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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new imaging agent called Pegsitacianine (also known as ONM-100 or indocyanine green-labeled polymeric micelles) to help surgeons see head and neck cancers more clearly during surgery. The research aims to test Pegsitacianine's effectiveness in detecting primary tumors and their spread to lymph nodes. It seeks participants diagnosed with head and neck squamous cell carcinoma or those with unknown primary cancer in this area. Participants should have a confirmed diagnosis or a strong suspicion of cancer and be able to undergo surgery. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to potentially groundbreaking advancements in cancer surgery.

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 prior data suggests that Pegsitacianine is safe for imaging in head and neck cancer?

Research shows that pegsitacianine is an imaging agent linked to indocyanine green (ICG), which is widely used in medical imaging, particularly for spotting tumors. Studies have found that ICG-based systems help surgeons locate cancerous areas more easily and can lead to smaller surgical incisions.

Although specific safety data on pegsitacianine is limited, similar imaging agents have been successfully used to detect head and neck cancer, suggesting that the treatment might be well-tolerated. As this trial is in its second phase, earlier evidence may indicate its safety in humans. However, more research is needed to fully understand its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about pegsitacianine for head and neck cancers because it offers a new way to visualize tumors and metastatic lymph nodes using fluorescence imaging. Unlike traditional imaging methods, which rely on scans like CT or MRI, pegsitacianine lights up cancerous areas with a special dye, making it easier for surgeons to see and remove tumors. This innovative approach could potentially lead to more precise surgeries and better outcomes for patients, helping to ensure that more of the cancer is removed while sparing healthy tissue.

What evidence suggests that Pegsitacianine imaging is effective for head and neck cancer?

Research has shown that pegsitacianine is a promising tool for spotting head and neck cancers. In this trial, participants will receive a single dose of pegsitacianine to evaluate its diagnostic performance in detecting primary tumors and metastatic lymph nodes. Similar tools, such as ONM-100, have proven very effective, achieving a 100% success rate in identifying tumors and a 92% accuracy in confirming their cancerous nature during surgeries. Pegsitacianine is designed to make cancer cells glow, aiding surgeons in seeing and removing them more easily. This can improve the detection of main tumors and affected lymph nodes. Although direct data on pegsitacianine remains limited, its design and early results suggest it could enhance cancer detection. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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 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]

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 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]

Citations

1. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/coa.14263

The Use of Fluorescent Markers to Detect and Delineate ... ONM-100 demonstrated 100% sensitivity and 92% specificity when used during head and neck cancer resections in the oral cavity. ONM-100 was well ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12424049/

A Phase 2 Multicenter Clinical Trial of Intraoperative ... Pegsitacianine is one such pH-activatable tracer that has recently been developed. It consists of polymeric micelles labeled with indocyanine ...

3. withpower.com withpower.com/trial/phase-2-head-and-neck-cancer-2023-f4558

Pegsitacianine Imaging 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.

4. researchgate.net researchgate.net/publication/351827152_A_Standardized_Framework_for_Fluorescence-Guided_Margin_Assessment_for_Head_and_Neck_Cancer_Using_a_Tumor_Acidosis_Sensitive_Optical_Imaging_Agent

(PDF) A Standardized Framework for Fluorescence-Guided ... A Standardized Framework for Fluorescence-Guided Margin Assessment for Head and Neck Cancer Using a Tumor Acidosis Sensitive Optical Imaging Agent. May 2021 ...

5. sciencedirect.com sciencedirect.com/org/science/article/abs/pii/S2976871324000073

Indocyanine green within glycosylated polymeric micelles ... All the results presented in this work, indicate that ICG-loaded PMs can potentially be used as image probe agents for IGS, SLNB and breast ...

6. synapse.patsnap.com synapse.patsnap.com/drug/932e465aa1e94d9a8a87f6854f6a6c0d

Pegsitacianine - Drug Targets, Indications, Patents Pegsitacianine is a pH-sensitive polymeric micelle conjugated to the fluorophore indocyanine green. The micelle disassembles in acidic microenvironments, such ...

7. nature.com nature.com/articles/s41467-020-16814-4

Exploiting metabolic acidosis in solid cancers using a ... Briefly, ONM-100 consists of polymeric micelles labeled with IndoCyanine Green (ICG). Chemically, the ONM-100 drug substance comprises a ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0734975016300428

Indocyanine green delivery systems for tumour detection ... SLN biopsy using ICG fluorescence reduces time of surgery, and improves lymph node detection allowing a surgeon to make a minimal incision and prolonging high ...