USDOE Human Subjects Research Database, Fiscal Year 2003

Sloan-Kettering Institute for Cancer Research

Public Information Contact:

Mr. F. Edward Herran
Sponsored Projects, MSKCC Box 40
1275 York Avenue
New York, NY 10021-

Phone: 646-227-3273
Fax: 212-577-0760
E-mail: herranf@mskcc.org

Institutional Review Board (IRB):

Human Subject Projects:

Number of Human Subjects projects reported: 2

SKI-86-ER60407	"Improving Cancer Treatment with Cyclotron Produced Radionuclides"
SKI-95-ER62039	"Pharmacokinetics of Genetically Engineered Antibody Forms Using Positron Emission Tomography"

Project Identifier: SKI-86-ER60407

"Improving Cancer Treatment with Cyclotron Produced Radionuclides"

Principal Investigator: Dr. Steven M. Larson, Sloan-Kettering Institute

Project started in: 1986

Project Funding Information:

Funding for Human Subjects Research:

DOE: Office of Biological and Environmental Research (OBER)

$0.00 (Est.) for: Fiscal Year 2003
Pilot and demonstration projects only, designed to obtain basic physiologic information.

Information on Use of Human Subjects:

This project involves the use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 1

Identifier or number: 91-136A(2)

Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Sloan-Kettering Institute for Cancer Research
Most recent approval: 04/10/01
Explanation of IRB approval:
This protocol was closed for accrual on 4/9/02.

Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects: Fiscal Year 2003

Type(s) of Human Subjects Involvement:

Internal administration of radioactive substances to human subjects:

• Other. Explain:

Pharmacokinetic 5-[124I]iodo-2'-deoxyuridine (IUdR)

Internal use of chemical substances (solid, liquid, or gas) on human subjects:

• Other. Explain:

Radioiodinated 5-[124I]iodo-2'-deoxyuridine (IUdR) for pharmacokinetic studies

Collection of personally identifiable bodily materials (blood or blood products, urine, cells, tissue, teeth, organs, excreta, etc):

• Using bodily materials collected specifically for this project.

(a. Objectives, b. Methodology, c. Ionizing Radiation, Radioactive Substances, or Chemical Substances to which human subjects are exposed, d. Involvement of Human Subjects [d.1. procedures used, d.2. risks if any])

Recurrent Brain Tumor

This project was supported primarily under National Cancer Institute (NCI) funding CA 57599, R. Blasberg, PI but the iodine-124 was prepared with partial support of the DOE grant cited above. The purpose of the study was to assess the uptake of 5-[124I]iodo-2'-deoxyuridine (IUdR), labeled with iodine-124 as a basis for positron emission tomography (PET) imaging of proliferation in patients with recurrent brain tumor. Ten patients were studied. Kinetics were determined using the PET camera and blood samples were drawn.

Although the project primarily involves translational research based on animal imaging, occasional human studies will be performed as demonstration projects of the feasibility of use of a radiotracer for specialized research purposes in human subjects. All studies performed using human studies are carried out under the supervision of the IRB and comply with all applicable regulations.

As these experiments involve only trace amounts of radioactivity, there is minimal risk to the patient, equivalent to that for a standard PET scan. This is incorporated into the informed consent which is part of the IRB approved protocol. As with other documents related to patient care, all such data are part of the patient's medical record and are kept strictly confidential.

Project Identifier: SKI-95-ER62039

"Pharmacokinetics of Genetically Engineered Antibody Forms Using Positron Emission Tomography"

Principal Investigator: Dr. Steven M. Larson, Sloan-Kettering Institute for Cancer Research

Project started in: 1995

Project Funding Information:

Funding for Human Subjects Research:

DOE: Office of Biological and Environmental Research (OBER)

$0.00 (Est.) for: Fiscal Year 2003
Physics of imaging detection, radiochemistry development, and pre-clinical testing in animals formed the bulk of the work in this period; clinical protocols are pending.

Information on Use of Human Subjects:

This project does not involve the use of multiple protocols/subprojects.

Identifier or number: 97-017

Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Sloan-Kettering Institute for Cancer Research
Most recent approval: 02/22/00
Explanation of IRB approval:
Protocol 97-017 closed 2/13/01.

Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects: Fiscal Year 2003

Type(s) of Human Subjects Involvement:

Internal administration of radioactive substances to human subjects:

• Other. Explain:

The protocol involves the study of presurgical patients with colorectal cancer, who will be injected with I-124 A33, a humanized anti-colon antibody. Subjects with primary colorectal cancer will be studied and will undergo imaging with PET at intervals after injection.

Internal use of chemical substances (solid, liquid, or gas) on human subjects:

• For clinical research

Collection of personally identifiable bodily materials (blood or blood products, urine, cells, tissue, teeth, organs, excreta, etc):

• Using bodily materials collected specifically for this project.

Other types of human subjects involvement. Explanation:

Subjects will have human tumors that will be targeted with the radiolabeled genetically engineered antibody.

(a. Objectives, b. Methodology, c. Ionizing Radiation, Radioactive Substances, or Chemical Substances to which human subjects are exposed, d. Involvement of Human Subjects [d.1. procedures used, d.2. risks if any])

The objective of this study is to quantitatively determine the pharmacokinetics of radiolabeled antibodies and genetically engineered antibody forms. Positron emission tomography (PET) will be used for any radionuclide work involving human subjects. I-124 will be the primary radionuclide used. At present, this project will study about 15 patients per year, using positron labeled antibodies I-124 A33, under protocol 97-17 (A. Cohen and S. Larson, Principal Investigators). None of the approvals are complete at this time. All studies will be performed after IRB approval, and will include full disclosure and safeguards of the IRB monitored informed consent process. In addition, we anticipate that the additional work will be performed in animals to study basic aspects of tumor targeting. In general, the types of experiments which are done under the DOE contract are primarily of a basic nature and involve either development in the laboratory of tumor seeking radiochemicals and radiopharmaceuticals or radiochemical production procedures, or the use of the cyclotron. Primarily, we use these tracers in animals to understand biological questions. However, we also have a small number of patients that are studied on occasion as part of a validation project in which the principles of the radiopharmaceutical localization are tested. DOE funding has been used to develop production and chemistry schedules for I-124, as well as detailed imaging physics studies for quantitative PET imaging in phantoms. We have intended I-124 for use in these patient studies. No studies have as yet been done. We have had to delay the implementation of the I-124 human studies for two reasons: a) the ready supply of radiopharmaceutical grade I-124 has not yet been feasible and b) A33 humanized, has still been tested in trials as a non-radioactive form, under other support PO1-CA 33049.

We have developed the production methods so that I-124 is now available on a weekly basis due to Memorial Sloan-Kettering Cancer Center (MSKCC) production on the CS15 cyclotron. About 6 to 8 mCi of I-124 are available through this mechanism. This is sufficient for about one patient per week. We are also developing production through a cooperative research and development agreement (CRADA) with the National Institutes of Health (NIH), which will permit larger amounts of I-124 for more extensive studies.

We have now established a drug master file for the Iodine-124 (DMF 15227) which is available for cross filing with an investigational new drug (IND) held by Ludwig Institute, in collaboration with Sloan Kettering Institute.