Panitumumab for Head and Neck Cancer

Overseen By Nicole Jones, Clinical Research Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Vanderbilt-Ingram Cancer Center

Must not be taking: Antiarrhythmics

Disqualifiers: Infusion reactions, Pulmonary fibrosis, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 21 days

18 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically Class IA and Class III antiarrhythmic agents, at least 30 days before participating. If you are on these medications, you would be ineligible for the trial.

What data supports the effectiveness of the drug Panitumumab IRDye 800 for head and neck cancer?

Research shows that Panitumumab, when used with other treatments like radiotherapy, may improve outcomes for patients with head and neck cancer by targeting the EGFR pathway, which is involved in cancer growth. ^{1 2 3 4 5}

Is panitumumab safe for use in humans?

Panitumumab, including its variant Panitumumab-IRDye800CW, has been shown to have minimal toxicities in human trials, with no severe adverse reactions reported. In a study, only one mild adverse event occurred with Panitumumab-IRDye800CW, and no significant heart-related issues were observed. ^{1 3 4 6 7}

What makes the drug Panitumumab IRDye 800 unique for head and neck cancer?

Panitumumab IRDye 800 is unique because it combines the cancer-targeting ability of panitumumab, a monoclonal antibody that targets the epidermal growth factor receptor (EGFR), with a fluorescent dye (IRDye 800) to potentially aid in fluorescence-guided surgery, helping surgeons better visualize and remove cancerous tissue. ^{1 3 4 5 7}

What is the purpose of this trial?

This study is exploring the use of Panitumumab in Head and Neck Cancer. Panitumumab is an approved drug named Vectibix and is used as an anti-cancer agent in other cancers such as colorectal cancer. It works by attaching to the cancer cell in a unique way that allows the drug to get into the cancer tissue. In addition to the Panitumumab, participants will also receive a Panitumumab-IRDye800 (Pan800) or a fluorescently labeled Panitumumab infusion. IRDye800 is an investigational dye that, when tested in the lab, helps various characteristics of human tissue show up better when using a special camera during surgery. Panitumumab-IRDye800 is a combination of the drug and the dye that attaches to cancer cells and appears to make them visible to the doctor when he or she uses the special camera during surgery. The goal of this study is to use a novel and possibly safer approach to identify an optimal dose for panitumumab to treat cancer patients by using a new light-based therapy. In this study, different drug levels will be analyzed using this approach to understand how much drug reaches the tumor at different administered doses, which may help us provide safer and/or more effective therapies in the future. The goal is to identify the correct amount or dose of a drug that is needed for effective cancer therapies. Often, clinical studies look at how much of the drug can be tolerated before patients become sick, rather than how much of the drug is required to be effective. IRDye800 is an investigational dye that, when tested in the lab, helps various characteristics of human tissue show up better when using a special camera during surgery. Panitumumab-IRDye800 is a combination of the drug and the dye that attaches to cancer cells and appears to make them visible to the doctor when he or she uses the special camera during surgery. This will help the surgeon with clinical margins during surgery and will may have a clearer way to differentiate between cancer and healthy tissue.

Research Team

Eben L Rosenthal, MD

Principal Investigator

Vanderbilt University/Ingram Cancer Center

Eligibility Criteria

This trial is for adults over 18 with head and neck squamous cell carcinoma planning to undergo surgery. Participants must have normal organ function, agree to use contraception if of childbearing potential, and not be pregnant or breastfeeding. Exclusions include severe allergies to certain antibodies, specific heart conditions, electrolyte imbalances that can't be corrected, active tuberculosis, lung fibrosis except certain types from radiation therapy.

Inclusion Criteria

I am scheduled for surgery to remove my cancer.

Willing to review and sign written informed consent

I am over 18 years old.

Exclusion Criteria

History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins

I am not taking specific heart rhythm medications that could interact with the trial drug.

