USDOE Human Subjects Research Database, Fiscal Year 2000

Sloan-Kettering Institute for Cancer Research

Public Information Contact:

Mr. William J. McLoughlin
Sponsored Projects, MSKCC Box 40
1275 York Avenue
New York, NY 10021-

Phone: 646-227-3273
Fax: 212-577-0760
E-mail: mcloughw@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)

$12,000.00 (Est.) for: Fiscal Year 2000
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: 2

Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Sloan-Kettering Institute for Cancer Research
Most recent approval: 04/11/00

Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 11
Reporting period for number of human subjects: Fiscal Year 2000 (10/1/99-9/30/2000)

Type(s) of Human Subjects Involvement:

Internal administration of radioactive substances to human subjects:

• Other. Explain:

Pharmacokinetic IUdR

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

• Other. Explain:

Radioiodinated IUdR for pharmacokinetic studies

Collection of personally identifiable bodily materials (blood or blood products, urine, cells, tissue, teeth, organs, excretia, 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])

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 do 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.

For example, Iodoexyuridine (IUdR), radiolabeled with I-131 and I-125 may be injected into the hepatic artery of patients with colorectal cancer. The purpose of the study will be to obtain biodistribution and biokinetic data in order to understand the dosimetry of IUdR in radiolabeled form. Also, the biology of targeting and clearance are determined. Kinetics are determined using a conjugate view gamma camera.

Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Sloan-Kettering Institute for Cancer Research
Most recent approval: 11/26/96
Explanation of IRB approval:
This protocol was closed 5/12/98

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 2000 (10/1/99-9/30/2000)

Type(s) of Human Subjects Involvement:

Internal administration of radioactive substances to human subjects:

• For clinical research
• For diagnostic research
• Other. Explain:

I-123, I-131, IUdR and I-124 IUdR for the assessment of DNA synthesis in vivo

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

• Other. Explain:

Lugol's solution to block thyroid uptake

Collection of personally identifiable bodily materials (blood or blood products, urine, cells, tissue, teeth, organs, excretia, 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])

The objective of this protocol is to demonstrate: a) the feasibility and validity of imaging tumor cell proliferation with a radiolabeled analogue of thymidine, I-124 iododeoxyuridine (I-124 IUdR), and positron emission tomography (PET); b) that treatment response can be assessed in the "early" post-treatment period by I-124 IUdR and PET prior to changes observed on magnetic resonance (MR) or computerized tomographic (CT) imaging; and c) that the "early" post-treatment assessment with I-124 IUdR and PET correlates with patient survival.

This protocol is safe and effective for research applications as defined under 21 CFR 361.1.

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 do 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.

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 2000
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:
Waiting for FDA approval of reagent, protocol on hold.

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 2000 (10/1/99-9/30/2000)

Type(s) of Human Subjects Involvement:

Internal administration of radioactive substances to human subjects:

• Other. Explain:

Basic pharmacology of radiolabeled genetically engineered forms

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, excretia, 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 2 reasons: a) the ready supply of radiopharmaceutical grade I-124 has not yet been feasible; 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 MSKCC production on the CS15 cyclotron. About 6 to 8 mCi of I-124 are available through this mechanism. This is sufficient for about 1 patient per week. We are also developing production through a CRADA with NIH, which will permit larger amounts of I-124 for more extensive studies.

The FDA reorganization act of November 1998 has caused us some delay in final approval of this labeled antibody. We anticipate that FDA will have resolved the review process by January 2000.

We intend to implement this trial as soon as FDA grants approval of the IND. Approximately 15 patients are planned to be studied under this protocol.