Brain Neoplasm, Malignant Glioma
Conditions
Brief summary
This study is a phase 1-2 trial that evaluates the best dose of cetuximab-IRDye 800CW and how well it works in detecting tumors in patients with malignant glioma who are undergoing surgery. Cetuximab-IRDye 800CW is an optical imaging agent that may help detect tumor cells when a special camera is used.
Detailed description
This is a dose-escalation study of cetuximab-IRDye 800CW. Patients are assigned to 1 of 2 cohorts. COHORT I: Patients receive cetuximab intravenously (IV) over 30 minutes and a lower dose of cetuximab IRDye800 IV over 30 minutes to 1 hour on day 0. COHORT II: Patients receive cetuximab IV over 30 minutes and a higher dose of cetuximab IRDye800 IV over 30 minutes to 1 hour on day 0. All patients undergo standard of care surgical resection of tumor on days 2-5. After completion of study, patients are followed up at days 10 and 30. PRIMARY OBJECTIVE: Determine the efficacy of cetuximab-IRDye 800CW (cetuximab IRDye800) in intraoperatively identifying malignant glioma compared to surrounding normal central nervous system tissue, as measured by tumor-to-background ratio. SECONDARY OBJECTIVE: Determine the tolerability of the cetuximab IRDye800 as an imaging agent in subjects undergoing resection of malignant glioma.
Interventions
BIOLOGICALCetuximab
Administered intravenously (IV)
DRUGCetuximab-IRDye 800CW
Administered intravenously (IV)
PROCEDURETumor resection
Standard of care treatment
Sponsors
National Cancer Institute (NCI)
Eben Rosenthal
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Suspected brain tumors to undergo removal (surgical resection) as standard of care, as assessed by the operating surgeon * Life expectancy of \> 12 weeks * Karnofsky performance status of at least 70% or Eastern Cooperative Oncology Group (ECOG)/Zubrod level 1 * Hemoglobin ≥ 9 gm/dL * Platelet count ≥ 100,000/mm³ * Magnesium, potassium and calcium \> the lower limit of normal per institution normal lab values * Thyroid-stimulating hormone (TSH) \< 13 micro international units/mL
Exclusion criteria
* Received an investigational drug within 30 days prior to first dose of cetuximab IRDye800 * Within 6 months prior to enrollment, myocardial infarction (MI); cerebrovascular accident (CVA); uncontrolled congestive heart failure (CHF); significant liver disease; or unstable angina * History of infusion reactions to cetuximab or other monoclonal antibody therapies * Evidence of QT prolongation on pretreatment electrocardiogram (ECG) (greater than 440 ms in males or greater than 450 ms in females) * Receiving class IA (quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents * Pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor to Background Ratio (TBR) | 1 day | Tumor to background ratios (TBR) will be generated from still images by comparing the relative fluorescence of normal and tumor tissue. The average fluorescence will be compared to the average fluorescence of the surrounding tissue using the paired student's T test for each specimen. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events | Up to 30 days | The incidence of serious and non-serious adverse events is reported as the number of adverse events (Grade 2 or higher), as graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Data are reported by number of events by treatment level. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (Cetuximab, Lower Dose Cetuximab-IRDye 800, Surgery) Patients receive cetuximab IV over 30 minutes and a lower dose of cetuximab IRDye800 IV over 30 minutes to 1 hour on day 0.
All patients undergo standard of care surgical resection of tumor on days 2 to 5.
Cetuximab: Given IV
Cetuximab-IRDye 800CW: Given IV
Conventional Surgery: Undergo tumor resection
Laboratory Biomarker Analysis: Correlative studies | 2 |
| Cohort 2 (Cetuximab, Higher Dose Cetuximab-IRDye 800, Surgery) Patients receive cetuximab IV over 30 minutes and a higher dose of cetuximab IRDye800 IV over 30 minutes to 1 hour on day 0.
All patients undergo standard of care surgical resection of tumor on days 2 to 5.
Cetuximab: Given IV
Cetuximab-IRDye 800CW: Given IV
Conventional Surgery: Undergo tumor resection
Laboratory Biomarker Analysis: Correlative studies | 1 |
| Total | 3 |
Baseline characteristics
| Characteristic | Cohort 1 (Cetuximab, Lower Dose Cetuximab-IRDye 800, Surgery) | Cohort 2 (Cetuximab, Higher Dose Cetuximab-IRDye 800, Surgery) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 2 participants | 1 participants | 3 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 1 |
| other Total, other adverse events | 2 / 2 | 1 / 1 |
| serious Total, serious adverse events | 0 / 2 | 0 / 1 |
Outcome results
Primary
Tumor to Background Ratio (TBR)
Tumor to background ratios (TBR) will be generated from still images by comparing the relative fluorescence of normal and tumor tissue. The average fluorescence will be compared to the average fluorescence of the surrounding tissue using the paired student's T test for each specimen.
Time frame: 1 day
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1 (Cetuximab, Lower Dose Cetuximab-IRDye 800, Surgery) | Tumor to Background Ratio (TBR) | 1.39 Fluorescence Tumor to background ratio |
| Cohort 2 (Cetuximab, Higher Dose Cetuximab-IRDye 800, Surgery) | Tumor to Background Ratio (TBR) | 2.65 Fluorescence Tumor to background ratio |
Secondary
Incidence of Adverse Events
The incidence of serious and non-serious adverse events is reported as the number of adverse events (Grade 2 or higher), as graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Data are reported by number of events by treatment level.
Time frame: Up to 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Cetuximab, Lower Dose Cetuximab-IRDye 800, Surgery) | Incidence of Adverse Events | 0 Adverse events |
| Cohort 2 (Cetuximab, Higher Dose Cetuximab-IRDye 800, Surgery) | Incidence of Adverse Events | 0 Adverse events |