Esophagogastric Cancer
Conditions
Keywords
HER2 positive, PET Imaging, 89Zr-DFO-trastuzumab, 13-165
Brief summary
The purpose of the first group (Group 1) was to find the optimal time for taking pictures after injection of 89Zr-DFO-trastuzumab, to see how long it stayed in the blood, and to see how well it was tolerated. From what the investigators have learned from Group 1, patients in Group 2 no longer need serial scans or serial blood draws. This study is based on a cohort expansion. All data is appropriately reported as there is only one study cohort
Interventions
RADIATION89Zr-DFO-trastuzumab
DEVICEPET imaging
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Registered patient at MSKCC * Age ≥18 years * Pathologically or cytologically confirmed metastatic or primary esophagogastric cancer HER2 positive status by FISH or IHC as currently being implemented for patients with esophagogastric cancer. HER2 overexpression and/or amplification as determined by immunohistochemistry (3+) or FISH (≥2.0) * Measurable or evaluable disease, lesions that have not been previously radiated, with clinically indicated imaging evaluation performed within 4 weeks prior to study entry (CT, MRI, FDG PET or bone scan). Patients requiring concurrent radiation treatment are not eligible unless additional lesions that are not being irradiated and are assessable for targeting are present. * Karnofsky Performance Score ≥ 60 * Ability to understand and willingness to sign informed consent * Negative pregnancy test, to be performed on female patients of childbearing potential within 1week before administration of radioactive material. * Life expectancy of at least three (3) months. * Willingness to use birth control while on study. * The patients will be asked to consent to provide access to data obtained from molecular analysis that has been done on archived tumor tissue that will be correlated with 89Zr-DFO-trastuzumab imaging results. * Concurrent therapy will be allowed.
Exclusion criteria
* Inability to lie still for the duration of the scanning procedure. * Patients with known sensitivity or contraindication to any of the component of 89Zr-DFO-trastuzumab (89Zr or Desferroxamine (DFO) or trastuzumab) * Patients who have received trastuzumab must have at least a washout period for trastuzumab of 14 days, this will not apply to 89Zr-DFO-trastuzumab repeat, post treatment assessment where patients may be receiving trastuzumab. * HIV positive or active hepatitis. * History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to study entry * Hematologic * Platelets \<50K/mcL * ANC \<1.0 K/mcL * Hepatic laboratory values * Bilirubin \>2 x ULN (institutional upper limits of normal), with exception of patients with Gilberts disease. AST/ALT \>2.5 x ULN (institutional upper limits of normal); \>5 x ULN if liver metastasis * Renal laboratory values * Estimated GFR (eGFR) \< 30mL/min/1.73m2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety as Measured by the Number of Participants Who Experienced Toxicity | 2 years | Participants will be evaluated for toxicity using CTCAE v4.0 |
| Feasibility of Antibody-imaging | 2 years | Antibody imaging is considered feasible if 70% of the patients are antibody-imaging positive. Antibody imaging will be considered feasible if 7 or more of the 10 patients in the first cohort are antibody-imaging-positive. We will also require that none of these patients experience severe toxicity attributable to the initial antibody. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biologic Half-time | Up to 580 hours | Samples will be obtained just prior to injection of the 89Zr DFO-trastuzumab tracer this sample will be banked at -80degree C for future testing for Human anti-human antibody/HAHA if altered biodistribution is observed. |
Countries
United States
Participant flow
Pre-assignment details
This study is based on a cohort expansion. All data is appropriately reported as there is only one study cohort
Participants by arm
| Arm | Count |
|---|---|
| PET Imaging With 89Zr-DFO-Trastuzumab Patients will receive 5 mCi + 0.5 mCi of 89Zr-DFO-trastuzumab given IV over 5-10 min. Injection of cold trastuzumab will be mixed with 89Zr-DFO-trastuzumab so that total mass is equal to 50 mg \[1\]. In the first ten patients we wish to obtain normal organ dosimetry, pharmacokinetics & determine optimal imaging time, therefore these patients will undergo imaging at 4 time points post injection, whole body counts & blood draws. Subsequent patients will receive the antibody & will only undergo imaging at a single time point (based on the first 10 patients) & will not have whole body counts or serial bloods for pharmacokinetics. The administration of 89Zr-DFO-trastuzumab to patients undergoing a second study will be identical as for their baseline study. Patients undergoing a second injection will only have one scan that will be performed within 1 day before or 2 days after their optimum imaging time point, determined from their baseline imaging study.
89Zr-DFO-trastuzumab
PET imaging | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 6 |
Baseline characteristics
| Characteristic | PET Imaging With 89Zr-DFO-Trastuzumab |
|---|---|
| Age, Continuous | 61 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 17 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Region of Enrollment United States | 36 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 31 / 36 |
| other Total, other adverse events | 2 / 36 |
| serious Total, serious adverse events | 2 / 36 |
Outcome results
Primary
Feasibility of Antibody-imaging
Antibody imaging is considered feasible if 70% of the patients are antibody-imaging positive. Antibody imaging will be considered feasible if 7 or more of the 10 patients in the first cohort are antibody-imaging-positive. We will also require that none of these patients experience severe toxicity attributable to the initial antibody.
Time frame: 2 years
Population: This study is based on a cohort expansion. All data is appropriately reported as there is only one study cohort
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PET Imaging With 89Zr-DFO-Trastuzumab | Feasibility of Antibody-imaging | Participants with >/= 50% tumor load positivity | 24 Participants |
| PET Imaging With 89Zr-DFO-Trastuzumab | Feasibility of Antibody-imaging | Participants with <50% tumor load positivity | 12 Participants |
Primary
Safety as Measured by the Number of Participants Who Experienced Toxicity
Participants will be evaluated for toxicity using CTCAE v4.0
Time frame: 2 years
Population: This study is based on a cohort expansion. All data is appropriately reported as there is only one study cohort
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PET Imaging With 89Zr-DFO-Trastuzumab | Safety as Measured by the Number of Participants Who Experienced Toxicity | Participants with toxicity | 2 Participants |
| PET Imaging With 89Zr-DFO-Trastuzumab | Safety as Measured by the Number of Participants Who Experienced Toxicity | Participants without toxicity | 34 Participants |
Secondary
Biologic Half-time
Samples will be obtained just prior to injection of the 89Zr DFO-trastuzumab tracer this sample will be banked at -80degree C for future testing for Human anti-human antibody/HAHA if altered biodistribution is observed.
Time frame: Up to 580 hours
Population: This study is based on a cohort expansion. All data is appropriately reported as there is only one study cohort
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PET Imaging With 89Zr-DFO-Trastuzumab | Biologic Half-time | 370 hours |