This clinical trial aims to determine if FG001 can assist surgeons in identifying the difference between tumor and healthy tissue during surgery in participants with newly diagnosed high-grade glioma. The scheduled neurosurgical tumor resection will occur under NIR fluorescence guidance and support the surgeons in achieving complete removal of the cancer. FG001 is a 'fluorescent imaging agent,' which is a dye that glows under a special light to help doctors see certain tissues. The main questions it aims to answer are: 1. To see how well a special light (called NIR fluorescence imaging) can show the difference between the tumor and the nearby healthy tissue during surgery. This difference is measured by comparing how bright the tumor looks to how bright the normal tissue looks. 2. Another goal is to find out how many patients have almost all the tumor removed. This is checked by looking at MRI scans, taken within 48 hours after surgery, to see if the leftover tumor is smaller than 0.175 cubic centimeters. Participants will receive FG001 before tumor resection surgery and will participate in follow-up visits during the six months after surgery. Follow-up visits may include brain MRI, bloodwork, physical assessments, vital signs, assessment of functional and neurologic status, quality-of-life assessments, adverse event monitoring, and review of concomitant medications.
INVESTIGATIONAL PLAN This is a prospective, multicenter, Phase 2 dose confirmation study of FG001 (0.45 mg/kg) with diagnostic purpose (optimal imaging agent) and a single group under NIR fluorescence imaging with FG001. Dosage will be 0.45 mg/kg FG001, single dose, intravenous injection, 12 to 19 hours before surgery. Neurosurgical tumor resection will be supported by NIR fluorescence imaging with FG001. Evaluation of MR imaging and histopathology will be conducted by central neuroradiologists and neuropathologists, respectively. Overall Design The overall trial design is an open-label assessment of FG001 to confirm the acceptability of the dose selected (0.45 mg/kg administered within 12-19 hours of surgery). Trial Schedule Eligible subjects will undergo the following sequence of events: * Screening (to be completed ≤30 days before surgery) * Pre-operative MRI (obtained within 48 hours) prior to surgery * Pretreatment (conducted in accordance with local institution practice) * Pre-dose Anti-drug antibody (ADA) sampling * Administration of FG001 12-19 hours prior to surgery * Pre-operative assessments (1 hour and 3-12 hours following IP administration) * Neurosurgical intervention with planned study assessments * Surgical Phase I: Dura View * Surgical Phase II: Cortex View * Surgical Phase III: Tumor View * Surgical Phase IV: Tumor Margin View * Surgical Phase V: Tumor Cavity View * Postoperative Assessments * Day 0 (±12 hours): Laboratory assessments, tumor characterization labs (including IDH and MGMT), and adverse events * Within 48 hours: MRI * Over 72 hours post-operative: collection of FG001 urine excretion metabolites * Over 48 hours post-operative: PK analysis * Day 3 (±12 hours): physical exam, vital signs, NANO scale, ECG and AEs * Post-operative Assessments: * Day 7 (±1 day): physical examination, safety assessments, Karnofsky Performance Status, Neurologic Assessment in Neuro-Oncology Scale, neurocognitive assessment, serum chemistries and hematology, anti-drug antibody sampling, ECG, adverse event monitoring, and concomitant medication review. * Week 6 (±1 week): follow-up assessments, including Karnofsky Performance Status, Neurologic Assessment in Neuro-Oncology Scale, neurocognitive assessment, quality-of-life assessment, adverse event monitoring, concomitant medication review, steroid use documentation, temozolomide compliance, and anti-drug antibody sampling. * 3 Months (±2 weeks): follow-up assessments, including MRI, Karnofsky Performance Status, Neurologic Assessment in Neuro-Oncology Scale, neurocognitive assessment, quality-of-life assessment, adverse event monitoring, concomitant medication review, temozolomide compliance, steroid use documentation, and disease progression and survival assessment. * 6 Months (±2 weeks): final follow-up assessments, including physical examination, vital signs, MRI, Karnofsky Performance Status, Neurologic Assessment in Neuro-Oncology Scale, neurocognitive assessment, quality-of-life assessment, adverse event monitoring, concomitant medication review, temozolomide compliance, steroid use documentation, and disease progression and survival assessment, as applicable.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
76
FG001 is an investigational optical imaging agent administered as a single intravenous dose prior to neurosurgical tumor resection to support intraoperative visualization of malignant tissue under near-infrared fluorescence guidance.
University of Miami
Miami, Florida, United States
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States
UPMC Presbyterian Hospital
Pittsburgh, Pennsylvania, United States
University of Texas Medical Branch
Galveston, Texas, United States
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, United States
Tumor-to-Background Ratio of Near-Infrared Fluorescence Imaging of Tumor Bulk In Situ and Adjacent Normal Tissue
Performance of a single dose of FG001 0.45 mg/kg administered 12 to 19 hours before surgery will be assessed using the tumor-to-background ratio of near-infrared fluorescence imaging of tumor bulk in situ and adjacent normal tissue under direct visualization. Tumor-to-background ratio will be calculated as the mean fluorescence intensity in the tumor region of interest divided by the mean fluorescence intensity in the background region of interest.
