcinoma of the Head and Neck. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Detection of Tumor in Lymph Nodes by 18F-FDG and 89Zr-panitumumab Labeling Primary · up to 5 days

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 positi

89Zr-panitumumab-positive & pathology-positive

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	0
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	4

89Zr-panitumumab-positive & pathology-negative

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	0
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	0

89Zr-panitumumab-negative & pathology-positive

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	0
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	6

89Zr-panitumumab-negative & pathology-negative

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	5
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	6

18F-FDG-positive & pathology-positive

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	0
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	7

18F-FDG-positive & pathology-negative

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	0
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	3

18F-FDG-negative & pathology-positive

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	0
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	2

18F-FDG-negative & pathology-negative

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	6
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	6

Sensitivity and Specificity of 89Zr-panitumumab, 18F-FDG, and Panitumumab-IRDye800 Secondary · up to 5 days

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 propor

89Zr-panitumumab Sensitivity

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	0
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	0.4

89Zr-panitumumab Specificity

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	0
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	1.0

Panitumumab-IRDye800 Sensitivity

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	0
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	1.0

Panitumumab-IRDye800 Specificity Panitumumab-IRDye800 Specificity

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	0
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	1.0

18F-FDG Sensitivity

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	0
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	0.78

18F-FDG Specificity

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	0
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	0.67

89Zr-panitumumab and 18F-FDG False-negatives Secondary · up to 5 days

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.

89Zr-panitumumab False-negatives

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	0
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	6

18F-FDG False-negatives

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	0
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	2

Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of 89Zr-panitumumab and 18F-FDG Secondary · up to 5 days

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

89Zr-panitumumab Positive Predictive Value (PPV)

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	0
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	0.4

89Zr-panitumumab Negative Predictive Value (NPV)

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	0
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	1.0

18F-FDG Positive Predictive Value (PPV)

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	0
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	0.78

18F-FDG Negative Predictive Value (NPV)

Group	Value	95% CI
Tumor-negative Lymph Nodes (by 18F-FDG Scan)	0
Tumor-positive Lymph Nodes (by 18F-FDG Scan)	0.67

Adverse events — posted to ClinicalTrials.gov

Time frame: 30 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Tumor-negative Lymph Nodes (by 18F-FDG Scan)

Serious: 1/7 (14%)

Deaths: 0/7

Tumor-positive Lymph Nodes (by 18F-FDG Scan)

Serious: 0/7 (0%)

Deaths: 0/7

Serious adverse events (1 terms)

Reaction	System	Tumor-negative Lymph Nodes…	Tumor-positive Lymph Nodes…
Sepsis	Infections and infestations	—	—

Other adverse events (42 terms — click to expand)

Reaction	System	Tumor-negative Lymph Nodes…	Tumor-positive Lymph Nodes…
Hypertension	Vascular disorders	—	—
Hypotension	Vascular disorders	—	—
Somnolence	Nervous system disorders	—	—
Hematuria	Renal and urinary disorders	—	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—
Anemia	Blood and lymphatic system disorders	—	—
Atrial flutter	Cardiac disorders	—	—
Mobitz (type) II atrioventricular block	Cardiac disorders	—	—
Other	Cardiac disorders	—	—
Sinus bradycardia	Cardiac disorders	—	—
Hypothyroidism	Endocrine disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Edema face	General disorders	—	—
Fatigue	General disorders	—	—
Non-cardiac chest pain	General disorders	—	—
Abdominal infection	Infections and infestations	—	—
Wound infection	Infections and infestations	—	—
Wound complication	Injury, poisoning and procedural complications	—	—
Electrocardiogram QT corrected interval prolonged	Investigations	—	—
Other, hypercarbia	Investigations	—	—
Anorexia	Metabolism and nutrition disorders	—	—
Hypokalemia	Metabolism and nutrition disorders	—	—
Other, refeeding syndrome, mild	Metabolism and nutrition disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Neck pain	Musculoskeletal and connective tissue disorders	—	—
Aphonia	Nervous system disorders	—	—
Dizziness	Nervous system disorders	—	—
Facial muscle weakness	Nervous system disorders	—	—
Facial nerve disorder	Nervous system disorders	—	—
Headache	Nervous system disorders	—	—
Hypoglossal nerve disorder	Nervous system disorders	—	—
Aspiration	Respiratory, thoracic and mediastinal disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—
Other, fistula, nasal-oral, right	Respiratory, thoracic and mediastinal disorders	—	—
Pulmonary edema	Respiratory, thoracic and mediastinal disorders	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—
Other, - Jackson-Pratt drain with serous drainage and tracheostomy site with mucinous secretion	Surgical and medical procedures	—	—
Other, extravasation along anterior abdominal wall consistent with gastrostomy tube leak	Surgical and medical procedures	—	—

Most-reported serious reactions: Sepsis.

Data from ClinicalTrials.gov NCT03733210 adverse events section.

Sponsor's own description

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 \[positron emission tomography (PET); computed tomography (CT); magnetic imaging resonance (MRI), or combinations\].

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Fluorescent Molecular Imaging Can Improve Intraoperative Sentinel Margin Detection in Oral Squamous Cell Carcinoma.
   Krishnan G, van den Berg NS, Nishio N, Kapoor S, et al · · 2022 · cited 28× · PMID 35027369 · DOI 10.2967/jnumed.121.262235
2. PET and SPECT Imaging of the EGFR Family (RTK Class I) in Oncology.
   Rinne SS, Orlova A, Tolmachev V. · · 2021 · cited 22× · PMID 33915894 · DOI 10.3390/ijms22073663
3. Monoclonal Antibodies for Targeted Fluorescence-Guided Surgery: A Review of Applicability across Multiple Solid Tumors.
   Giuliani S, Paraboschi I, McNair A, Smith M, et al · · 2024 · cited 14× · PMID 38473402 · DOI 10.3390/cancers16051045
4. Radiometals in Imaging and Therapy: Highlighting Two Decades of Research.
   Sharma S, Pandey MK. · · 2023 · cited 13× · PMID 37895931 · DOI 10.3390/ph16101460
5. Potential of uPAR, αvβ6 Integrin, and Tissue Factor as Targets for Molecular Imaging of Oral Squamous Cell Carcinoma: Evaluation of Nine Targets in Primary Tumors and Metastases by Immunohistochemistry.
   Lawaetz M, Christensen A, Juhl K, Karnov K, et al · · 2023 · cited 12× · PMID 36835265 · DOI 10.3390/ijms24043853
6. Biotherapeutic Antibodies for the Treatment of Head and Neck Cancer: Current Approaches and Future Considerations of Photothermal Therapies.
   Al Qaraghuli MM. · · 2020 · cited 10× · PMID 33324546 · DOI 10.3389/fonc.2020.559596
7. Infrared Fluorescence-guided Surgery for Tumor and Metastatic Lymph Node Detection in Head and Neck Cancer.
   White HW, Naveed AB, Campbell BR, Lee YJ, et al · · 2024 · cited 6× · PMID 38940689 · DOI 10.1148/rycan.230178
8. Enhancement of Immunotherapies in Head and Neck Cancers Using Biomaterial-Based Treatment Strategies.
   Sunga GM, Hartgerink J, Sikora AG, Young S. · · 2023 · cited 3× · PMID 37183412 · DOI 10.1089/ten.tec.2023.0090