Recombinant DNA Advisory Committee- 9/12-13/94 
RAC and stop patient accrual onto the study. (2) Submit data from preclinical cotton rat 
experiments in which the adenovirus vector is injected directly into the central nervous 
system of pre-immunized animals. These animals will be evaluated 1 week following 
vector administration for evidence of inflammation. (3) Submit a revised Informed 
Consent document incorporating the changes suggested by Mr. Capron. 
Summary 
Drs. Stephen L. Eck and Jane B. Alavi of the University of Pennsylvania Medical Center, 
Philadelphia, Pennsylvania, may conduct gene transfer experiments on 18 subjects (>18 
years of age) with malignant glioma. The adenovirus vector encoding the HSV-TK gene, 
H5.020RSVTK, will be injected by a stereotactic guided technique into brain tumors. 
Afterwards, the patients will receive systemic GCV treatment. Patients eligible to undergo 
a palliative debulking procedure will receive the same treatment followed by resection on 
day 7, and a second dose of the vector intra-operatively. Brain tissues removed by 
resection will be analyzed for adenovirus infection, transgene expression, and signs of 
inflammation. The size and metabolic activity of tumors will be monitored by scanning 
with MRI and PET. The objective of the study is to evaluate the overall safety of this 
treatment and to gain insight into the parameters that may limit the general applicability 
of this approach. 
UX. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED: TREATMENT OF ADVANCED 
MESOTHELIOMA WITH THE RECOMBINANT ADENOVIRUS H5.020RSVTK: A 
PHASE I TRIAL /DYL ALBELDA 
Review-Dr. Straus 
Dr. Walters called on Dr. Straus to present his primary review of the protocol submitted 
by Dr. Steven M. Albelda of the University of Pennsylvania Medical Center, Philadelphia, 
Pennsylvania. Dr. Straus said that this protocol is similar in many aspects to Dr. Eck’s 
protocol for the treatment of brain tumors. This protocol is from the same institution, 
involves the same vector to transduce the same HSV-TK gene, and the same concept of 
using GCV to kill the HSV-TK transduced cells. Many of the issues have been raised and 
answered during the review of the brain tumor protocol. 
Dr. Straus said this proposal is for up to 12 patients with advanced mesothelioma. 
Mesothelioma is a tumor in the lining of the pleural space. It spreads locally and causes 
obstruction and infection for which there are few satisfactory treatments. The patient 
survival from the time of diagnosis is a few years at most. Therefore, a novel approach to 
this disease is very much in order. The patients will have diagnosis performed by biopsy 
through a pleural scope into the pleural space. On the next day, if the biopsy is positive, 
the vector will be administered by a chest tube already in place into the pleural space. 
The vector will be given to 4 cohorts with 3 patients in each group. Each cohort will have 
a log-fold increment of doses ranging from 10 9 to 10 12 pfu. It is hoped that mesothelioma 
and normal pleural cells will be transduced and will express the TK gene. Five days after 
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