Parvovirus H-1 (ParvOryx) in Patients With Progressive Primary or Recurrent Glioblastoma Multiforme.

Glioblastoma Multiforme Clinical Trial

— ParvOryx01  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01301430
• Other study ID #: ParvOryx01
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 2011
• Est. completion date: May 2015

Study information

• Verified date: March 2015
• Source: Oryx GmbH & Co. KG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Drug:
• H-1PV
H-1PV administered at three increasing doses either intratumorally or intravenously and then 10 days after the first administration intracerebrally (into the walls of tumor resection cavity).

Locations

Country	Name	City	State
Germany	Department of Neurosurgery, University Hospital Heidelberg	Heidelberg

Sponsors (1)

Lead Sponsor	Collaborator
Oryx GmbH & Co. KG

Country where clinical trial is conducted

Germany, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability	Parameters for assessment of safety and tolerability: physical/neurological examinations (pathological findings as quality and quantity); adverse events (quality and quantity per dose level); vital signs, ECG, laboratory parameters (pathological findings as quality and quantity, for laboratory parameters: descriptive statistics); viral shedding and viral specific antibodies (quantity depicted over time)	Up to 28 days after the first administration of the IMP
Secondary	Efficacy (treatment response)	Parameters for evaluation of efficacy: Progression free survival (PFS) based on modified RECIST-criteria depicted as Kaplan-Meier curve; Overall survival (OS) depicted as Kaplan-Meier curve	Up to 6 months after the first administration of the IMP