Parvovirus H-1 (ParvOryx) in Patients With Metastatic Inoperable Pancreatic Cancer (ParvOryx02)

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

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.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Pancreatic Ductal
• Intervention / Treatment: Drug: Parvovirus H-1 (H-1PV)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
      • National Center for Tumor Diseases (NCT)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age at least 18 year,
2. Ability to give informed consent,
3. Histologically confirmed pancreatic ductal adenocarcinoma (PAD) with at least one measurable hepatic metastasis according to RECIST 1.1,
4. Disease progression despite first line therapy (whatever chemotherapy regimen),
5. Eligibility for second line chemotherapy with gemcitabine,
6. ECOG performance scale 0 or 1,
7. Consent for the sampling and investigations of biological specimens as scheduled by the trial protocol,
8. Adequate bone marrow function: neutrophils >1.5 x 1E09/L, platelets >100 x 1E09/L, hemoglobin >9.0 g/dL,
9. Liver function tests (LFT) within the following range: Bilirubin <3 x ULN (Upper Limit of Normal); ASAT and ALAT <5 x ULN,
10. Adequate renal function: Creatinine <1.5 g/dL,
11. Adequate blood clotting: aPTT <39 sec, INR <1.2,
12. 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)
13. Negative serology for HIV, HBV and HCV,
14. Negative Beta-HCG test in blood in woman of childbearing potential,
15. 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:

1. Eligibility for surgical treatment,
2. Symptomatic cerebral, pulmonal, and/or osseous metastases,
3. Peritoneal carcinosis,
4. Liver cirrhosis,
5. Splenectomy,
6. 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),
7. Positive anti-drug antibodies (ADAs) against ParvOryx,
8. Hospitalization due to other conditions than the pancreatic cancer within the last 3 months,
9. Chemotherapy within 2 weeks prior to the first administration of the IMP,
10. 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),
11. Radiotherapy within 6 weeks prior to the study inclusion,
12. Contraindications for CT,
13. Known allergy to iodinated contrast media,
14. Participation in another interventional trial within the last 30 days,
15. Presumed contact with pregnant women and/or infants <12 months of age within two months after the first administration of the IMP.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ParvOryx; 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); 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.; Other Names: ParvOryx

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Oryx GmbH & Co. KG
• Investigators: Study Director: Bernard Huber, Dr., Oryx GmbH & Co. KG; Principal Investigator: Guy Ungerechts, Prof. Dr. Dr., National Center for Tumor Diseases, Heidelberg

Publications and helpful links

General Publications

• Hajda J, Lehmann M, Krebs O, Kieser M, Geletneky K, Jager D, Dahm M, Huber B, Schoning T, Sedlaczek O, Stenzinger A, Halama N, Daniel V, Leuchs B, Angelova A, Rommelaere J, Engeland CE, Springfeld C, Ungerechts G. A non-controlled, single arm, open label, phase II study of intravenous and intratumoral administration of ParvOryx in patients with metastatic, inoperable pancreatic cancer: ParvOryx02 protocol. BMC Cancer. 2017 Aug 29;17(1):576. doi: 10.1186/s12885-017-3604-y.
• Hajda J, Leuchs B, Angelova AL, Frehtman V, Rommelaere J, Mertens M, Pilz M, Kieser M, Krebs O, Dahm M, Huber B, Engeland CE, Mavratzas A, Hohmann N, Schreiber J, Jager D, Halama N, Sedlaczek O, Gaida MM, Daniel V, Springfeld C, Ungerechts G. Phase 2 Trial of Oncolytic H-1 Parvovirus Therapy Shows Safety and Signs of Immune System Activation in Patients With Metastatic Pancreatic Ductal Adenocarcinoma. Clin Cancer Res. 2021 Oct 15;27(20):5546-5556. doi: 10.1158/1078-0432.CCR-21-1020. Epub 2021 Aug 23.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): May 1, 2018
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: December 4, 2015
• First Submitted That Met QC Criteria: January 8, 2016
• First Posted (Estimate): January 12, 2016

Study Record Updates

• Last Update Posted (Actual): November 21, 2022
• Last Update Submitted That Met QC Criteria: November 16, 2022
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Ductal, Lobular, and Medullary; Pancreatic Neoplasms; Carcinoma, Ductal; Carcinoma, Pancreatic Ductal
• Other Study ID Numbers: ParvOryx02