Time frame: Intraoperatively, 12 to 19 hours after FG001 administration
Proportion of Patients Achieving Gross Total Resection Based on Volumetric Analysis of Contrast-Enhanced MRI
Gross total resection will be defined as less than 0.175 cm³ residual contrast-enhancing tumor, as determined by volumetric analysis of contrast-enhanced MRI performed within 48 hours postoperatively.
Time frame: Within 48 hours postoperatively
Proportion of Subjects Achieving RANO Resect Class 1 Based on Early Postoperative MRI
RANO Resect Class 1, also referred to as supramaximal contrast-enhancing resection, will be assessed using early postoperative MRI. RANO Resect Class 1 is defined as complete contrast-enhancing tumor resection, with no measurable residual contrast-enhancing tumor volume, and residual non-contrast-enhancing T2/FLAIR volume of 5.0 cm³ or less.
Time frame: Within 48 hours postoperatively
Proportion of Subjects Achieving Response Assessment in Neuro-Oncology Resect Class 2 Based on Early Postoperative MRI
Response Assessment in Neuro-Oncology Resect Class 2, defined as complete or near-total resection of contrast-enhancing tumor, will be assessed using early postoperative MRI following fluorescence-guided surgery. Class 2A is defined as complete contrast-enhancing tumor resection with no measurable residual contrast-enhancing tumor volume and greater than 5 cm³ of non-contrast-enhancing tumor resection. Class 2B is defined as near-total contrast-enhancing tumor resection with residual contrast-enhancing tumor volume of 1.0 cm³ or less. Results for Class 2A and Class 2B will be summarized separately and in aggregate.
Time frame: Within 48 hours postoperatively
Proportion of Subjects Classified as Response Assessment in Neuro-Oncology Resect Class 3 Based on Early Postoperative MRI
Response Assessment in Neuro-Oncology Resect Class 3, also referred to as submaximal contrast-enhancing resection, will be assessed using early postoperative MRI. Class 3 is defined as measurable residual contrast-enhancing tumor volume greater than 1.0 cm³. Class 3A is defined as residual contrast-enhancing tumor volume of 5.0 cm³ or less, and Class 3B is defined as residual contrast-enhancing tumor volume greater than 5.0 cm³. Results for Class 3A and Class 3B will be summarized separately.
Time frame: Within 48 hours postoperatively
Proportion of Subjects With Progression-Free Survival at 3 Months Based on Clinical Evaluation and MRI Assessment Using Response Assessment in Neuro-Oncology Criteria
Progression-free survival at 3 months is defined as the proportion of subjects who remain alive and free from radiographic or clinical progression 3 months after surgical resection. Progression status will be determined by clinical evaluation and MRI assessment using Response Assessment in Neuro-Oncology criteria.
Time frame: 3 months after surgical resection
Proportion of Subjects With Progression-Free Survival at 6 Months Based on Clinical Evaluation and MRI Assessment Using Response Assessment in Neuro-Oncology Criteria
Progression-free survival at 6 months is defined as the proportion of subjects who remain alive and free from radiographic or clinical progression 6 months after surgical resection. Progression status will be determined by clinical evaluation and MRI assessment using Response Assessment in Neuro-Oncology criteria. Time to progression-free survival event, defined as progression or death, will also be summarized.
Time frame: 6 months after surgical resection
Overall Survival at 6 Months
Overall survival at 6 months is defined as the proportion of subjects who remain alive 6 months after surgical resection.
Time frame: 6 months after surgical resection
Detection Accuracy of Near-Infrared Fluorescence Imaging With FG001 Compared With Histopathological Assessment of Brain Tissue
Detection accuracy of near-infrared fluorescence imaging with FG001 will be assessed by comparison with histopathological assessment of brain tissue specimens obtained from the tumor bulk and tumor margin. Specimen-level calculations will include positive predictive value, negative predictive value, sensitivity, and specificity.
Time frame: Intraoperatively and following histopathological assessment
Number of Subjects With Adverse Events, Serious Adverse Events, and Clinically Significant Safety Findings Following FG001 Administration
Safety and tolerability of FG001 will be assessed based on adverse events, clinical laboratory parameters, vital signs, and 12-lead electrocardiogram findings. Adverse events will be monitored from screening through Month 6. Clinical laboratory parameters will be assessed at screening, day of surgery, and Day 7. Vital signs will be assessed from screening through Month 6. Electrocardiograms will be assessed at screening, pre-operatively, day of surgery, Day 3, and Day 7.
Time frame: Adverse events will be monitored from screening, following informed consent, through the Month 6 follow-up visit.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.