Tozuleristide Imaging Agent for Oral Cancer

Overseen By Emily Marchiano

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Washington

Must not be taking: Photosensitizing medications

Disqualifiers: Pregnancy, Breastfeeding, Renal impairment, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

15 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take any medications that could cause fluorescence or a photochemical reaction, as these could interfere with the study results.

What data supports the effectiveness of the drug Tozuleristide for oral cancer?

Research shows that chlorotoxin, a component of Tozuleristide, has been effective in targeting and imaging brain tumors, suggesting its potential to help visualize tumors during surgery. Additionally, indocyanine green, another component, has been used in imaging for head and neck cancers, indicating its usefulness in detecting cancerous tissues. ^{1 2 3 4 5}

How does the drug Tozuleristide differ from other treatments for oral cancer?

Tozuleristide is unique because it is a near-infrared fluorescence (NIRF) imaging agent that helps surgeons visualize oral cancer during surgery, potentially improving the precision of tumor removal. This is different from standard treatments that do not typically involve real-time imaging to guide surgical procedures. ^{1 2 5 6 7}

What is the purpose of this trial?

This phase I/II trial studies the side effects of tozuleristide in imaging oral cavity squamous cell cancer and high-grade oral cavity dysplasia during surgery. Tozuleristide is an imaging agent that specifically binds to tumor cells. When exposed to near-infrared light, tozuleristide causes tumor cells to fluoresce (light up), so that surgeons may better distinguish tumor cells from healthy cells during surgery.

Research Team

Emily Marchiano

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for adults over 18 with suspected or confirmed oral cavity dysplasia or early to advanced squamous cell carcinoma needing surgery. Participants must be able to follow the study plan and use two reliable contraception methods if of child-bearing potential. Excluded are those on certain medications, pregnant or breastfeeding women, and individuals with specific sensitivities or abnormal blood tests.

Inclusion Criteria

I am suspected or confirmed to have early-stage mouth cancer needing surgery.

Able to provide written informed consent

I can attend all study visits and follow the study rules.

Exclusion Criteria

My kidney function is reduced with a creatinine clearance below 60 mL/min.

Enrolled in any other ongoing study

Known or suspected sensitivity to indocyanine green

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tozuleristide intravenously 1 hour before surgery, followed by surgical resection and near infrared imaging

1 day

1 visit (in-person)

Follow-up

Participants are monitored for adverse events and the effectiveness of tumor excision

7-21 days

Long-term follow-up

Participants are monitored for the accuracy of tozuleristide imaging in achieving negative margins and detecting tumors

Up to 12 months

Treatment Details

Interventions

• Tozuleristide

Trial Overview The trial is testing Tozuleristide, a fluorescent marker that binds to tumor cells making them glow under near-infrared light during surgery. This helps surgeons see and remove cancerous tissue more accurately compared to healthy tissue.

Participant Groups

Group I: Diagnostic (tozuleristide, surgery, NIR imaging) Experimental Treatment 3 Interventions

Beginning 1 hour before surgery, patients receive tozuleristide intravenously (IV) over 1-5 minutes. Patients then surgical resection per standard of care and undergo near infrared (NIR) imaging with standard of care device.

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Blaze Bioscience Inc.

Industry Sponsor

Trials

8

Recruited

250+

Findings from Research

IRDye 800CW chlorotoxin (CLTX) effectively targets brain tumor tissue in a mouse model of medulloblastoma, enhancing the visualization of tumor margins during surgery.

The study found that tumors can alter the blood-brain barrier's permeability, suggesting that larger imaging agents could be reconsidered for detecting tumors and aiding in surgical resection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of IRDye 800CW chlorotoxin as a targeting agent for brain tumors. Kovar, JL., Curtis, E., Othman, SF., et al.[2017]

DZ-1, a novel NIRF dye, shows significantly stronger fluorescence intensity and better tumor targeting capabilities compared to the FDA-approved dye ICG, making it a promising tool for noninvasive tumor imaging.

