Gene Therapy for Meningeal Carcinomatosis 
PROTOCOL SYNOPSIS 
Title : Intrathecal Gene Therapy for the Treatment of Leptomeningeal Carcinomatosis 
Objective : 
Primary Objectives: 1) Assess the dynamics of retroviral vectors in the subarachnoid space 
after intraventricular and spinal injection of vector-producer cells. 
2) Evaluate the safety of the approach 
3) Evaluate the antitumor efficacy of this approach in the treatment of 
leptomeningeal carcinomatosis. 
Population : Adult patients (>18 y) with documented leptomeningeal spread of their 
primary cancer who have failed standard therapy for their disease. 
Sample Size : 20 patients in four phases (see Dosage/Treatment) 
Dosage/Treatment : Phase A - 3 patients with intraventricular injection of vector-producer 
cells. CSF sampling for vector titer measurements and ganciclovir 
therapy. 
Phase B - 3 patients with combined intraventricular and spinal injections of 
vector-producer cells, CSF sampling for vector titer measurements and 
ganciclovir therapy. 
Phase C - 4 patients with repeat injections (intraventricular and spinal) of 
vector-producer cells (based on vector titer measurements in phases I and II) and 
ganciclovir therapy. 
Phase D - 10 patients treated with the optimal regimen (based on titer 
measurements in previous phases). 
(At each phase, treatment may be repeated for the same patient). 
DilJ.flli.QIL: 2 years 
Endpoints : Safety Endpoints: Development of grade 4 toxicity not responsive to 
therapy in 2 of 3 patients in phases A-C and 4 consecutive patients in 
phase D would be an endpoint for this specific (and subsequent) phases. 
Efficacy Endpoints: Clinical, radiographic, and cytologic evidence for 
eradication of the leptomeningeal disease within 3 months of follow up. 
Imgstigalm; 
Edward H. Oldfield, M.D., Surgical Neurology Branch, NINDS, N.I.H. 
Zvi Ram, M.D., Surgical Neurology Branch, NINDS, N.I.H. 
Eric M. Oshiro, M.D., Surgical Neurology Branch, NINDS, N.I.H. 
John J. Viola, M.D., Surgical Neurology Branch, NINDS, N.I.H. 
Hetty L. DeVroom, R.N., Surgical Neurology Branch, NINDS, N.I.H. 
Nickolas Patronas, M.D., Department of Radiology, Clinical Center, N.I.H. 
R. Michael Blaese, M.D., Metabolism Branch, NCI, N.I.H. 
Yawen Chiang, Ph.D., Genetic Therapy Inc. 
Sponsor : Genetic Therapy, Inc., Gaithersburg, MD 
[ 596 ] 
Recombinant DNA Research, Volume 18 
