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

Overview

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.

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: May 2018

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.

Interventions

  • 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.

Arms, Groups and Cohorts

  • 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).

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Oryx GmbH & Co. KG
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Bernard Huber, Dr., Study Director, Oryx GmbH & Co. KG
    • Guy Ungerechts, Prof. Dr. Dr., Principal Investigator, National Center for Tumor Diseases, Heidelberg

References

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.

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