A Microdose Evaluation Study of ABY-029 in Recurrent Glioma

Early Phase 1

Completed

Brief Summary: The primary study objective is to determine if microdoses of ABY-029 lead to detectable signals in sampled tissues with an EGFR pathology score ≥ 1 based on histological staining.

The secondary study objective is to assess diagnostic accuracy of ABY-029 detection by iFI and intraoperative probe relative to histopathology diagnosis, and other indicators (e.g. proliferation, infiltration, etc.) as the gold standard, and to measure the molecular uptake and concentration of ABY-029 in resected specimens.

Detailed Description: The investigators plan a sample size of 6-12 patients in this open label, single center, clinical trial of ABY-029. Administration will occur as a single intravenous injection to subjects with recurrent glioma, approximately 1-3 hours prior to surgery.

The protocol is not a safety study since no physiological effects are expected at microdose levels of ABY-029. Rather, doses have been selected to determine if a fluorescence signal can be detected by wide-field imaging technology with a signal-to-noise ratio of 10, which is considered necessary for subsequent assessment of diagnostic performance of ABY-029 as a tumor biomarker sufficient to guide surgical resection in the future. No diagnostic or therapeutic intent is proposed, and administration of the study drug is not intended to alter the extent of planned brain tumor resection during the surgical procedure.

Recruitment & Eligibility

Inclusion Criteria

Preoperative diagnosis of recurrent high-grade glioma having EGFR positive tissue from prior surgery.
Tumor judged to be suitable for open cranial resection based on preoperative imaging studies.
Valid informed consent by subject.
Age ≥ 18 years old.

Exclusion Criteria

Arm && Interventions

Group	Intervention	Description
ABY-029 1X dose group	ABY-029	ABY-029 will be administered at the 1X dose level prior to surgery. Probe will be used in vivo to determine if signal is detectable, and ex vivo tissue pathology will measure extent of binding with EGFR positive tumor tissue.
ABY-029 3X dose group	ABY-029	ABY-029 will be administered at the 3X dose level prior to surgery. Probe will be used in vivo to determine if signal is detectable, and ex vivo tissue pathology will measure extent of binding with EGFR positive tumor tissue.
ABY-029 6X dose group	ABY-029	ABY-029 will be administered at the 6X dose level prior to surgery. Probe will be used in vivo to determine if signal is detectable, and ex vivo tissue pathology will measure extent of binding with EGFR positive tumor tissue.

Primary Outcome Measures

Name	Time	Method
Fluorescence Signal Detection	during procedure	The primary study endpoint is to determine if the fluorescence signal from ABY-029, as measured by Biological Variance Ratio (BVR), can be detected in brain tissue during surgery. This will help researchers determine if ABY-029 functions well for imaging brain tumor tissue during surgery.

Secondary Outcome Measures

Name	Time	Method
Mean Tumor-to-background Ratio	during procedure	A secondary study endpoint is to calculate the ratio of the average (mean) fluorescence intensity of ABY-029 measured in the tumor, to the average (mean) fluorescence intensity of ABY-029 measured in the surrounding tissues in the brain during surgery. This will help researchers determine how well ABY-029 works for imaging tumor tissue.
Ex Vivo Fluorescence Intensity	post surgical	Another secondary study endpoint is to quantify the relationship between the dose of ABY-029 administered and the fluorescence intensity produced by ABY-029 in ex vivo tissue samples after they have been transferred to the pathology department. This endpoint will be measured in relative fluorescence units, and will help researchers conduct analyses on how well ABY-029 works for imaging in tissue following surgery.