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

Abstract

Background: Metastatic 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.

Methods: ParvOryx02 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.

Discussion: This 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 registration: ClinicalTrials.gov-ID: NCT02653313 , Registration date: Dec. 4th, 2015.

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

Conflict of interest statement

Ethics approval and consent to participate

The reported trial, including all written information given to patients, has been approved by the Ethics Committee of the Medical Faculty Heidelberg prior to the inclusion of the first subject. The written consent for study participation has to be obtained in written form from each subject prior to the first study-specific procedure.

Date of approval: September 29, 2015.

Ethics Committee’s reference ID: AFmo-207/2015.

Consent for publication

Not applicable.

Competing interests

The ParvOryx02 trial is funded by Oryx GmbH & Co KG, Baldham, Germany.

JH and ML declare no competing interests. OK receives salary from Oryx GmbH & Co KG. MK declares no competing interests. KG holds patents related to H-1PV. DJ declares no competing interests. MD and BH receive salary from Oryx GmbH & Co KG. TS, OS, AS, NH, VD, BL and AA declare no competing interests. JR holds patents related to H-1PV. CE, CS and GU declare no competing interests.

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Figures

Fig. 1

General overview of the course of the trial. The trial consists of three phases: Screening, aiming at verification of patients’ eligibility for the trial; Treatment, in which the IMP is administered and the chosen parameters on safety, tolerability, distribution and biological activity of ParvOryx are investigated; Follow-up, aiming at the long-term assessment of safety, tolerability, biological activity and clinical efficacy of ParvOryx. Abbreviations: i.m.: intrametastatic, i.v.: intravenous, Sub: subjects

Fig. 2

Schedule of the main trial-specific interventions. In order to account for potential time-dependent effects, the trial-specific interventions are to be carried out at different time points. Abbreviations: BPS: biopsy of liver metastasis, LA: local (intrametastatic) administration of ParvOryx, PK: thorough pharmacokinetic investigations, Sub: subject