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

Study Overview
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Brief Summary
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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.

Detailed Description
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Subjects who provide voluntary written informed consent, or have it provided by their legally acceptable representative, will be screened for eligibility. Subjects meeting all of the inclusion and none of the exclusion criteria will be eligible to participate. Surgical excision will occur at least 1 hour and no more than 36 hours after tozuleristide administration. Surgery will be performed by a neurosurgeon and the Canvas will be operated by a designated Imaging Operator. Fluorescence of tumor and ambiguous tissue during surgery will be assessed and scored. Biopsy samples of these tumor and ambiguous tissues will be collected for pathology analysis. All subjects will be monitored for safety during their participation in the study.

Official Title
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A Randomized, Blinded Study of Fluorescence Detection of Pediatric Primary Central Nervous System Tumors in Subjects Receiving Tozuleristide and Imaged With the Canvas System

Conditions
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Pediatric Central Nervous System Tumor

Intervention / Treatment
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* Drug: tozuleristide
* Device: Canvas System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1 (no tozuleristide)<br>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<br>* All subjects enrolled in the study will have their tissue imaged with the Canvas System.<br>* Other names: mSIRIS;|
| Experimental: Arm 2 (tozuleristide treated)<br>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<br>* Tozuleristide will be administered at least 1 hour and no more than 36 hours prior to planned surgical excision of their tumor.<br>* Other names: Tumor Paint;Device: Canvas System<br>* All subjects enrolled in the study will have their tissue imaged with the Canvas System.<br>* Other names: mSIRIS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 assessments made by the surgeon and imaging operator. These measures will be compared to the sensitivity and specificity of surgical designation of equivocal tissue without fluorescence. | During surgery (which occurs at least 1 hour post tozuleristide administration) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety - number of patients with adverse events | Safety will be assessed by physical examination and measurement of vital signs and laboratory safety parameters. | AEs will be collected from day of randomization until Day 8. Subjects will be contacted monthly for up to 3 months post-surgery for safety assessments. | 
| Extent of resection | Extent of resection will be evaluated by the surgeon and by central review of post-operative magnetic resonance images (MRI). Extent of resection will be designated in the following categories: gross total resection (GTR; all tumor removed), near total resection (NTR; bulk of tumor removed), sub-total resection (STR; residual tumor present). | At completion of surgery and up to 72 hours post-surgery for MRI assessment. If additional MRIs are obtained within 3 months post-surgery, they will be submitted for central MRI review. | 
| Concentration of tozuleristide in the blood (pharmacokinetics) | Tozuleristide concentration in the blood will be analyzed by chemical means and these data will be used to calculate pharmacokinetic parameters. | Subjects in Arm 2 only will have blood samples collected at 2 time points: One within 30 minutes after tozuleristide administration and one between 30 minutes and 180 minutes after tozuleristide administration. | 
| Performance of the Canvas system | The surgeon and imaging operator will complete a survey to evaluate the usability of the Canvas during surgery | After completion of surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tumor Paint, tozuleristide, Canvas imaging system, BLZ-100, CNS tumor, brain cancer, pediatrics, fluorescence guided surgery