A non-controlled, single arm, open label, phase II study of intravenous and intratumoral administration of ParvOryx in patients with metastatic, inoperable pancreatic cancer: ParvOryx02 protocol

BMC Cancer

Study Protocol

Tilman Schöning¹  Jacek Hajda²  Monika Lehmann²  Assia Angelova³  Jean Rommelaere³  Barbara Leuchs³  Dirk Jäger⁴  Christine E. Engeland⁴  Christoph Springfeld⁴  Guy Ungerechts⁴  Karsten Geletneky⁵  Albrecht Stenzinger⁶  Oliver Sedlaczek⁷  Volker Daniel⁸  Meinhard Kieser⁹  Bernard Huber^1,10  Ottheinz Krebs^1,10  Michael Dahm^1,10  Niels Halama^1,11 

[1] Central Pharmacy, University Hospital Heidelberg, Im Neuenheimer Feld 670, 69120, Heidelberg, Germany;Coordination Centre for Clinical Trials, University Hospital Heidelberg, Marsilius-Arkaden, Tower West, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany;Department of Applied Tumor Virology, German Cancer Research Center, Im Neuenheimer Feld 242, 69120, Heidelberg, Germany;Department of Medical Oncology, National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, 69120, Heidelberg, Germany;Department of Neurosurgery, Klinikum Darmstadt, Grafenstraße 9, 64283, Darmstadt, Germany;Department of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany;Department of Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany;Institute of Immunology, Transplantation Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany;Institute of Medical Biometry and Informatics, University Hospital Heidelberg, Marsilius-Arkaden, Tower West, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany;Oryx GmbH & Co KG, Marktplatz 1, 85598, Baldham, Germany;Tissue Imaging & Analysis Center (TIGA), University Heidelberg – BioQuant, Im Neuenheimer Feld 267, 69120, Heidelberg, Germany;

关键词: H-1 parvovirus;    Parvovirus;    Oncolytic virotherapy;    Pancreatic cancer;    Pancreatic ductal adenocarcinoma;    PDAC;    Clinical protocol;   

DOI  :  10.1186/s12885-017-3604-y

 received in 2016-04-22, accepted in 2017-08-24,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundMetastatic pancreatic cancer has a dismal prognosis, with a mean six-month progression-free survival of approximately 50% and a median survival of about 11 months. Despite intensive research, only slight improvements of clinical outcome could be achieved over the last decades. Hence, new and innovative therapeutic strategies are urgently required. ParvOryx is a drug product containing native parvovirus H-1 (H-1PV). Since H-1PV was shown to exert pronounced anti-neoplastic effects in pre-clinical models of pancreatic cancer, the drug appears to be a promising candidate for treatment of this malignancy.MethodsParvOryx02 is a non-controlled, single arm, open label, dose-escalating, single center trial. In total seven patients with pancreatic cancer showing at least one hepatic metastasis are to be treated with escalating doses of ParvOryx according to the following schedule: i) 40% of the total dose infused intravenously in equal fractions on four consecutive days, ii) 60% of the total dose injected on a single occasion directly into the hepatic metastasis at varying intervals after intravenous infusions. The main eligibility criteria are: age ≥ 18 years, disease progression despite first-line chemotherapy, and at least one hepatic metastasis. Since it is the second trial within the drug development program, the study primarily explores safety and tolerability after further dose escalation of ParvOryx. The secondary objectives are related to the evaluation of certain aspects of anti-tumor activity and clinical efficacy of the drug.DiscussionThis trial strongly contributes to the clinical development program of ParvOryx. The individual hazards for patients included in the current study and the environmental risks are addressed and counteracted adequately. Besides information on safety and tolerability of the treatment after further dose escalation, thorough evaluations of pharmacokinetics and intratumoral spread as well as proof-of-concept (PoC) in pancreatic cancer will be gained in the course of the trial.Trial registrationClinicalTrials.gov-ID: NCT02653313, Registration date: Dec. 4th, 2015.

【 授权许可】

CC BY   
© The Author(s). 2017