Pegsitacianine Imaging for Head and Neck Cancer

Overseen By Baran Sumer, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Hepatotoxic drugs

Disqualifiers: Liver disease, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 1 week

120 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take medications with a high chance of liver damage during the study. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the treatment Pegsitacianine for head and neck cancer?

While there is no direct data on Pegsitacianine, similar imaging agents have shown promise in improving the detection and treatment of head and neck cancers. For example, nanoparticles used in imaging have helped identify cancerous tissues and improve surgical precision, which could suggest potential benefits for Pegsitacianine in similar applications. ^{1 2 3 4 5}

How does Pegsitacianine Imaging differ from other treatments for head and neck cancer?

Pegsitacianine Imaging is unique because it uses a near-infrared (NIR) fluorescence technique to help visualize tumors during surgery, which can improve the precision of tumor removal. This approach is different from traditional treatments that do not provide real-time imaging guidance during surgical procedures. ^{6 7 8 9 10}

What is the purpose of this trial?

This is a non-randomized, open-label, single-center, safety and imaging feasibility study of Pegsitacianine, an intraoperative fluorescence imaging agent.

Eligibility Criteria

Adults over 18 with certain types of head and neck cancers, including those without a known primary tumor location but with metastatic disease. Participants must have proper organ function, agree to use contraception, and avoid alcohol before the trial. Those very ill or unable to consent are excluded.

Inclusion Criteria

Biopsy-confirmed diagnosis, for primary or recurrent disease (or high clinical suspicion in the opinion of the Investigator)

Documented negative serum pregnancy test for women of childbearing potential

Adequate potential for follow up

Exclusion Criteria

Life expectancy <12 weeks

Alcohol consumption within 72 hours before Pegsitacianine administration

Lab values or any sign, symptom, or medical condition that in the opinion of the PI would prevent surgical resection

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Single dose of 1 mg/kg Pegsitacianine administered 6-100 hours prior to surgery for imaging primary tumors

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including vital signs, physical examination, and laboratory tests

10 days

Multiple visits (in-person and virtual)

Long-term monitoring

Participants are monitored for diagnostic performance and safety over a 5-year period

5 years

Treatment Details

Interventions

• Pegsitacianine

Trial Overview The study is testing Pegsitacianine as an imaging agent during surgery for cancer detection in patients with head and neck cancers. It's an open-label trial where all participants receive the agent to assess its safety and effectiveness in identifying cancerous tissue.

Participant Groups

Group I: Part 1 - Cohort A Active Control 1 Intervention

In Part 1 the single dose of 1 mg/kg of pegsitacianine given 6-300 hours prior to surgery will be used to image primary tumors in patients with HNSCC to evaluated to verify the diagnostic performance of pegsitacianine fluorescence imaging for detecting primary tumors and metastatic lymph nodes.

Group II: Part 2 - Cohort B Active Control 1 Intervention

In Part 2, pegsitacianine the single dose of 1 mg/kg of given 6-300 hours prior to surgery will be used to in patients with unknown primary cancer of the head and neck. These patients typically undergo exam under anesthesia with a laryngoscopy as well as panendoscopy for identifying the source of the metastatic cancer found in the cervical nodes. The diagnostic performance of pegsitacianine fluorescence imaging for detecting primary tumors and metastatic lymph nodes in these patients will be evaluated. All the available data to date will be used to decide the additional tumor type(s), number of patients per tumor type, and number of Group(s) to be enrolled.

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

64 Cu-porphysome nanoparticles provide enhanced imaging of cancerous tissues and lymph nodes in a rabbit model of head and neck cancer, allowing for better detection during positron emission tomography (PET) imaging.

These nanoparticles also enable real-time fluorescence visualization of tumors during surgery, helping surgeons accurately identify cancerous areas and preserve healthy tissue, which can improve surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodal Nanoparticle for Primary Tumor Delineation and Lymphatic Metastasis Mapping in a Head-and-Neck Cancer Rabbit Model. Muhanna, N., MacDonald, TD., Chan, H., et al.[2019]

The multimodal porphyrin lipoprotein-mimicking nanoparticle (PLP) significantly improves the accuracy of diagnosing head and neck cancer (HNC) by enabling precise detection of primary tumors and metastatic lymph nodes, as demonstrated in a rabbit model.

PLP-based photodynamic therapy (PDT) resulted in a remarkable increase in tumor cell apoptosis (73.2% vs. 7.1% with PLP alone) and successfully eradicated primary tumors without harming surrounding healthy tissues, indicating its potential for effective HNC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodal Image-Guided Surgical and Photodynamic Interventions in Head and Neck Cancer: From Primary Tumor to Metastatic Drainage. Muhanna, N., Cui, L., Chan, H., et al.[2016]

The study demonstrated that 100 nm theranostic nanoparticles can enhance radiation therapy for head and neck squamous cell carcinoma, showing reduced tumor growth and lung metastasis in rat models.

These nanoparticles provide both imaging capabilities and therapeutic benefits, allowing for better radiation therapy planning and improved treatment efficacy, as evidenced by their optimal tumor uptake and effectiveness in reducing tumor size.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

X-ray and MR Contrast Bearing Nanoparticles Enhance the Therapeutic Response of Image-Guided Radiation Therapy for Oral Cancer. Sharma, G., Razeghi Kondelaji, MH., Sharma, GP., et al.[2023]

The study developed a new imaging technique using dual-modal near-infrared II (NIR II) luminescence and T1 magnetic resonance imaging (MRI) that targets the cMet receptor, which is overexpressed in head and neck squamous cell carcinomas (HNSCCs).

