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

• ClinicalTrials.gov Identifier: NCT03579602
• Recruitment Status: Recruiting
• First Posted: July 6, 2018
• Last Update Posted: January 27, 2020
• Sponsor: Blaze Bioscience Inc.
• Collaborator: Pacific Pediatric Neuro-Oncology Consortium
• Information provided by (Responsible Party): Blaze Bioscience Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Pediatric Central Nervous System Tumor	Drug: tozuleristide; Device: Canvas System	Phase 2; Phase 3

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 114 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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 (Outcomes Assessor)
• Masking Description: Pathology assessment and post-operative MRI assessment will be blinded to fluorescence data.
• Primary Purpose: Other
• Official Title: A Randomized, Blinded Study of Fluorescence Detection of Pediatric Primary Central Nervous System Tumors in Subjects Receiving Tozuleristide and Imaged With the Canvas System
• Actual Study Start Date: November 26, 2018
• Estimated Primary Completion Date: August 2020
• Estimated Study Completion Date: November 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Arm 1 (no tozuleristide); 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; All subjects enrolled in the study will have their tissue imaged with the Canvas System.; Other Name: mSIRIS
Experimental: Arm 2 (tozuleristide treated); 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; Tozuleristide will be administered at least 1 hour and no more than 36 hours prior to planned surgical excision of their tumor.; Other Names: BLZ-100; Tumor Paint; Device: Canvas System; All subjects enrolled in the study will have their tissue imaged with the Canvas System.; Other Name: mSIRIS

Outcome Measures

Primary Outcome Measures :

1. Sensitivity and specificity of tozuleristide fluorescence to detect tumor in equivocal (ambiguous) tissue during surgery when imaged with the Canvas system [ Time Frame: During surgery (which occurs at least 1 hour post tozuleristide administration) ]
   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.

Secondary Outcome Measures :

1. Safety - number of patients with adverse events [ Time Frame: 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. ]
   Safety will be assessed by physical examination and measurement of vital signs and laboratory safety parameters.
2. Extent of resection [ Time Frame: 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. ]
   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).
3. Concentration of tozuleristide in the blood (pharmacokinetics) [ Time Frame: 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. ]
   Tozuleristide concentration in the blood will be analyzed by chemical means and these data will be used to calculate pharmacokinetic parameters.
4. Performance of the Canvas system [ Time Frame: After completion of surgery ]
   The surgeon and imaging operator will complete a survey to evaluate the usability of the Canvas during surgery

Eligibility Criteria

• Ages Eligible for Study: 1 Month to 30 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Subjects must be >1 month and ≤30 years of age at the time of study enrollment
2. 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
3. Adequate renal function
4. Adequate liver function

5. 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:

   1. Radiation therapy: subjects may not have had radiation therapy to the area of tumor planned to be resected within 28 days of study enrollment
   2. 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
   3. Biologic: at least 7 days from any anti-neoplastic biologic agent (at least 3 half-lives since last administration of monoclonal antibodies)
   4. Immunotherapy: at least 42 days after completion of any cellular immunotherapy, such as CAR-T cell therapy
   5. Prior surgery for CNS tumors is allowed
   6. Prior tozuleristide: at least 1 week after prior dose of tozuleristide if previously treated
6. 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.
7. 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:

1. 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
2. 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
3. Subjects planned to undergo only a diagnostic biopsy procedure, without intent to resect tissue for therapeutic purposes (e.g., stereotactic pontine biopsy)
4. 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.

Contacts and Locations

Contacts

Contact: PNOC Regulatory; (415) 502-1600; PNOC_Regulatory@ucsf.edu

Locations

United States, California

Chlidren's Hospital Los Angeles; Recruiting

Los Angeles, California, United States, 90027

Contact: Shaden Daas 323-361-3031 sdaas@chla.usc.edu

Principal Investigator: Ashley Margol, MD

University of California, San Francisco; Recruiting

San Francisco, California, United States, 94158

Contact: Sabine Mueller, MD, PhD 415-476-3831 sabine.mueller@ucsf.edu

Contact: Cassie Kline, MD cassie.kline@ucsf.edu

Principal Investigator: Sabine Mueller, MD, PhD

Sub-Investigator: Cassie Kline, MD

United States, District of Columbia

Children's National Medical Center; Recruiting

Washington, District of Columbia, United States, 20010

Contact: Lindsay Kilburn, MD lkilburn@childrensnational.org

Contact: Sabrina Malik samalik@childrensnational.org

Principal Investigator: Lindsay Kilburn, MD

United States, Florida

University of Florida Shands Hospital; Recruiting

Gainesville, Florida, United States, 32608

Contact: Jennifer F King jennifer.king@neurosurgery.ufl.edu

Principal Investigator: Lance S. Governale, MD

United States, Maryland

Johns Hopkins University; Recruiting

Baltimore, Maryland, United States, 21287

Contact: Kenneth J. Cohen, MD, MBA kcohen@jhmi.edu

Contact: Kenneth Seidl 410-502-8898 kseidl4@jhu.edu

Principal Investigator: Kenneth J. Cohen, MD, MBA

United States, Minnesota

Children's Minnesota; Recruiting

Saint Paul, Minnesota, United States, 55102

Contact: Anne E. Bendel, MD 612-813-5940 anne.bendel@childrensmn.org

Contact: Mary M. Skrypek, MD 612-813-7167 Maggie.Skrypek@childrensmn.org

Principal Investigator: Anne Bendel, MD

United States, Missouri

Washington University St. Louis Children's Hospital; Recruiting

Saint Louis, Missouri, United States, 63110

Contact: Karen Gauvain, MD gauvaink@wustl.edu

Contact: Nichole Jones nicholej@wustl.edu

Principal Investigator: Karen Gauvain, MD

United States, Washington

Seattle Children's Hospital; Recruiting

Seattle, Washington, United States, 98105

Contact: CBDC Intake CBDCintake@seattlechildrens.org

Principal Investigator: Sarah Leary, MD

Sponsors and Collaborators

Blaze Bioscience Inc.

Pacific Pediatric Neuro-Oncology Consortium

Investigators

• Principal Investigator: Sarah Leary, MD; Seattle Children's Hospital

More Information

• Responsible Party: Blaze Bioscience Inc.
• ClinicalTrials.gov Identifier: NCT03579602
• Other Study ID Numbers: BB-006; PNOC012 ( Other Identifier: Pacific Pediatric Neuro-Oncology Consortium )
• First Posted: July 6, 2018
• Last Update Posted: January 27, 2020
• Last Verified: January 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Blaze Bioscience Inc.:

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

Additional relevant MeSH terms:

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