Safety Study of Radio-labeled huA33 Antibody in Colorectal Cancer

May 26, 2023 updated by: Memorial Sloan Kettering Cancer Center

A Pilot Study of Radioimmunodetection of 124-Iodine-labeled Humanized A33 Antibody (124I-huA33) in Patients With Colorectal Cancer

The purpose of this study is to determine whether our drug, 124I-huA33, can safely detect colorectal cancer.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This is an open-label, pilot study of a single 4mCi-10mCi/10mg IV dose of 124I-huA33 in patients with colorectal cancer. Patients will be studied with 124I-huA33 positron-emission tomography (PET), and in the subset of patients scheduled for surgery, based on clinical indications, ex vivo quantitation of tumor uptake will also be performed. Patients will receive a single intravenous or intraarterial infusion of 4 mCi-10mCi /10mg 124I-huA33 in 5-30ml of 5% human serum albumin (HSA), over 5-10 minutes. Patient will either receive the 124I-huA33 intravenously (IV) or intraarterially (IA) to determine if there is an advantage of the IV vs the IA route. Following injection with 124I-huA33, on study days 2, 3, and/ or 4, patients will have the option to receive up to 2g/1kg of Immune Globulin (IVIG).

Blood samples will be obtained for pharmacokinetic analysis at 5, 15, 60, and 120 minutes after completion of IV or IA infusion, on day 2, 3, and/ or 4, and before and after the PET scan on the day of surgery or last imaging day (day 8 + 3). Patients scheduled for surgery will undergo a PET scan of the abdomen and pelvis 1-6 hours prior to surgery.

In those patients undergoing surgery, surgery (or biopsy) will be scheduled to occur day 8 (± 3 days) days after administration of 124I-huA33. Biopsy sites may include tumor, tumor bed, regional nodes, portal, suprapancreatic, celiac nodes and the retroperitoneum. Tumor and normal tissue obtained at surgery (or biopsy), and serum will be measured for estimation of percent-injected dose per gram of tumor, normal liver, and serum. Tissue samples will be obtained for autoradiography and immunohistochemistry as an additional assessment of tumor targeting.

Blood samples to determine immunogenicity will be taken at baseline and at 4 weeks.

Toxicity assessments will be made throughout the study period.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Primary or metastatic colorectal carcinoma, histologically confirmed at Memorial Sloan-Kettering Cancer Center (MSKCC).
  • Patients must be candidates for clinically indicated surgery/biopsy for primary/metastatic colorectal cancer
  • Expected survival of at least 3 months.
  • Karnofsky performance status ≥ 70 (ECOG 0 or 1).
  • The following laboratory results within the last 2 weeks prior to study day 1:

Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelet count ≥ 75 x 109/L Serum bilirubin ≤ 2.5 mg/dL Serum creatinine ≤ 2.0 mg/dL White Blood Count (WBC) ≥ 3,000/mm3 Age ≥ 18 years. Children of all ages are not included as colon cancer is extremely rare in children.

  • Women of childbearing potential with confirmed negative pregnancy test on the day of administration of study agent.
  • Before any trial-specific procedures or treatment can be performed, the patient or patient's legally authorized guardian or representative must give witnessed written informed consent for participation in the tria

Exclusion Criteria:

  • Clinically significant cardiac disease (New York Heart Association Class III/IV).
  • Active CNS tumor involvement. Previous treatment with A33 or its fragment and/or a positive test for huA33 HAHA.
  • Lack of availability for immunological and clinical follow-up assessments.
  • Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
  • Women who are pregnant or breast-feeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Radio-labeled huA33 Antibody

Patients will receive a single I-V infusion of 4mCi-10mCi/10mg 124I-huA33 in 5-30 mL of 5% human serum albumin (HAS) in normal saline, over 5 minutes-4 hours. Patients will be studied with 124I-huA33 positron-emission tomography (PET) and ex-vivo quantitation of tumor uptake .

Blood samples will be obtained for pharmacokinetic analysis at 5, 15, 60, and 120 minutes after completion of IV, on and before or after PET scanning on subsequent days.

Surgery (or biopsy) will be scheduled to occur 8- 10 days after administration of 124I-huA33. The 8-10 day imaging session will be scheduled for the morning of surgery or biopsy, approximately 1-6 hours before the procedure.
Drug: Iodine-124 labeled humanized A33 (antibody)
Patients will receive a single intravenous or intraarterial infusion of 10mg huA33, labeled with 4mCi-10mCi of 124I in 5-30ml of 5% HSA in normal saline (NS), over 5-10 minutes. On study days 2, 3, and/or 4 patients will have the option to receive up to 2g/kg of IVIG. Patients will be evaluated with 124I-huA33 positron-emission tomography (PET) with ex vivo quantitation of tumor uptake.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To determine and quantify tumor uptake of radiolabeled antibody from measurements with:
Time Frame: Until end of study
Until end of study
PET imaging/Dosimetry
Time Frame: Until end of study
Until end of study
Autoradiographs - tumor or biopsy samples
Time Frame: Until end of study
Until end of study
Ex vivo radioactivity estimates - tumor, normal tissue and serum samples
Time Frame: Until end of study
Until end of study
Toxicity defined by NCI Common Toxicity Criteria
Time Frame: Until end of study
Until end of study

Secondary Outcome Measures

Outcome Measure
Time Frame
Serum radioactivity, volume of distribution, and half-life following IV and IA 124I-huA33
Time Frame: Until end of study
Until end of study
HAHA levels - measured by plasmon resonance surface (Biacore®) assay
Time Frame: Until end of study
Until end of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

Ludwig Institute for Cancer Research

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2004

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

September 13, 2005

First Submitted That Met QC Criteria

September 13, 2005

First Posted (Estimated)

September 20, 2005

Study Record Updates

Last Update Posted (Actual)

May 31, 2023

Last Update Submitted That Met QC Criteria

May 26, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 03-124

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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