First combined intravenous and intracerebral application of an oncolytic virus, parvovirus h-1, in a phase I/IIa clinical trial in patients with recurrent glioblastoma multiforme (ParvOryx01).

TPS2111 Background: The management of glioblastoma multiforme (GBM) is an unsolved problem and medium survival has remained at dismal 15 months. Among alternative treatments is the use of oncolytic viruses which preferentially kill tumor cells. Preclinical work using rat glioma models showed that the oncolytic rodent parvovirus H-1PV was able to cure gliomas after single intratumoral or multiple intravenous injections (K. Geletneky et al. Neuro-Oncology 2010), forming the basis for a clinical trial with H-1PV. Methods: ParvOryx01 (NCT01301430) is a dose-escalation phase I/IIa clinical trial treating patients with recurrent GBM with H-1PV. The trial has two arms of 9 patients each, subdivided in 3 dose groups of 1E6, 5E7 and 1E9 pfu H-1PV. In arm A patients first receive an intratumoral injection of H-1PV followed by tumor resection and virus injection in the tumor-surrounding infiltration zone 10 days after the first treatment. In arm B patients receive for the first time in a clinical trial a combined intravenous/intracerebral virus injection. At days 1 to 5 half of the designated dose is injected intravenously followed by tumor resection and virus injection in the peritumoral brain as in arm A. Main inclusion criteria are a single and completely resectable recurrent GBM, 18+ years of age, confirmed diagnosis of GBM (WHO IV), failed previous radio- and/or chemotherapy, Karnofsky Performance Score ≥60, commitment to omit exposure to infants < 18 months of age. Patients have to be isolated during treatment (K. Geletneky et al. BMC Cancer 2012). Arm A has been completed without DLT. As intratumoral injection in arm A led to asymptomatic systemic exposure to H-1PV, arm B can be conducted at the two higher dose levels only. Due to the lack of DLT the trial was amended with 3 additional patients in arm A receiving a high dose of 5E9 pfu. At the moment patients are recruited for Arm B and high-dose arm A. The trial design allows for the in depth analysis of infected tumor tissue and H-1PV penetration into the tumor after systemic injection. Clinical trial information: NCT01301430.