Parvovirus H-1 (ParvOryx) in Patients With Progressive Primary or Recurrent Glioblastoma Multiforme. (ParvOryx01)

• ClinicalTrials.gov Identifier: NCT01301430
• Recruitment Status: Completed
• First Posted: February 23, 2011
• Last Update Posted: November 21, 2022
• Sponsor: Oryx GmbH & Co. KG
• Information provided by (Responsible Party): Oryx GmbH & Co. KG

Tracking Information

• First Submitted Date: February 21, 2011
• First Posted Date: February 23, 2011
• Last Update Posted Date: November 21, 2022
• Study Start Date: September 2011
• Actual Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 22, 2011)

Safety and tolerability [ Time Frame: Up to 28 days after the first administration of the IMP ]

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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 22, 2011)

Efficacy (treatment response) [ Time Frame: Up to 6 months after the first administration of the IMP ]

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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.
• 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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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).

Other Name: ParvOryx (brand name of H-1PV)

Study Arms

Experimental: H-1 parvovirus (H-1PV)

Intervention: Drug: H-1PV

Publications *

• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 19, 2013): 18
• Original Estimated Enrollment (submitted: February 22, 2011): 19
• Actual Study Completion Date: May 2015
• Actual Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT01301430
• Other Study ID Numbers: ParvOryx01
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Oryx GmbH & Co. KG
• Original Responsible Party: Dr. Karsten Geletneky (principal investigator), Department of Neurosurgery, University Hospital Heidelberg
• Current Study Sponsor: Oryx GmbH & Co. KG
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Andreas Unterberg, Prof. Dr.; Department of Neurosurgery, University Hospital Heidelberg
• Study Director: Bernard Huber, Dr.; Oryx GmbH & Co. KG

• PRS Account: Oryx GmbH & Co. KG
• Verification Date: March 2015