Gene Therapy for Meningeal Carcinomatosis 
1.6 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 this therapeutic approach. 
3. ) Evaluate the antitumor efficacy of this approach in the treatment of leptomeningeal 
carcinomatosis. 
The above objectives will be pursued in the initial dose-escalation phases (A-C) of the proposed 
clinical trial as well as in the final phase of the trial. Determination of the objectives will be by 
serial clinical examination, serial CSF evaluation for cytology, vector titers, and tumor markers, 
routine laboratory evaluations, and repeat craniospinal MRI for evaluation of macroscopic tumor 
burden and meningeal enhancement. 
See Appendix V for details. 
2.0 Study Design 
2. 1 Overview 
This is a Phase (I) single site, dose escalating, unblinded study of intrathecal transfer of the herpes 
virus thymidine kinase gene and ganciclovir therapy in patients diagnosed with leptomeningeal 
carcinomatosis from a metastasizing cancer. 
2.2 Number of Patients 
The number of patients for each phase of the study was determined to provide information (safety 
and vector dynamics in the subarachnoid space) before each subsequent phase is initiated. A total 
of 20 patients will be treated, (see section 3.2). 
2.3 Patient Management 
Patients will be treated as inpatients at the Clinical Center, Surgical Neurology Branch, NINDS, 
National Institutes of Health. Potential study patients who demonstrate an interest in participating 
in the study will be scheduled for a screening evaluation to determine their eligibility. Upon 
discharge, patients will be seen as outpatients (every 2 weeks during the first two months and 
monthly thereafter for one year and will be closely monitored for adverse effects or changes in 
clinical status. Follow-up for survival status will continue until death or until a final date for 
follow-up cessation is determined. Patients may receive repeat treatment(s) if they show disease 
progression after an initial response to therapy (see Section 9). 
2.4 S t udy..Pu r aii.Q.n 
We expect to treat all 20 patients within one year. The duration of the study will be two years. 
3.0 Study Treatment 
(Appendix V) 
3.1 Method of Administration 
3.11 Phase A HStk-retro viral vector-producer cells will be injected into the right lateral 
ventricle via an Ommaya reservoir (single injection). (3 patients) 
3.12 Phase B HStk-retro viral vector-producer cells will be injected into the right lateral 
ventricle via an Ommaya reservoir (single injection) and into the lumbar subarachnoid space 
via a spinal catheter (single injection). (3 patients) 
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