A Fluorescent Tumor Marking Agent, Tozuleristide, for Imaging Oral Cavity Squamous Cell Cancer and High-Grade Oral Cavity Dysplasia During Surgery

Intraoperative Visualization of Oral Cavity Squamous Cell Carcinoma and High-Grade Dysplasia With Tozuleristide, a Fluorescent Tumor Marking Agent

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.

Study Overview

• Status: Recruiting
• Conditions: Stage III Lip and Oral Cavity Cancer AJCC v8; Oral Cavity Squamous Cell Carcinoma; Stage I Lip and Oral Cavity Cancer AJCC v8; Stage II Lip and Oral Cavity Cancer AJCC v8; Stage IVA Lip and Oral Cavity Cancer AJCC v8
• Intervention / Treatment: Procedure: Therapeutic Conventional Surgery; Procedure: Near Infrared Imaging; Drug: Tozuleristide

Detailed Description

OUTLINE:

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.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Rebecca Wood; Phone Number: 206-606-6970; Email: rwood1@fredhutch.org

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutch/University of Washington Cancer Consortium
      • Principal Investigator: Emily Marchiano
      • Contact: Rebecca Wood; Phone Number: 206-606-6970; Email: rwood1@fredhutch.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult subjects age >= 18 years (yr)
• Subjects must have suspected or confirmed oral cavity dysplasia or cT1-4 squamous cell carcinoma for which surgical excision is deemed clinically indicated by the treating physician. Histology confirmation not required prior to surgery
• Able to provide written informed consent
• If of child-bearing potential, agree to the continued use of 2 reliable forms of contraception from study enrollment through 30 days after receiving the study product. Male subjects must agree to use 2 reliable methods of contraception simultaneously for 30 days after receiving the study product if their partner is of child-bearing potential
• Available for all study visits and able to comply with all study requirements

Exclusion Criteria:

• Known or suspected sensitivity to indocyanine green
• In the opinion of the treating physician, subject has received photosensitizing medication that could interfere or confound study results
• Any current medications with the potential to generate fluorescence or photochemical reaction
• Enrolled in any other ongoing study
• Currently lactating or breastfeeding
• Positive pregnancy test or planning to become pregnant within 30 days (d) of receiving tozuleristide
• Any current condition, including psychological and social situations which, in the opinion of the investigator, would impact adversely on the subject or the interpretation of the study data
• Creatinine clearance < 60 mL/min
• Aspartate aminotransferase (AST) > 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) > 1.5 x ULN
• Bilirubin > 1.5 x ULN

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diagnostic (tozuleristide, surgery, NIR imaging); 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.	Procedure: Therapeutic Conventional Surgery; Undergo surgery; Procedure: Near Infrared Imaging; Undergo NIR imaging; Other Names: Near-Infrared Imaging; NIR Imaging; Drug: Tozuleristide; Given IV; Other Names: BLZ-100

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AEs)	Adverse events will be summarized as the number and percentage of patients with each type of adverse event, per Criteria for Adverse Events version 5.0.	7-21 days after drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects without tumor fluorescence after receiving tozuleristide		Up to 12 months
Sensitivity of tozuleristide fluorescence to detect tumor in tissue biopsies	Will be estimated by a repeated measure logistic regression modeling the probability of positive tumor. The model includes an exchangeable working correlation structure to account for potential correlations of biopsies within subject for the tumor-positive tissue biopsies. A general estimating equation (GEE) method will be used to estimate the regression parameters.	Up to 12 months
Specificity of tozuleristide fluorescence to detect tumor in tissue biopsies	Will be estimated by a repeated measure logistic regression modeling the probability of negative tumor. The model includes an exchangeable working correlation structure to account for potential correlations of biopsies within subject for the tumor-positive tissue biopsies. A GEE method will be used to estimate the regression parameters. The repeated measures logistic regression will model the probability of tumor-negative biopsies.	Up to 12 months
Positive predictive value of tozuleristide fluorescence to detect tumor in tissue biopsies		Up to 12 months
Negative predictive value of tozuleristide fluorescence to detect tumor in tissue biopsies		Up to 12 months
Achievement of negative margins in tozuleristide-guided oral cavity tumor excision	To investigate the accuracy of tozuleristide fluorescent imaging in identifying tumor and achieving negative margins during excision of oral cavity squamous cell carcinoma and high-grade dysplasia.	Up to 12 months

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Blaze Bioscience Inc.
• Investigators: Principal Investigator: Emily Marchiano, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Estimated): May 4, 2024
• Primary Completion (Estimated): January 20, 2026
• Study Completion (Estimated): January 20, 2027

Study Registration Dates

• First Submitted: March 17, 2022
• First Submitted That Met QC Criteria: March 30, 2022
• First Posted (Actual): April 7, 2022

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Lip Diseases; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Mouth Neoplasms; Lip Neoplasms
• Other Study ID Numbers: RG1122110; NCI-2022-01734 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); FHIRB0020096 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No