Study of Tozuleristide and the Canvas Imaging System in Pediatric Subjects With CNS Tumors Undergoing Surgery

NCT03579602 | Completed Phase 2 Results DMC FDA Drug FDA Device

• 2 other identifiers: BB-006PNOC012
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 9

Brief Summary

Many types of cancer are primarily treated with surgery and patient survival is directly related to the extent to which the tumor is able to be removed. It is often difficult for surgeons to distinguish tumor tissue from normal tissue or to detect tumor cells that have spread from the original tumor site, resulting in incomplete removal of the tumor and reduced patient survival. In some sites, such as the brain, it is critical to avoid damage to normal tissue around the tumor to prevent adverse effects of surgery on function. Tozuleristide is a drug that is thought to attach to tumor tissue and then fluoresces (glows) when a special light from the Canvas is shined on it. It is hypothesized that tozuleristide, when imaged with the Canvas, will improve surgical outcomes by allowing surgeons to visualize the edges of the tumor or other ambiguous tissue in real-time as they operate. The purpose of this study is to evaluate how well tozuleristide imaged with Canvas work at helping to distinguish between tumor and normal tissue during surgery in pediatric primary central nervous system tumors.

Conditions

Pediatric Central Nervous System Tumor

Keywords

Tumor Paint; tozuleristide; Canvas imaging system; BLZ-100; CNS tumor; brain cancer; pediatrics; fluorescence guided surgery

Outcome Measures

Primary Outcomes (3)

• Sensitivity and Specificity of Tozuleristide Fluorescence to Detect Tumor in Equivocal (Ambiguous) Tissue During Surgery When Imaged With the Canvas System

  Sensitivity and specificity of tozuleristide imaged with the Canvas system to fluorescently identify tumor in equivocal tissue will be evaluated based on central pathology consensus assessment of tumor and by imaging operator fluorescence assessment. These measures will be compared to the sensitivity and specificity of surgical designation of tumor (more likely tumor or less likely tumor) under white light. Sensitivity reflects the probability that tumor tissue evaluated is fluorescent. Specificity reflects the probability that normal tissue evaluated is not fluorescent. Equivocal tissues are those that the surgeon considers abnormal but ambiguous as tumor vs. not tumor under normal (white light) conditions.

  During surgery (which occurs at least 1 hour post tozuleristide administration)

• Ratio of Tozuleristide Sensitivity Compared to Surgeon Sensitivity

  Tozuleristide sensitivity as assessed by imaging operator fluorescence assessment compared to sensitivity of surgeon designation of tumor under white light in equivocal tissue biopsies. Sensitivity reflects the probability that tumor tissue evaluated is fluorescent. Equivocal tissues are those that the surgeon considers abnormal but ambiguous as tumor vs. not tumor under normal (white light) conditions.

  During surgery (which occurs at least 1 hour post tozuleristide administration)

• Ratio of Tozuleristide Specificity Compared to Surgeon Specificity

  Tozuleristide specificity as assessed by imaging operator fluorescence assessment compared to specificity of surgeon designation of tumor under white light in equivocal tissue biopsies. Specificity reflects the probability that normal tissue evaluated is not fluorescent. Equivocal tissues are those that the surgeon considers abnormal but ambiguous as tumor vs. not tumor under normal (white light) conditions.

  During surgery (which occurs at least 1 hour post tozuleristide administration)

Study Arms (2)

Arm 1 (no tozuleristide)

ACTIVE COMPARATOR

Subjects randomized to Arm 1 (\~9% of subjects) will not receive tozuleristide but will undergo standard of care neurosurgery and will have imaging performed with the Canvas System.

Device: Canvas System

Arm 2 (tozuleristide treated)

EXPERIMENTAL

Subjects randomized to Arm 2 (\~ 91% of subjects) will be administered tozuleristide at a dose of 15 mg/m\^2 at least 1 hour and no more than 36 hours prior to surgery. They will undergo standard of care neurosurgery and will have imaging performed with the Canvas System.

Drug: tozuleristide; Device: Canvas System

Interventions

tozuleristide DRUG

Tozuleristide will be administered at least 1 hour and no more than 36 hours prior to planned surgical excision of their tumor.

Also known as: BLZ-100, Tumor Paint

Arm 2 (tozuleristide treated)

Canvas System DEVICE

All subjects enrolled in the study will have their tissue imaged with the Canvas System.

