Parvovirus H-1 (ParvOryx) in Patients With Metastatic Inoperable Pancreatic Cancer

Study Overview
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Brief Summary
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Investigation on safety, tolerability and efficacy of parvovirus H-1 (ParvOryx) in subjects suffering from metastatic, inoperable pancreatic cancer with at least one hepatic metastasis.

Detailed Description
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Investigation on safety, tolerability and efficacy of parvovirus H-1 (ParvOryx) in subjects suffering from metastatic, inoperable pancreatic cancer with at least one hepatic metastasis. Initially four equal doses of ParvOryx will be administered intravenously on four consecutive days. Seven to fourteen days after the first intravenous administration the drug will be injected directly in a hepatic metastasis of the pancreatic cancer.

Official Title
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A Non-controlled, Single Arm, Open Label, Phase II Study of Intravenous and Intratumoral Administration of ParvOryx in Patients With Metastatic, Inoperable Pancreatic Cancer

Conditions
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Carcinoma, Pancreatic Ductal

Intervention / Treatment
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* Drug: Parvovirus H-1 (H-1PV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age at least 18 year, Ability to give informed consent, Histologically confirmed pancreatic ductal adenocarcinoma (PAD) with at least one measurable hepatic metastasis according to RECIST 1.1, Disease progression despite first line therapy (whatever chemotherapy regimen), Eligibility for second line chemotherapy with gemcitabine, ECOG performance scale 0 or 1, Consent for the sampling and investigations of biological specimens as scheduled by the trial protocol, Adequate bone marrow function: neutrophils >1.5 x 1E09/L, platelets >100 x 1E09/L, hemoglobin >9.0 g/dL, Liver function tests (LFT) within the following range: Bilirubin <3 x ULN (Upper Limit of Normal); ASAT and ALAT <5 x ULN, Adequate renal function: Creatinine <1.5 g/dL, Adequate blood clotting: aPTT <39 sec, INR <1.2, Normal thyroid function, i.e. TSH, fT3 and fT4 within the normal range (TSH: 0.4 - 4.0 mU/l, fT3: 2.0 - 4.2 ng/l, fT4: 8 - 18 ng/l) Negative serology for HIV, HBV and HCV, Negative Beta-HCG test in blood in woman of childbearing potential, Use of adequate contraception in both genders, i.e. use of double-effective method of contraception for the entire participation in the trial. Exclusion Criteria: Eligibility for surgical treatment, Symptomatic cerebral, pulmonal, and/or osseous metastases, Peritoneal carcinosis, Liver cirrhosis, Splenectomy, Relevant respiratory impairment, corresponding to the grade IV or V of the MRC Breathlessness Scale (stops for breath after walking about 100 meters or after a few minutes on level ground, or too breathless to leave the house, or breathless when undressing), Positive anti-drug antibodies (ADAs) against ParvOryx, Hospitalization due to other conditions than the pancreatic cancer within the last 3 months, Chemotherapy within 2 weeks prior to the first administration of the IMP, Signs of active, systemic infection within 7 days prior to the study inclusion (clinical symptoms (cough, running nose, burning sensation while urinating, apparent skin or wound infection) and/or increase of fever and/or deterioration of infection-specific laboratory parameters beyond changes apparently driven by the underlying pancreatic cancer), Radiotherapy within 6 weeks prior to the study inclusion, Contraindications for CT, Known allergy to iodinated contrast media, Participation in another interventional trial within the last 30 days, Presumed contact with pregnant women and/or infants <12 months of age within two months after the first administration of the IMP.

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: ParvOryx<br>ParvOryx given intravenously on four consecutive days (day 1 to 4) and intrametastatic six to thirteen days thereafter (day 7, 10 or 14). | Drug: Parvovirus H-1 (H-1PV)<br>* Parvovirus H-1 administered at three increasing dose levels , according to the following schedule: i) 4 daily intravenous infusions of 10% of the total dose over 2 hours on 4 consecutive days, ii) direct injection of 60% of the total dose into a hepatic metastasis of the pancreatic cancer. The total dose levels are: 1E09, 5E09 and 1E10 pfu.<br>* Other names: ParvOryx;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of the IMP | Parameter: findings in physical examinations | Up to 6 months after treatment beginning | 
| Safety and tolerability of the IMP | Parameters: chosen laboratory parameters | Up to 6 months after treatment beginning | 
| Safety and tolerability of the IMP | Parameter: ECG | Up to 6 months after treatment beginning | 
| Safety and tolerability of the IMP | Parameter: adverse events | Up to 6 months after treatment beginning | 
| Humoral immuneresponse to the IMP | Parameter: Serum concentration of anti-drug antibodies (ADA) | Up to 6 months after treatment beginning | 
| Pharmacokinetics of viral genomes [Vg] | Parameter: Cmax in blood | Up to 6 months after treatment beginning | 
| Pharmacokinetics of viral genomes [Vg] | Parameter: AUC in blood | Up to 6 months after treatment beginning | 
| Shedding of viral genomes [Vg] | Parameter: Concentration of Vg in feaces | Up to 6 months after treatment beginning | 
| Shedding of viral genomes [Vg] | Parameter: Concentration of Vg in urine | Up to 6 months after treatment beginning | 
| Shedding of viral genomes [Vg] | Parameter: Concentration of Vg in saliva | Up to 6 months after treatment beginning | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histo-immuno-pathological effects of the IMP in the hepatic metastasis | Parameter: extent of tumor necrosis | Up to 2 months after treatment beginning | 
| Histo-immuno-pathological effects of the IMP in the hepatic metastasis | Parameter: density of tumor infiltrating cells | Up to 2 months after treatment beginning | 
| Histo-immuno-pathological effects of the IMP in the hepatic metastasis | Parameter: tissue content of cytokines | Up to 2 months after treatment beginning | 
| Histo-immuno-pathological effects of the IMP in the hepatic metastasis | Parameter: tissue content of chemokines | Up to 2 months after treatment beginning | 
| Extent of virus replication in the hepatic metastasis | Parameters: quantification of NS-1 protein in the metastatic tissue | Up to 2 months after treatment beginning | 
| Cellular immune response against viral proteins | Parameter: ELISPOT | Up to 6 months after treatment beginning | 
| Cellular immune response against viral proteins | Parameter: FACS | Up to 6 months after treatment beginning | 
| Clinical outcome | Parameters: PFS, OS | Up to 6 months after treatment beginning | 
| Clinical outcome | Parameter: Serum concentration of CA19-9 | Up to 6 months after treatment beginning |