Clinical trial NCT02653313: Parvovirus H-1 (ParvOryx) in Patients With Metastatic Inoperable Pancreatic Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Carcinoma, Pancreatic Ductal
Lead sponsor: Oryx GmbH & Co. KG
Sponsor class: INDUSTRY
First posted: 2016-01-12
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety and tolerability of the IMP
timeFrame: Up to 6 months after treatment beginning
measure: Safety and tolerability of the IMP
timeFrame: Up to 6 months after treatment beginning
measure: Safety and tolerability of the IMP
timeFrame: Up to 6 months after treatment beginning
measure: Safety and tolerability of the IMP
timeFrame: Up to 6 months after treatment beginning
measure: Humoral immuneresponse to the IMP
timeFrame: Up to 6 months after treatment beginning
measure: Pharmacokinetics of viral genomes [Vg]
timeFrame: Up to 6 months after treatment beginning
measure: Pharmacokinetics of viral genomes [Vg]
timeFrame: Up to 6 months after treatment beginning
measure: Shedding of viral genomes [Vg]
timeFrame: Up to 6 months after treatment beginning
measure: Shedding of viral genomes [Vg]
timeFrame: Up to 6 months after treatment beginning
measure: Shedding of viral genomes [Vg]
timeFrame: Up to 6 months after treatment beginning
Secondary outcomes:
measure: Histo-immuno-pathological effects of the IMP in the hepatic metastasis
timeFrame: Up to 2 months after treatment beginning
measure: Histo-immuno-pathological effects of the IMP in the hepatic metastasis
timeFrame: Up to 2 months after treatment beginning
measure: Histo-immuno-pathological effects of the IMP in the hepatic metastasis
timeFrame: Up to 2 months after treatment beginning
measure: Histo-immuno-pathological effects of the IMP in the hepatic metastasis
timeFrame: Up to 2 months after treatment beginning
measure: Extent of virus replication in the hepatic metastasis
timeFrame: Up to 2 months after treatment beginning
measure: Cellular immune response against viral proteins
timeFrame: Up to 6 months after treatment beginning
measure: Cellular immune response against viral proteins
timeFrame: Up to 6 months after treatment beginning
measure: Clinical outcome
timeFrame: Up to 6 months after treatment beginning
measure: Clinical outcome
timeFrame: Up to 6 months after treatment beginning
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: National Center for Tumor Diseases (NCT)
state: Baden-Württemberg
Study officials:
affiliation: Oryx GmbH & Co. KG
name: Bernard Huber, Dr.
role: STUDY_DIRECTOR
affiliation: National Center for Tumor Diseases, Heidelberg
name: Guy Ungerechts, Prof. Dr. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.