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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging agent called tozuleristide, which helps surgeons see oral cancer cells more clearly during surgery. Tozuleristide makes tumor cells glow under a special light, aiding doctors in distinguishing cancerous cells from healthy ones. Suitable candidates for this trial include those with suspected or confirmed oral cavity dysplasia or oral cavity squamous cell carcinoma, for whom surgery is recommended. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants the chance to contribute to groundbreaking advancements in cancer surgery.

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.

Is there any evidence suggesting that tozuleristide is likely to be safe for humans?

Research has shown that tozuleristide is generally safe for people. In earlier studies, no serious side effects were linked to tozuleristide. Even at doses of 9 mg and higher, no severe reactions prevented doctors from increasing the dose. This evidence suggests that tozuleristide is safe, which reassures those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for oral cancer, which typically involve surgery, radiation, and chemotherapy, tozuleristide offers a unique approach by acting as an imaging agent. This compound is infused into the body and helps illuminate cancer cells during surgery using near infrared (NIR) imaging. Researchers are excited about tozuleristide because it could possibly allow surgeons to more accurately identify and remove cancerous tissues, potentially leading to better surgical outcomes and fewer errors.

What evidence suggests that tozuleristide is effective for imaging oral cancer?

Research has shown that tozuleristide, which participants in this trial will receive, helps surgeons see cancer cells during surgery. In studies, tozuleristide accurately identified cancer cells, with a sensitivity of 95% and a specificity of 91% for head and neck cancer. This means it detected cancer cells in most cases and rarely gave false alarms. By making cancer cells glow under a special light, tozuleristide aids doctors in removing more cancer while preserving healthy tissue. ^{1 3 6 7 8}

Who Is on the Research Team?

Emily Marchiano

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26892902/

Fluorescence Identification of Head and Neck Squamous Cell ... Objective: To evaluate BLZ-100 uptake in models of HNSCC and oral dysplasia. Design, setting, and participants: This was an observational study (including ...

2. jamanetwork.com jamanetwork.com/journals/jamaotolaryngology/fullarticle/2492619

BLZ-100 and Identification of HNSCC and High-Risk Oral ... This study uses an orthotopic xenograft mouse model to examine BLZ-100 uptake in human HNSCC tumor xenografts and determine the sensitivity and.

3. sciencedirect.com sciencedirect.com/org/science/article/pii/S176528392300062X

Application of indocyanine green in the management ... Indocyanine green-assisted sentinel lymph node biopsy helps determine clean tumor boundaries, helps surgeons remove primary tumors completely.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4972605/

Fluorescence Identification of Head and Neck Squamous Cell ... A ROC curve based on this data demonstrated an AUC of 0.971, and a SBR of 2.5 corresponded to a 95% sensitivity and 91% specificity (Figure 2C). ROC coordinates ...

5. researchgate.net researchgate.net/publication/353712251_A_first-in-human_study_of_BLZ-100_tozuleristide_demonstrates_tolerability_and_safety_in_skin_cancer_patients

(PDF) A first-in-human study of BLZ-100 (tozuleristide ... For intermediate dose-levels (3–12 mg), 4 of 5 basal cell carcinomas and 4 of 4 melanomas were considered positive for BLZ-100 fluorescence. BLZ ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31069381/

Phase 1 Safety, Pharmacokinetics, and Fluorescence ... No dose-limiting toxicity was observed, and no reported adverse events were considered related to tozuleristide. At doses of 9 mg and above, the ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8355837/

A first-in-human study of BLZ-100 (tozuleristide) demonstrates ... The purpose of this study was to assess the safety, tolerability, and pharmacokinetics of BLZ-100 and to explore the pharmacodynamics of ...

8. researchgate.net researchgate.net/publication/333002193_Phase_1_Safety_Pharmacokinetics_and_Fluorescence_Imaging_Study_of_Tozuleristide_BLZ-100_in_Adults_With_Newly_Diagnosed_or_Recurrent_Gliomas

Phase 1 Safety, Pharmacokinetics, and Fluorescence ... Results: A total of 17 subjects received doses between 3 and 30 mg. No dose-limiting toxicity was observed, and no reported adverse events were ...