Dual Imaging for Head and Neck Cancer

Overseen By Nicole Jones

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Vanderbilt-Ingram Cancer Center

Must not be taking: Antiarrhythmics

Disqualifiers: MI, CHF, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 1 week

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial evaluates the safety and effectiveness of using two imaging techniques, indium In 111 panitumumab (111In-panitumumab) with single photon emission computed tomography (SPECT)/computed tomography (CT) and panitumumab-IRDye800 fluorescence imaging during surgery (intraoperative), to detect disease in patients with head and neck cancer. 111In-panitumumab is an imaging agent made of a monoclonal antibody that has been labeled with a radioactive molecule called indium In 111. The agent targets and binds to receptors on tumor cells. This allows the cells to be visualized and assessed with SPECT/CT imaging techniques. SPECT is special type of CT scan in which a small amount of a radioactive drug is injected into a vein and a scanner is used to make detailed images of areas inside the body where the radioactive material is taken up by the cells. CT is an imaging technique for examining structures within the body by scanning them with x-rays and using a computer to construct a series of cross-sectional scans along a single axis. Panitumumab-IRDye800 is an imaging agent composed of panitumumab, a monoclonal antibody, linked to a fluorescent dye called IRDye800. Upon administration, panitumumab-IRDye800 targets and binds to receptors on tumor cells. This allows the tumor cells to be detected using fluorescence imaging during surgery. Adding 111In-panitumumab SPECT/CT imaging to intraoperative panitumumab-IRDye800 fluorescence imaging may be more effective at detecting disease in patients with head and neck cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking certain heart rhythm medications (like quinidine, procainamide, dofetilide, amiodarone, or sotalol), you may not be eligible to participate.

What data supports the effectiveness of the drug Indium In 111 Panitumumab for head and neck cancer?

Research shows that panitumumab-IRDye800, a component of the drug, is effective in identifying cancerous lymph nodes during surgery by using a special imaging technique. This helps doctors see and remove cancer more accurately, which could improve treatment outcomes for head and neck cancer patients. ^{1 2 3 4 5}

Is the dual imaging treatment using panitumumab-IRDye800CW safe for humans?

Research shows that panitumumab-IRDye800CW is generally safe for humans, with minimal side effects. In a study with patients having head and neck cancer, there were no serious side effects, and only one mild reaction was reported, suggesting it is well-tolerated. ^{1 2 3 5 6}

How does the dual imaging treatment for head and neck cancer differ from other treatments?

This treatment uses a special imaging technique that combines antibodies with a fluorescent dye to help surgeons see cancerous tissues more clearly during surgery. This approach is unique because it allows for better identification of cancerous lymph nodes, potentially improving surgical outcomes compared to traditional methods that rely solely on visual inspection. ^{1 2 3 7 8}

Research Team

Eben Rosenthal, MD

Principal Investigator

Vanderbilt University/Ingram Cancer Center

Eligibility Criteria

This trial is for adults over 19 with any stage of head and neck squamous cell carcinoma, scheduled for surgery. It includes those with recurrent disease or a new primary cancer who can sign consent. Excluded are pregnant individuals, those with certain heart risks, severe kidney issues, recent serious cardiovascular events, allergies to iodine or past bad reactions to monoclonal antibodies.

Inclusion Criteria

I am 19 years old or older.

I have been diagnosed with squamous cell carcinoma in my head or neck.

I am scheduled for surgery to remove a tumor in my head or neck, including if it's a recurrence or a new primary tumor.

Exclusion Criteria

Magnesium or potassium lower than the normal institutional values

Evidence of QT prolongation on pretreatment electrocardiogram (ECG) (greater than 440 ms in males or greater than 450 ms in females)

History of allergies to iodine

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive panitumumab-IRDye800 IV over 15 minutes followed by 111In-panitumumab IV on day 0, then undergo SPECT/CT between days 1 and 5, prior to standard of care surgical resection with fluorescence imaging

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 days

1 visit (in-person)

Treatment Details

Interventions

• Indium In 111 Panitumumab
• Panitumumab-IRDye800

Trial Overview The trial tests two imaging techniques in detecting head and neck cancer during surgery: a radioactive agent (111In-panitumumab) used with SPECT/CT scans and a fluorescent dye-linked antibody (panitumumab-IRDye800). The goal is to see if combining these methods improves disease detection.

Participant Groups

Group I: Diagnostic (panitumumab-IRDye800, 111In-panitumumab, SPECT/CT) Experimental Treatment 6 Interventions

Patients receive panitumumab-IRDye800 IV over 15 minutes followed by 111In-panitumumab IV on day 0. Patients then undergo SPECT/CT between days 1 and 5, prior to standard of care surgical resection with fluorescence imaging.

Who Is Running the Clinical Trial?

Vanderbilt-Ingram Cancer Center

Lead Sponsor

Trials

221

Recruited

64,400+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

The study demonstrated that the fluorescently labeled antibodies cetuximab-IRDye800CW and panitumumab-IRDye800CW are safe for use in surgical imaging, with minimal toxicities observed in 27 patients with head and neck squamous cell carcinoma.

Both antibodies showed similar pharmacodynamic properties, and no significant safety concerns were raised, indicating potential for other therapeutic antibodies to be repurposed for imaging with limited preclinical data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of panitumumab-IRDye800CW and cetuximab-IRDye800CW for fluorescence-guided surgical navigation in head and neck cancers. Gao, RW., Teraphongphom, N., de Boer, E., et al.[2019]

In a study involving 24 patients with head and neck squamous cell carcinoma, a fixed dose of 50 mg of the fluorescently labeled antibody panitumumab-IRDye800CW was identified as the optimal dose for enhancing fluorescence during surgery.

