Glioma
Conditions
Keywords
ABY-029, Affibody, Molecular Fluorescence-Guided Surgery, Epidermal Growth Factor Receptor (EGFR)
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.
Interventions
DRUGABY-029
Using a sample size of 6-12 patients, ABY-029 will be administered via single intravenous injection to subjects with recurrent glioma, approximately 1-3 hours prior to surgery. Microdose levels of ABY-029 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. Administration of the study drug is not intended to alter the extent of planned brain tumor resection during the surgical procedure.
Sponsors
Dartmouth College
National Cancer Institute (NCI)
Dartmouth-Hitchcock Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
open label
Intervention model description
Pilot feasibility study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Preoperative diagnosis of recurrent high-grade glioma having EGFR positive tissue from prior surgery. 2. Tumor judged to be suitable for open cranial resection based on preoperative imaging studies. 3. Valid informed consent by subject. 4. Age ≥ 18 years old.
Exclusion criteria
1. Pregnant women or women who are breast feeding. 2. Patients on any experimental anti-EGFR targeted therapies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited and enrolled at 1 academic medical center between February 2017 and June 2021. Of 14 participants enrolled (patients met the inclusion criteria and signed the consent form), a total of 12 received the study drug and started the study across the 3 dose groups: 3 patients in the 1X dose group, 3 patients in the 3X dose group, and 6 patients in the 6X dose group.
Participants by arm
| Arm | Count |
|---|---|
| ABY-029 1X Dose Group A 1X dose of ABY-029 will be administered 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: Using a sample size of 3 patients, ABY-029 will be administered via single intravenous injection to subjects with recurrent glioma, approximately 1-3 hours prior to surgery. Microdose levels of ABY-029 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. Administration of the study drug is not intended to alter the extent of planned brain tumor resection during the surgical procedure. | 3 |
| ABY-029 3X Dose Group A 3X dose of ABY-029 will be administered 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: Using a sample size of 3 patients, ABY-029 will be administered via single intravenous injection to subjects with recurrent glioma, approximately 1-3 hours prior to surgery. Microdose levels of ABY-029 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. Administration of the study drug is not intended to alter the extent of planned brain tumor resection during the surgical procedure. | 3 |
| ABY-029 6X Dose Group A 6X dose of ABY-029 will be administered 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: Using a sample size of 3-6 patients, ABY-029 will be administered via single intravenous injection to subjects with recurrent glioma, approximately 1-3 hours prior to surgery. Microdose levels of ABY-029 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. Administration of the study drug is not intended to alter the extent of planned brain tumor resection during the surgical procedure. | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Total | ABY-029 1X Dose Group | ABY-029 3X Dose Group | ABY-029 6X Dose Group |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 2 Participants | 0 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 1 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 3 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 3 Participants | 2 Participants | 6 Participants |
| Region of Enrollment United States | 12 participants | 3 participants | 3 participants | 6 participants |
| Sex: Female, Male Female | 6 Participants | 2 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Male | 6 Participants | 1 Participants | 3 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 6 |
| other Total, other adverse events | 0 / 3 | 0 / 3 | 0 / 6 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 6 |
Outcome results
Primary
Fluorescence Signal Detection
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.
Time frame: during procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1X Dose Group | Fluorescence Signal Detection | 6.2 Biological variance ratio | Standard Deviation 2.4 |
| 3X Dose Group | Fluorescence Signal Detection | 5.0 Biological variance ratio | Standard Deviation 1.2 |
| 6X Dose Group | Fluorescence Signal Detection | 8.8 Biological variance ratio | Standard Deviation 3.7 |
Secondary
Ex Vivo Fluorescence Intensity
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.
Time frame: post surgical
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1X Dose Group | Ex Vivo Fluorescence Intensity | 61.4 relative fluorescence units | Standard Deviation 25.1 |
| 3X Dose Group | Ex Vivo Fluorescence Intensity | 215.2 relative fluorescence units | Standard Deviation 109.1 |
| 6X Dose Group | Ex Vivo Fluorescence Intensity | 884.1 relative fluorescence units | Standard Deviation 475.4 |
Secondary
Mean Tumor-to-background Ratio
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.
Time frame: during procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1X Dose Group | Mean Tumor-to-background Ratio | 1.7 tumor-to-background ratio | Standard Deviation 0.1 |
| 3X Dose Group | Mean Tumor-to-background Ratio | 2.1 tumor-to-background ratio | Standard Deviation 0.6 |
| 6X Dose Group | Mean Tumor-to-background Ratio | 2.6 tumor-to-background ratio | Standard Deviation 0.7 |