Also known as: mSIRIS

Arm 1 (no tozuleristide); Arm 2 (tozuleristide treated)

Eligibility Criteria

• Age: 1 Month - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subjects must be \>1 month and ≤30 years of age at the time of study enrollment
• Subjects must have MRI obtained within 30 days of study enrollment documenting a measurable lesion consistent with a pediatric primary CNS tumor for which maximal safe resection is indicated
• Adequate renal function
• Adequate liver function
• Prior therapy: Subjects with prior therapy are eligible provided they have recovered from any acute toxic effects of prior therapy and have sufficient time interval prior to enrollment:
• Radiation therapy: subjects may not have had radiation therapy to the area of tumor planned to be resected within 28 days of study enrollment
• Chemotherapy: at least 14 days from any myelosuppressive chemotherapy (28 days if prior nitrosourea) and if prior chemotherapy, must have an absolute neutrophil count recovery of ≥ 1000/mm3 following count nadir
• Biologic: at least 7 days from any anti-neoplastic biologic agent (at least 3 half-lives since last administration of monoclonal antibodies)
• Immunotherapy: at least 42 days after completion of any cellular immunotherapy, such as CAR-T cell therapy
• Prior surgery for CNS tumors is allowed
• Prior tozuleristide: at least 1 week after prior dose of tozuleristide if previously treated
• Written informed consent must be obtained from the subject or parent or legal guardian prior to the conduct of study activities. Routine clinical tests, e.g., MRI, clinical laboratory studies, may be used for screening requirements. Assent, when appropriate, will be obtained according to institutional guidelines.
• The risks of treatment with tozuleristide during pregnancy have not been evaluated. Female subjects of child-bearing potential must agree not to attempt to become pregnant or undergo in vitro fertilization and, if participating in sexual activity that could lead to pregnancy, must use 2 reliable methods of contraception simultaneously for 30 days after surgery. Male subjects must agree not to attempt to father a child and, if participating in sexual activity that could lead to pregnancy, must use 2 reliable methods of contraception simultaneously for 30 days after surgery if their partner is of child-bearing potential.

You may not qualify if:

• Pregnancy and contraception: Subjects who are pregnant or breast-feeding or planning to conceive a child within 30 days are not eligible. Males and females of childbearing potential must agree to use 2 effective forms of contraception from the time of enrollment until 30 days post-surgery
• Subjects with on-going serious medical conditions (poorly controlled asthma, diabetes, heart disease) such that participation in the study could put the subject at increased risk of worsening their condition
• Subjects planned to undergo only a diagnostic biopsy procedure, without intent to resect tissue for therapeutic purposes (e.g., stereotactic pontine biopsy)
• Subjects who in the opinion of the investigator are not willing or able to comply with randomization procedures or other study-required study procedures and observations. Subjects previously enrolled and randomized to Arm 1 (control) are not eligible for re-enrollment unless a second surgery is required by standard of care.

Sponsors & Collaborators

• Blaze Bioscience Inc.: lead
• Pacific Pediatric Neuro-Oncology Consortium: collaborator

Study Sites (9)

Chlidren's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

University of Florida Shands Hospital

Gainesville, Florida, 32608, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Children's Minnesota

Saint Paul, Minnesota, 55102, United States

Location

Washington University St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Brain Neoplasms

Interventions

tozuleristide

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Brain Diseases; Central Nervous System Diseases

Results Point of Contact

• Title: Dr. Kristi Harrington
• Organization: Blaze Bioscience

Clinical.trials@blazebioscience.com

206-535-8144

Study Officials

• Sarah Leary, MD

  Seattle Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Central Pathology assessment and Central Radiology post-operative MRI assessment will be blinded to study arm and fluorescence data. Central Fluorescence assessment will be blinded to study arm.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: Subjects will be randomized 1:10 to 1 of 2 study arms. Subjects in arm 1 (\~9% of subjects) will not receive tozuleristide but will undergo neurosurgery and imaging will be performed with the Canvas. Subjects in arm 2 (\~91% of subjects) will receive tozuleristide and will undergo neurosurgery and imaging will be performed with the Canvas.

Study Record Dates

• First Submitted: June 15, 2018
• First Posted: July 6, 2018
• Study Start: November 26, 2018
• Primary Completion: April 1, 2022
• Study Completion: June 13, 2022
• Last Updated: June 27, 2024
• Results First Posted: June 27, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)