The study found that reducing the time between infusion and surgery to within 2 days significantly increased the fluorescence intensity of the tumors, suggesting that timing is crucial for effective imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal Dosing Strategy for Fluorescence-Guided Surgery with Panitumumab-IRDye800CW in Head and Neck Cancer. Nishio, N., van den Berg, NS., van Keulen, S., et al.[2021]

Photoacoustic molecular imaging (PAMI) using panitumumab conjugated to IRDye800CW effectively identified metastatic lymph nodes (LNs) in patients with head and neck squamous cell carcinoma (HNSCC), showing a 5-fold higher signal intensity in metastatic LNs compared to benign ones.

The study analyzed 53 LNs and found that PAMI could distinguish metastatic from benign LNs with high accuracy, achieving an area under the receiver-operating-characteristic curve of 0.96, suggesting its potential as a reliable tool for detecting occult metastases during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photoacoustic Molecular Imaging for the Identification of Lymph Node Metastasis in Head and Neck Cancer Using an Anti-EGFR Antibody-Dye Conjugate. Nishio, N., van den Berg, NS., Martin, BA., et al.[2023]

In a phase I study involving 19 patients with advanced squamous cell carcinoma of the head and neck, the combination of panitumumab, carboplatin, and escalating doses of paclitaxel with intensity-modulated radiotherapy (IMRT) showed a high overall complete clinical response rate of 95%.

The treatment was generally well tolerated, with the maximum tolerated dose of paclitaxel identified at 30 mg/m², although all patients experienced significant side effects like mucositis and oral pain, indicating the need for careful management of these toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-finding study of paclitaxel with panitumumab, carboplatin and intensity-modulated radiotherapy in patients with locally advanced squamous cell cancer of the head and neck. Wirth, LJ., Allen, AM., Posner, MR., et al.[2020]

Panitumumab-IRDye800 has been developed as an effective intraoperative optical imaging agent for detecting EGFR-expressing tumors, showing high specificity and sensitivity in various mouse models with different levels of EGFR expression.

The study demonstrated a strong correlation between the level of EGFR expression in tumors and the uptake of the panitumumab-IRDye800, indicating its potential for precise tumor visualization during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and biological evaluation of panitumumab-IRDye800 conjugate as a fluorescence imaging probe for EGFR-expressing cancers. Bhattacharyya, S., Patel, N., Wei, L., et al.[2020]

The study evaluated the safety and stability of panitumumab-IRDye800CW, a near-infrared fluorescent dye conjugated to an approved therapeutic antibody, in 81 cancer patients over a 4.5-year period, finding a low adverse event rate of 7.4%, similar to that of panitumumab alone.

The conjugate demonstrated stability and safety for up to 54 months, supporting the potential for using therapeutic antibodies as diagnostic imaging agents with minimal additional toxicity concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Stability of Antibody-Dye Conjugate in Optical Molecular Imaging. Pei, J., Juniper, G., van den Berg, NS., et al.[2022]

In a pilot study involving seven patients with squamous cell tumors, radiolabeled antibodies targeting carcino-embryonic antigen (CEA) successfully identified all five primary tumors and two out of three secondary tumors, demonstrating effective imaging capabilities.

The study showed no false positive results and highlighted that serum or tissue CEA levels did not consistently correlate with imaging success, suggesting the potential for further research into more specific tumor antigens and imaging techniques for head and neck cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Head and neck cancer localization with indium labelled carcinoembryonic antigen: a pilot project. Timon, CI., McShane, D., Hamilton, D., et al.[2016]

A study using a fluorescently-labeled tumor-targeting agent, panitumumab-IRDye800CW, showed that it significantly enhances the identification of metastatic lymph nodes (LNs) in head and neck cancer patients during surgery.

This molecular imaging technique allows for a more focused evaluation of LNs, potentially improving prognostic accuracy compared to traditional methods of neck dissection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optical molecular imaging can differentiate metastatic from benign lymph nodes in head and neck cancer. Nishio, N., van den Berg, NS., van Keulen, S., et al.[2022]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Safety of panitumumab-IRDye800CW and cetuximab-IRDye800CW for fluorescence-guided surgical navigation in head and neck cancers. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Optimal Dosing Strategy for Fluorescence-Guided Surgery with Panitumumab-IRDye800CW in Head and Neck Cancer. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Photoacoustic Molecular Imaging for the Identification of Lymph Node Metastasis in Head and Neck Cancer Using an Anti-EGFR Antibody-Dye Conjugate. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Phase I dose-finding study of paclitaxel with panitumumab, carboplatin and intensity-modulated radiotherapy in patients with locally advanced squamous cell cancer of the head and neck. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Synthesis and biological evaluation of panitumumab-IRDye800 conjugate as a fluorescence imaging probe for EGFR-expressing cancers. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Safety and Stability of Antibody-Dye Conjugate in Optical Molecular Imaging. [2022]

7. Canada pubmed.ncbi.nlm.nih.gov

Head and neck cancer localization with indium labelled carcinoembryonic antigen: a pilot project. [2016]

8. England pubmed.ncbi.nlm.nih.gov

Optical molecular imaging can differentiate metastatic from benign lymph nodes in head and neck cancer. [2022]