Patients with a history of infusion reactions or allergic reactions to panitumumab

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one or two doses of Panitumumab and Panitumumab-IRDye800 to assess tumor drug concentration and imaging efficacy

Up to 21 days

Surgery

Intraoperative use of Panitumumab-IRDye800 to optimize surgical margins and identify malignant lymph nodes

Single surgical event

Follow-up

Participants are monitored for safety and effectiveness after treatment and surgery

Up to 30 days

Treatment Details

Interventions

• Panitumumab IRDye 800

Trial Overview The study tests Panitumumab-IRDye800 in patients with head and neck cancer during surgery. It combines the approved drug Panitumumab (Vectibix) with a fluorescent dye IRDye800 to make cancer cells visible using a special camera. The aim is to find the optimal dose that's effective for treating cancer without causing sickness.

Participant Groups

Group I: Cohort 2a - Cohort 2c Experimental Treatment 1 Intervention

These cohorts will receive one dose of Pan800 and and two doses of Panitumumab at a range of doses (varying of specific cohort).

Group II: Cohort 1a - Cohort 1c Experimental Treatment 1 Intervention

These cohorts will receive one dose each of Pan800 (50 mg) and Panitumumab at a range of doses (varying of specific cohort).

Who Is Running the Clinical Trial?

Vanderbilt-Ingram Cancer Center

Lead Sponsor

Trials

221

Recruited

64,400+

Findings from Research

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]

In a phase 2 trial involving 152 patients with locally advanced squamous-cell carcinoma of the head and neck, the combination of chemoradiotherapy showed better local-regional control at 2 years (61%) compared to radiotherapy plus panitumumab (51%).

The study found that while both treatment groups experienced significant adverse events, the rates of serious adverse events were similar, suggesting that panitumumab does not provide a sufficient benefit to replace cisplatin in this treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab plus radiotherapy versus chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-2): a randomised, controlled, open-label phase 2 trial. Giralt, J., Trigo, J., Nuyts, S., et al.[2022]

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]

In a dummy run of the phase III trial involving 23 datasets for head and neck cancer treatment, 87% of gross tumor volumes (GTVs) were deemed acceptable, but only 43.5% of planning target volumes (PTVs) met the required standards, highlighting variability in treatment planning.

The study found significant correlations between the acceptability of treatment contours and the ability to meet dose constraints for organs at risk, indicating that careful planning is crucial for effective and safe radiotherapy in complex cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality assurance for the EORTC 22071-26071 study: dummy run prospective analysis. Fairchild, A., Langendijk, JA., Nuyts, S., et al.[2019]

In a trial involving 46 patients with high-risk, resected head and neck squamous cell carcinoma, the combination of the monoclonal antibody panitumumab with cisplatin chemoradiotherapy showed a promising 2-year progression-free survival rate of 70%.

The treatment was found to be tolerable, with 32% of patients experiencing severe toxicities, indicating that while the regimen is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of post-operative radiotherapy with concurrent cisplatin plus panitumumab in patients with high-risk, resected head and neck cancer. Ferris, RL., Geiger, JL., Trivedi, S., et al.[2020]

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 phase 2 trial involving 150 patients with locally advanced squamous-cell carcinoma of the head and neck, the addition of panitumumab to chemoradiotherapy did not improve local-regional control compared to chemoradiotherapy alone, with control rates of 61% versus 68%, respectively.

Patients receiving panitumumab experienced higher rates of severe side effects, such as dysphagia and mucosal inflammation, indicating that the combination treatment may not be safer or more effective than standard therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1): a randomised, controlled, open-label phase 2 trial. Mesía, R., Henke, M., Fortin, A., et al.[2022]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

Panitumumab plus radiotherapy versus chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-2): a randomised, controlled, open-label phase 2 trial. [2022]

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

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

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

Quality assurance for the EORTC 22071-26071 study: dummy run prospective analysis. [2019]

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

Phase II trial of post-operative radiotherapy with concurrent cisplatin plus panitumumab in patients with high-risk, resected head and neck cancer. [2020]

6. Australia pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1): a randomised, controlled, open-label phase 2 trial. [2022]