STEREOTAXIC INJECTION OF HERPES-SIMPLEX THYMIDINE KINASE VECTOR PRODUCER CELLS (PA317-G1TK1SVNA.7) AND INTRAVENOUS GANCICLOVIR FOR THE TREATMENT OF PROGRESSIVE OR RECURRENT PRIMARY SUPRATENTORIAL PEDIATRIC MALIGNANT BRAIN-TUMORS

This study will evaluate the safety and efficacy of in vivo gene trans fer of the herpes simplex thymidine kinase (HSV-Tk1) gene using PA317/ G1Tk1SvNa.7 vector producer cells (VPC) in pediatric patients with pro gressive or recurrent primary supratentorial malignant brain tumors. I nsertion of the HSV-Tk1 gene confers a sensitivity to the anti-herpes drug ganciclovir. It has been demonstrated that the direct injection o f HSV-Tk vector producer cells into growing tumors in animals can resu lt in their complete destruction with ganciclovir therapy. This select ive destruction of growing tumors in situ is thought to result from th e transfer of the HSV-Tk gene into the tumor cells and the production of toxic ganciclovir metabolites which result from the interaction of HSV-Tk and ganciclovir. This procedure can result in the cure of some experimental animals with limited systemic toxicity due to selective g ene transfer into tumors. This clinical trial will focus on maximizing the relative number of vector producer cells to the tumor mass by ste reotactically injecting VPCs into the tumor mass. Children with progre ssive or recurrent primary supratentorial malignant brain tumor which is accessible to stereotactic injection will be evaluated for the exte nt and location(s) of their disease before being entered into the stud y. Fifteen days after stereotactic injection of the tumor mass, gancic lovir will be administered at 5 mg/kg IV b.i.d. for 14 days. Upon comp letion of the treatment with HSV-Tk1 vector producer cells and gancicl ovir, the patient will be followed monthly for the first three months, then every two months for the next twenty-one months, and annually fo r life thereafter.