PET Imaging With 89Zr-DFO-Trastuzumab in Esophagogastric Cancer

Study Overview
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Brief Summary
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This study is divided into two groups. 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. For Group 2, the patient will receive the injection of 89Zr-DFO-trastuzumab and will be monitored following the injection. The patient will be asked to return for a picture 5-8 days after injection to determine how well the study drug attaches to your tumor and how well it is tolerated

Official Title
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Pilot Trial of PET Imaging With 89Zr-DFO-Trastuzumab in Esophagogastric Cancer

Conditions
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Esophagogastric Cancer

Intervention / Treatment
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* Radiation: 89Zr-DFO-trastuzumab
* Device: PET imaging


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PET Imaging With 89Zr-DFO-Trastuzumab<br>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. | Radiation: 89Zr-DFO-trastuzumab<br> <br> Device: PET imaging<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity | (CTCAE v4) Incidence and nature and severity of adverse events; and change in vital signs and clinical laboratory results. Incidence and severity of adverse events will be summarized with descriptive statistics. | 2 years | 
| feasibility | 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. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| metabolite analysis | 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 immune response (HAHA) if altered biodistribution is observed., and at 5 ± 2 minutes, 15 ± 5, 30 ± 9, 60 ± 19 minutes, and 120 - 240 minutes after the injection of the tracer 1, and at the time of each subsequent day of imaging. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2 positive, PET Imaging, 89Zr-DFO-trastuzumab, 13-165