Clinical trial NCT01301430: Parvovirus H-1 (ParvOryx) in Patients With Progressive Primary or Recurrent Glioblastoma Multiforme.
Official title: Phase I/IIa Study of Intratumoral/Intracerebral or Intravenous/Intracerebral Administration of Parvovirus H-1 (ParvOryx) in Patients With Progressive Primary or Recurrent Glioblastoma Multiforme.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Glioblastoma Multiforme
Keywords: Progressive glioblastoma multiforme
Recurrent glioblastoma multiforme
Oncolytic virus
Lead sponsor: Oryx GmbH & Co. KG
Sponsor class: INDUSTRY
First posted: 2011-02-23
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Investigation on safety, tolerability and efficacy of H-1 parvovirus (H-1PV) in subjects suffering from glioblastoma multiforme.

Detailed description: Investigation on safety, tolerability and efficacy of H-1 parvovirus (H-1PV) in subjects suffering from glioblastoma multiforme.

H-1PV will primarily be administered either intratumoral or intravenously. Ten days thereafter a complete or a subtotal tumor resection with a subsequent administration of H-1PV into the walls of the resection cavity will be carried out.

Eligibility criteria: Inclusion Criteria:

* Age over or equal to 18 years old,
* Diagnosis of glioblastoma multiforme,
* Written informed consent,
* Recurrent or progressive disease despite previous radio- and/or chemotherapy,
* Indication for complete or subtotal tumor resection,
* Life expectancy of at least 3 months,
* Consent for sampling and investigation of biological specimens,
* Karnofsky Performance Score over or equal to 60,
* Adequate seizure control,
* Adequate bone marrow function: neutrophils \> 1.5 x 10exp9/L, platelets \> 100 x 10exp9/L, hemoglobin \> 9.0 g/dL,
* Adequate liver function: Bilirubin \< 2.0 g/dL, ASAT, ALAT, AP, GGT \< 3 x ULN,
* Adequate renal function: Creatinine \< 1.8 g/dL,
* Adequate blood clotting: aPTT \< 35 sec, INR \< 1.2,
* Negative serology for HIV, HBV and HCV,
* Negative Beta-HCG test in women of childbearing potential,
* Commitment to use adequate contraception (in both genders) for up to six months after study entry,
* Commitment to omit exposure to infants \< 18 months of age or immunocompromised individuals for up to 28 day after first administration of IMP.

Exclusion Criteria:

* Multifocal disease,
* Evidence of distant tumor metastases,
* Contraindications for MRI,
* Active infection within 5 days prior to the study inclusion,
* Chemotherapy within 4 weeks prior to the study inclusion,
* Radiotherapy within 6 weeks prior to the study inclusion,
* Participation in another interventional trial within the last 30 days,
* Treatment with antiangiogenic substances within 21 days prior to therapy.

Primary outcomes:
measure: Safety and tolerability
timeFrame: Up to 28 days after the first administration of the IMP
Secondary outcomes:
measure: Efficacy (treatment response)
timeFrame: Up to 6 months after the first administration of the IMP
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: Department of Neurosurgery, University Hospital Heidelberg
Study officials:
affiliation: Department of Neurosurgery, University Hospital Heidelberg
name: Andreas Unterberg, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Oryx GmbH & Co. KG
name: Bernard Huber, Dr.
role: STUDY_DIRECTOR
References:
citation: Geletneky K, Huesing J, Rommelaere J, Schlehofer JR, Leuchs B, Dahm M, Krebs O, von Knebel Doeberitz M, Huber B, Hajda J. Phase I/IIa study of intratumoral/intracerebral or intravenous/intracerebral administration of Parvovirus H-1 (ParvOryx) in patients with progressive primary or recurrent glioblastoma multiforme: ParvOryx01 protocol. BMC Cancer. 2012 Mar 21;12:99. doi: 10.1186/1471-2407-12-99.
citation: Geletneky K, Leoni AL, Pohlmeyer-Esch G, Loebhard S, Baetz A, Leuchs B, Roscher M, Hoefer C, Jochims K, Dahm M, Huber B, Rommelaere J, Krebs O, Hajda J. Pathology, organ distribution, and immune response after single and repeated intravenous injection of rats with clinical-grade parvovirus H1. Comp Med. 2015 Feb;65(1):23-35.
citation: Geletneky K, Leoni AL, Pohlmeyer-Esch G, Loebhard S, Leuchs B, Hoefer C, Jochims K, Dahm M, Huber B, Rommelaere J, Krebs O, Hajda J. Bioavailability, biodistribution, and CNS toxicity of clinical-grade parvovirus H1 after intravenous and intracerebral injection in rats. Comp Med. 2015 Feb;65(1):36-45.
citation: Geletneky K, Hajda J, Angelova AL, Leuchs B, Capper D, Bartsch AJ, Neumann JO, Schoning T, Husing J, Beelte B, Kiprianova I, Roscher M, Bhat R, von Deimling A, Bruck W, Just A, Frehtman V, Lobhard S, Terletskaia-Ladwig E, Fry J, Jochims K, Daniel V, Krebs O, Dahm M, Huber B, Unterberg A, Rommelaere J. Oncolytic H-1 Parvovirus Shows Safety and Signs of Immunogenic Activity in a First Phase I/IIa Glioblastoma Trial. Mol Ther. 2017 Dec 6;25(12):2620-2634. doi: 10.1016/j.ymthe.2017.08.016. Epub 2017 Aug 24.