' 
MEDICAL 
RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• Adult Patient or • Parent, for Minor Patient 
institute: NiNDs Informed Consent 
STUDY NUMBER: PRINCIPAL INVESTIGATOR: JEdward H. Oldfield, M.D. 
STUDY TITLE: _ Intrathecal Gene Therapy for the Treatment of Leptomeningeal Carcinomatosis 
Phase A INTRODUCTION 
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We invite you to take part in a research study at the National Institutes of Health. It is important that you read and 
understand several general principles that apply to all who take part in our studies: (a) taking part in the study is entirely 
voluntary; (b) personal benefit may not result from taking part in the study, but knowledge may be gained that will 
benefit others; (c) you may withdraw from the study at any time without penalty or loss of any benefits to which you are 
otherwise entitled. The nature of the study, the risks, inconveniences, discomforts, and other pertinent information about 
the study are discussed below. You are urged to discuss any questions you have about this study with the staff members 
who explain it to you. 
Leptomeningeal carcinomatosis (LMC) is the spread of malignant tumor cells along the 
membranes that cover the brain and spinal cord. There is no effective treatment for this 
condition when it recurs after radiation therapy and chemotherapy. Therefore, we have 
developed a new experimental approach that takes advantage of knowledge gained in the fields 
of genetics and gene therapy. A virus that causes mouth sores and other types of infections is 
called herpes simplex. It can be treated with a drug called Cytovene. Herpes simplex is killed by 
Cytovene because the virus contains a specific gene called the Herpes-thymidine kinase gene 
(TK gene). The TK gene has been isolated in the laboratory and in experiments has been 
injected into tumor cells in the lining of spinal cords in rats. This causes the spinal cord tumor 
cells containing the TK gene to be killed when the rats are treated with Cytovene. Rats treated 
this way had slower progression of paralysis and survived longer than untreated rats with the 
same tumors of the spinal cord lining. 
The purpose of this study is to gain information about whether or not this new approach is 
safe and effective in treating human tumors of the spinal cord lining. Although the findings in 
animals are encouraging, you will be one of the first humans to receive this investigational 
treatment for LMC. While we hope to gain information on the usefulness of this approach in 
humans, we cannot know whether your tumor will get smaller as a result of this experimental 
treatment. It is possible that this experimental treatment could make you worse. 
WHAT IS GENE THERAPY FOR LMC? 
We will attempt to change the genetic material of tumor cells in the lining of your brain and 
spinal cord by inserting the TK gene into the tumor cells. The way we will transport the TK gene 
into the tumor cells is to use a “vehicle” to carry the TK gene into the cells. An example is that if 
you want to move a passenger you need to put him in a car. The vehicle (or car) in this case is a 
different virus - a retrovirus that is found in mice - that has been inactivated so that it can not 
cause disease. We call this vehicle a “vector”. We insert the TK gene (the passenger) into the 
vector and the vector carries the gene into your brain tumor cells. The vector/gene combination 
5A7IENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL 
RESEARCH STUDY 
•Adult Patient or •Parent, for Minor Patient 
G?0 3 11-327 
NIH-2514-1 (10-84) P.m.. u j-to-0099 
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Recombinant DNA Research, Volume 18 