This innovative approach allows for better visualization and accumulation of imaging agents in HNSCC tumors, potentially leading to more accurate and sensitive early detection of this common cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Met-Targeted Dual-Modal MRI/NIR II Imaging for Specific Recognition of Head and Neck Squamous Cell Carcinoma. Wu, J., Liu, J., Lin, B., et al.[2021]

Ultra-small NaYF4:Nd3+/NaGdF4 nanocrystals coated with manganese dioxide (usNP-MnO2) show promise for improving oxygen levels in head and neck squamous cell carcinomas (HNSCC) by modulating tumor hypoxia.

The study utilized dual modality imaging (MRI and photoacoustic imaging) to successfully visualize nanoparticle delivery and increased oxygen saturation in tumor models, indicating a potential method for selecting patients who could benefit from these hypoxia-modifying therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photoacoustic and Magnetic Resonance Imaging of Hybrid Manganese Dioxide-Coated Ultra-small NaGdF4 Nanoparticles for Spatiotemporal Modulation of Hypoxia in Head and Neck Cancer. Rich, LJ., Damasco, JA., Bulmahn, JC., et al.[2021]

The study found that 2% mTHPP-loaded micelles were the most effective for photodynamic therapy, achieving 100% cytotoxicity in head and neck cancer cells with minimal dark toxicity, making them a promising treatment option.

At 0.5% loading, the micelles showed the highest fluorescence intensity, while 2% loading maximized singlet oxygen generation, indicating that careful optimization of loading percentages is crucial for enhancing therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and optimization of mTHPP nanoparticles for photodynamic therapy of head and neck cancer. Ding, H., Mora, R., Gao, J., et al.[2011]

The study developed a lipophilic near-infrared (NIR) probe, DiR, incorporated into PEG-b-PCL micelles, which significantly improved the solubility of the probe in water and enhanced tumor visualization during surgery.

Both self-quenched and nonquenched states of DiR showed high tumor-to-muscle ratios (30-43), indicating that this imaging agent can effectively guide surgeons in the complete removal of solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo cancer imaging by poly(ethylene glycol)-b-poly(ɛ-caprolactone) micelles containing a near-infrared probe. Cho, H., Indig, GL., Weichert, J., et al.[2022]

Encapsulating indocyanine green (ICG) in polymeric micelles significantly enhances its stability and fluorescence, making it more effective for biological applications compared to free ICG.

The PEG-PLL-PLLeu-ICG micelles demonstrated high cellular uptake and excellent passive tumor targeting in vivo, suggesting their potential for use in tumor diagnosis, imaging, and photothermal therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hybrid polypeptide micelles loading indocyanine green for tumor imaging and photothermal effect study. Wu, L., Fang, S., Shi, S., et al.[2022]

The formulation of the osmium-based photosensitizer ML18J03 into micelles (Mic-ML18J03) significantly enhances its luminescence quantum yield, improving in vivo imaging capabilities by 100 times and providing 47-fold increased luminescence signals in tumors.

Mic-ML18J03 shows up to 11.7-fold tumor selectivity and enhances the production of reactive molecular species by 2-3 times, indicating its potential for more effective photodynamic therapy (PDT) with reduced quenching effects compared to the unformulated version.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enabling In Vivo Optical Imaging of an Osmium Photosensitizer by Micellar Formulation. Shah, D., Eroy, M., Fakhry, J., et al.[2023]

In a study using a breast cancer model with mice, small polymerized polydiacetylene (PDA) micelles coated with polyethylene glycol (PEG) showed a tumor uptake of nearly 3% of the injected dose, indicating effective passive targeting through the enhanced permeability and retention effect.

When loaded with the anticancer drug paclitaxel, the PDA-PEG2000 micelles were able to inhibit tumor growth, demonstrating their potential for both imaging and drug delivery in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-targeted polydiacetylene micelles for in vivo imaging and drug delivery. Mackiewicz, N., Gravel, E., Garofalakis, A., et al.[2018]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Multimodal Nanoparticle for Primary Tumor Delineation and Lymphatic Metastasis Mapping in a Head-and-Neck Cancer Rabbit Model. [2019]

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

Multimodal Image-Guided Surgical and Photodynamic Interventions in Head and Neck Cancer: From Primary Tumor to Metastatic Drainage. [2016]

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

X-ray and MR Contrast Bearing Nanoparticles Enhance the Therapeutic Response of Image-Guided Radiation Therapy for Oral Cancer. [2023]

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

Met-Targeted Dual-Modal MRI/NIR II Imaging for Specific Recognition of Head and Neck Squamous Cell Carcinoma. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Photoacoustic and Magnetic Resonance Imaging of Hybrid Manganese Dioxide-Coated Ultra-small NaGdF4 Nanoparticles for Spatiotemporal Modulation of Hypoxia in Head and Neck Cancer. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Characterization and optimization of mTHPP nanoparticles for photodynamic therapy of head and neck cancer. [2011]

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

In vivo cancer imaging by poly(ethylene glycol)-b-poly(ɛ-caprolactone) micelles containing a near-infrared probe. [2022]

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

Hybrid polypeptide micelles loading indocyanine green for tumor imaging and photothermal effect study. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Enabling In Vivo Optical Imaging of an Osmium Photosensitizer by Micellar Formulation. [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

Tumor-targeted polydiacetylene micelles for in vivo imaging and drug delivery. [2018]