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
Number of Human Subjects projects reported: 2
"Improving Cancer Treatment with Cyclotron Produced Radionuclides"
Principal Investigator: Dr. Steven M. Larson, Sloan-Kettering Institute
Project started in: 1986
Funding for Human Subjects Research:
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
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 10
Reporting period for number of human subjects:
Fiscal Year 2001
Type(s) of Human Subjects Involvement:
Recurrent Brian Tumor
This project was supported primarily under 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 IUDR, labeled with Iodine-124 as a basis for PET imaging of proliferation in patients with recurrent brain tumor. 10 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 tracer 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 is part of the patient's medical record and is strictly confidential.
"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
Funding for Human Subjects Research:
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. We plan to re-open the protocol once FDA approval of the reagent is obtained (see abstract below).
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 2001
Type(s) of Human Subjects Involvement:
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 have now established a drug master file for the Iodine-124 (DMF 15227) which is available for cross filing with an IND held by Ludwig Institute, in collaboration with Sloan Kettering Institute. The preparation of the formal IND document for submission is underway, and is planned approximately for 2/2002.