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

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

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

Study Overview

• Status: Completed
• Conditions: Esophagogastric Cancer
• Intervention / Treatment: Radiation: 89Zr-DFO-trastuzumab; Device: PET imaging

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Radiation: 89Zr-DFO-trastuzumab; Device: PET imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety as Measured by the Number of Participants Who Experienced Toxicity	Participants will be evaluated for toxicity using CTCAE v4.0	2 years
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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 580 hours

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Neeta Pandit-Taskar, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2013
• Primary Completion (Actual): June 27, 2023
• Study Completion (Actual): June 27, 2023

Study Registration Dates

• First Submitted: December 18, 2013
• First Submitted That Met QC Criteria: December 23, 2013
• First Posted (Estimated): December 30, 2013

Study Record Updates

• Last Update Posted (Actual): December 10, 2024
• Last Update Submitted That Met QC Criteria: November 19, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: PET Imaging; HER2 positive; 89Zr-DFO-trastuzumab; 13-165
• Additional Relevant MeSH Terms: Antineoplastic Agents, Immunological; Antineoplastic Agents; Trastuzumab
• Other Study ID Numbers: 13-165