Phase 2 Trial of Oncolytic H-1 Parvovirus Therapy Shows Safety and Signs of Immune System Activation in Patients With Metastatic Pancreatic Ductal Adenocarcinoma.

PURPOSE: To investigate the safety, clinical efficacy, virus pharmacokinetics, shedding, and immune response after administration of an oncolytic parvovirus (H-1PV, ParvOryx) to patients with metastatic pancreatic ductal adenocarcinoma (PDAC) refractory to first-line therapy. PATIENTS AND METHODS: This is a noncontrolled, single-arm, open-label, dose-escalating, single-center clinical trial. Seven patients with PDAC and at least one liver metastasis were included. ParvOryx was administered intravenously on 4 consecutive days and as an intralesional injection, 6 to 13 days thereafter. Altogether, three escalating dose levels were investigated. In addition, gemcitabine treatment was initiated on day 28. RESULTS: ParvOryx showed excellent tolerability with no dose-limiting toxicities. One patient had a confirmed partial response and one patient revealed an unconfirmed partial response according to RECIST criteria. Both patients showed remarkably long surivial of 326 and 555 days, respectively. Investigation of pharmacokinetics and virus shedding revealed dose dependency with no excretion of active virus particles in saliva or urine and very limited excretion in feces. H-1PV nucleic acids were detected in tumor samples of four patients. All patients showed T-cell responses to viral proteins. An interesting immunologic pattern developed in tumor tissues and in blood of both patients with partial response suggesting immune activation after administration of ParvOryx. CONCLUSIONS: The trial met all primary objectives, revealed no environmental risks, and indicated favorable immune modulation after administration of ParvOryx. It can be considered a good basis for further systematic clinical development alone or in combination with immunomodulatory compounds.

Semiautomated aseptic preparation of patient-individual antineoplastic intravenous solutions: first experiences in a German hospital pharmacy.

OBJECTIVES: In 2013, the PharmaHelp device was introduced to daily patient care at the University Hospital of Heidelberg in order to improve process and staff safety and health. It is a semiautomated device located in a safety workbench for aseptic preparation with weight-and-visual-supported process check as well as radio-frequency identification of bags and vials. METHODS: After qualification and a training period, several high-admixture-volume drugs were chosen stepwise to be prepared by the device. During a reporting period of 6 months, the number of processed production runs and produced bags were assessed as well as the productivity per hour of the device based on the processed admixing volume and time consumption for manual preprocessing and postprocessing steps. RESULTS: Weight conformity tests of 246 processed bags in 11 admixing-volume ranges showed 99.19% with a deviation of <5%. Validation of the automated preparation process with 40 media fills showed no microbiological growth. Daily patient care production in the first 6 months led to a nearly similar weight accuracy and an average productivity of 22.5 preparations per running hour of the device at an average admixing volume of 39.6 mL, excluding manual preprocessing and postprocessing tasks. Time consumption for all manual steps was about 76 min per run. CONCLUSIONS: The automated admixing process of the device showed remarkable effectivity and a satisfying accuracy, but the manual preprocessing and postprocessing steps are time consuming, which is associated with the local environment, and has to be reorganised.