In preclinical models, DZ-1 effectively accumulates in tumor tissue and specifically targets hepatocellular carcinoma (HCC), demonstrating potential for both imaging and therapeutic applications, especially when conjugated with gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Application of Heptamethine Cyanine Dye DZ-1 and Indocyanine Green for Imaging and Targeting in Xenograft Models of Hepatocellular Carcinoma. Zhang, C., Zhao, Y., Zhang, H., et al.[2018]

Chlorotoxin (CTX) has been identified as an effective targeting ligand for glioma, allowing nanoparticles (NPs) to specifically bind to these tumors for improved imaging and therapy.

CTX-conjugated nanoparticles can be used not only for targeted magnetic resonance and fluorescence imaging but also as carriers for anticancer drugs or therapeutic genes, enhancing the effectiveness of chemotherapy and gene therapy for glioma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chlorotoxin-conjugated nanoparticles for targeted imaging and therapy of glioma. Zhao, L., Shi, X., Zhao, J.[2019]

The synthesized meso-tetraphenylchlorin-chitosan nanoconjugates, with a diameter of 140-200 nm, effectively enhance plasmid DNA transfection in human colon carcinoma cells when activated by red light (650 nm), indicating their potential for photochemical internalization (PCI).

In preliminary in vivo studies with tumor-bearing mice, these nanoconjugates demonstrated strong photodynamic therapy (PDT) effects and enhanced the efficacy of bleomycin treatment, suggesting their promising role in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endosome Targeting meso-Tetraphenylchlorin-Chitosan Nanoconjugates for Photochemical Internalization. Gaware, VS., Håkerud, M., Juzeniene, A., et al.[2017]

The study demonstrated that cetuximab conjugated to indocyanine green (ICG) effectively illuminated head and neck tumors in mice, showing strong fluorescence 24 hours post-injection, which correlated with the dose administered.

While the imaging showed high specificity (96%) and moderate sensitivity (78.4%) for detecting residual disease after surgery, the overall sensitivity was not sufficient for clinical application, indicating the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of indocyanine green-labeled cetuximab to detect xenografted head and neck cancer cell lines. Withrow, KP., Gleysteen, JP., Safavy, A., et al.[2015]

Photodynamic therapy (PDT) using benzoporphyrin derivative (BPD) shows promise in treating oral cancer, and combining it with indocyanine green (ICG) for photoacoustic imaging (PAI) does not significantly affect BPD's efficacy in two oral cancer cell lines.

While the combination of BPD and ICG can enhance PAI-guided PDT, researchers must be cautious of ICG's photodegradation when used alongside BPD, which could impact treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mutual impact of clinically translatable near-infrared dyes on photoacoustic image contrast and in vitro photodynamic therapy efficacy. Petrovic, LZ., Xavierselvan, M., Kuriakose, M., et al.[2021]

WST11, a novel compound for vascular-targeted photodynamic therapy, shows rapid clearance from circulation in mice (1.65 min) and rats (7.5 min), indicating a quick systemic elimination which is important for minimizing side effects.

In treating M2R melanoma xenografts, WST11-VTP resulted in 100% tumor flattening and a 70% cure rate at a dose of 9 mg/kg, demonstrating its efficacy as a therapeutic agent in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

WST11, a novel water-soluble bacteriochlorophyll derivative; cellular uptake, pharmacokinetics, biodistribution and vascular-targeted photodynamic activity using melanoma tumors as a model. Mazor, O., Brandis, A., Plaks, V., et al.[2019]

References

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

Characterization of IRDye 800CW chlorotoxin as a targeting agent for brain tumors. [2017]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The Application of Heptamethine Cyanine Dye DZ-1 and Indocyanine Green for Imaging and Targeting in Xenograft Models of Hepatocellular Carcinoma. [2018]

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Chlorotoxin-conjugated nanoparticles for targeted imaging and therapy of glioma. [2019]

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

Endosome Targeting meso-Tetraphenylchlorin-Chitosan Nanoconjugates for Photochemical Internalization. [2017]

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

Assessment of indocyanine green-labeled cetuximab to detect xenografted head and neck cancer cell lines. [2015]

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

Mutual impact of clinically translatable near-infrared dyes on photoacoustic image contrast and in vitro photodynamic therapy efficacy. [2021]

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

WST11, a novel water-soluble bacteriochlorophyll derivative; cellular uptake, pharmacokinetics, biodistribution and vascular-targeted photodynamic activity using melanoma tumors as a model. [2019]