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

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

Detailed Description
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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.

Official Title
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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.

Conditions
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Glioblastoma Multiforme

Intervention / Treatment
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* Drug: H-1PV


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: H-1 parvovirus (H-1PV)<br> | Drug: H-1PV<br>* 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).<br>* Other names: ParvOryx (brand name of H-1PV);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Progressive glioblastoma multiforme, Recurrent glioblastoma multiforme, Oncolytic virus