Safety Study of Radio-labeled huA33 Antibody in Colorectal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Ludwig Institute for Cancer Research
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00199862
First received: September 13, 2005
Last updated: March 28, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention
Colorectal Neoplasms
Colorectal Cancer
Colorectal Tumor
COlorectal Carcinoma
Drug: Iodine-124 labeled humanized A33 (antibody)

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: A Pilot Study of Radioimmunodetection of 124-Iodine-labeled Humanized A33 Antibody (124I-huA33) in Patients With Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To determine and quantify tumor uptake of radiolabeled antibody from measurements with: [ Time Frame: Until end of study ] [ Designated as safety issue: No ]
  • PET imaging/Dosimetry [ Time Frame: Until end of study ] [ Designated as safety issue: No ]
  • Autoradiographs - tumor or biopsy samples [ Time Frame: Until end of study ] [ Designated as safety issue: No ]
  • Ex vivo radioactivity estimates - tumor, normal tissue and serum samples [ Time Frame: Until end of study ] [ Designated as safety issue: No ]
  • Toxicity defined by NCI Common Toxicity Criteria [ Time Frame: Until end of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Serum radioactivity, volume of distribution, and half-life following IV and IA 124I-huA33 [ Time Frame: Until end of study ] [ Designated as safety issue: No ]
  • HAHA levels - measured by plasmon resonance surface (Biacore®) assay [ Time Frame: Until end of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: February 2004
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00199862

Locations
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Ludwig Institute for Cancer Research
Investigators
Principal Investigator: Steven M Larson, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00199862     History of Changes
Other Study ID Numbers: 03-124
Study First Received: September 13, 2005
Last Updated: March 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
huA33
antibody
colorectal cancer
Iodine 124
124I
03-124

Additional relevant MeSH terms:
Neoplasms
Carcinoma
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antibodies
Immunoglobulins
Iodine
Cadexomer iodine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Trace Elements
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on July 24, 2014