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

Carcinoma, Pancreatic Ductal Clinical Trial

— ParvOryx02  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02653313
• Other study ID #: ParvOryx02
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 2015
• Est. completion date: May 2018

Study information

• Verified date: March 2019
• Source: Oryx GmbH & Co. KG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: May 2018
• Est. primary completion date: May 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Pancreatic Ductal

Intervention

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.

Locations

Country	Name	City	State
Germany	National Center for Tumor Diseases (NCT)	Heidelberg	Baden-Württemberg

Sponsors (1)

Lead Sponsor	Collaborator
Oryx GmbH & Co. KG

Country where clinical trial is conducted

Germany, 

References & Publications (2)

Hajda J, Lehmann M, Krebs O, Kieser M, Geletneky K, Jäger D, Dahm M, Huber B, Schöning 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of the IMP	Parameter: findings in physical examinations	Up to 6 months after treatment beginning
Primary	Safety and tolerability of the IMP	Parameters: chosen laboratory parameters	Up to 6 months after treatment beginning
Primary	Safety and tolerability of the IMP	Parameter: ECG	Up to 6 months after treatment beginning
Primary	Safety and tolerability of the IMP	Parameter: adverse events	Up to 6 months after treatment beginning
Primary	Humoral immuneresponse to the IMP	Parameter: Serum concentration of anti-drug antibodies (ADA)	Up to 6 months after treatment beginning
Primary	Pharmacokinetics of viral genomes [Vg]	Parameter: Cmax in blood	Up to 6 months after treatment beginning
Primary	Pharmacokinetics of viral genomes [Vg]	Parameter: AUC in blood	Up to 6 months after treatment beginning
Primary	Shedding of viral genomes [Vg]	Parameter: Concentration of Vg in feaces	Up to 6 months after treatment beginning
Primary	Shedding of viral genomes [Vg]	Parameter: Concentration of Vg in urine	Up to 6 months after treatment beginning
Primary	Shedding of viral genomes [Vg]	Parameter: Concentration of Vg in saliva	Up to 6 months after treatment beginning
Secondary	Histo-immuno-pathological effects of the IMP in the hepatic metastasis	Parameter: extent of tumor necrosis	Up to 2 months after treatment beginning
Secondary	Histo-immuno-pathological effects of the IMP in the hepatic metastasis	Parameter: density of tumor infiltrating cells	Up to 2 months after treatment beginning
Secondary	Histo-immuno-pathological effects of the IMP in the hepatic metastasis	Parameter: tissue content of cytokines	Up to 2 months after treatment beginning
Secondary	Histo-immuno-pathological effects of the IMP in the hepatic metastasis	Parameter: tissue content of chemokines	Up to 2 months after treatment beginning
Secondary	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
Secondary	Cellular immune response against viral proteins	Parameter: ELISPOT	Up to 6 months after treatment beginning
Secondary	Cellular immune response against viral proteins	Parameter: FACS	Up to 6 months after treatment beginning
Secondary	Clinical outcome	Parameters: PFS, OS	Up to 6 months after treatment beginning
Secondary	Clinical outcome	Parameter: Serum concentration of CA19-9	Up to 6 months after treatment beginning