Pancreatic AdenocarcinomaPhase 2VIRAGENCT05673811
Study of Nab-Paclitaxel and Gemcitabine and Plus/Minus VCN-01 in Patients With Metastatic Pancreatic Cancer
A Phase 2 study testing Nab-paclitaxel, Gemcitabine and VCN-01 in people with Pancreatic Adenocarcinoma and Metastatic, run by Theriva Biologics SL at 17 sites in 2 countries.
Trial summary
A phase IIb, open-label, randomized study of Nab-Paclitaxel and Gemcitabine and plus/minus VCN-01 in Patients with Metastatic Pancreatic Cancer Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Adenocarcinoma, Metastatic
- What is being tested?
- Nab-paclitaxel, Gemcitabine and VCN-01
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- 17 sitesin 2 countries
- Study dates
- 10 Jan 2023to 28 Mar 2025
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent obtained prior to any study-specific procedures or assessments.
- Male/female patients aged 18 years or over.
- Patients with histologically or cytologically confirmed, first line metastatic pancreatic adenocarcinoma stage IV de novo, who never received previous systemic treatment for their pancreatic cancer for which the established therapy is nab-paclitaxel/gemcitabine (clinical SoC). All patients must have at least one measurable tumor lesion that can be imaged for assessments determined by RECIST 1.1.
- Patients willing to comply with the study treatment.
- Patients with a minimum life expectancy of 5 months.
- ECOG performance status of 0 or 1.
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- Use of a reliable method of contraception in fertile men and women. Female patients of childbearing potential (i.e., female patients who are not postmenopausal or surgically sterile) must agree to use effective contraception. Male patients must agree to use effective contraception or be surgically sterile. All male patients must use a male condom.
- Adequate baseline organ function (hematologic, liver, renal and nutritional)verified by laboratory analyses performed within 72 hours prior to dosing*:
- Hematology:
- Absolute neutrophil count ≥1.5xE9 /L
- Hemoglobin ≥9 g/dL
- Platelets ≥100xE9/L
- Coagulation (except in patients on anticoagulants):
- Prothrombin time or international normalized ratio ≤1x upper limit of normal (ULN)
- Activated partial thromboplastin time ≤1.2xULN
- Hepatic:
- Total bilirubin ≤1.5xULN
- ALT and AST ≤2.5xULN (if there are no liver metastases)
- ALT and AST <5xULN, and bilirubin <1.5xULN (if there are liver metastases)
- Renal:
- Serum creatinine ≤1.5xULN, and if >1.5xULN: Estimated creatinine clearance >50 mL/min using Cockcroft and Gault formula
- Nutritional:
- Serum Albumin ≥30 g/L
- Note: Adequate organ function specified in this criterion must also be met prior to VCN-01 dosing on Cycle 4 Day 1 for ARM II.
Who cannot join
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- Patients not willing to complete the study procedures for geographic, psychiatric, or social reasons.
- Active infection or other serious illness or autoimmune disease at the moment of randomization. Active infection includes tuberculosis (TB; clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), Hepatitis B Virus (HBV; positive HBV surface antigen [HBsAg] result), Hepatitis C Virus (HCV; positive HCV Ribonucleic acid [RNA]), or human immunodeficiency virus (positive HIV 1/2 antibodies). HBV carriers (patients positive for HBsAg) or those patients requiring antiviral therapy treatment for HBV virus or HCV are not eligible to participate.
- However, the following patients are eligible to participate in the study:
- o Patients with past or resolved TB are eligible;
- o Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) are eligible. Blood HBV DNA must be obtained and must be negative in these patients prior to treatment;
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- o Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- Treatment with live attenuated vaccines in the last 3 weeks and with the adenovirus type-5 (Ad5)-based COVID-vaccine in the last 12 weeks before the administration of study treatment.
- Known chronic liver disease (liver cirrhosis, chronic hepatitis). If there is a suspicion of hepatic fibrosis, a FibroScan must be performed; patients with a value ≥9.5 kPa will be excluded. Note: Transient elastography (Fibroscan) is a non-invasive method for the assessment of hepatic fibrosis.
- Treatment with another investigational agent within five of that treatment's half-lives prior to infusion of study treatment.
- Viral syndrome diagnosed during the 2 weeks before start of study treatment administration.
- Chronic immunosuppressive therapy and/or disease modifying therapy, except inhaled corticosteroids, and oral or IV corticosteroids with a dose lower than 10 mg prednisone or equivalent/day (exception: dexamethasone 1 mg/day as maximum).
- Concurrent malignant hematologic or solid disease. Patients with a prior history of cancer can be allowed if complete remission for at least 3 years.
- Patients in close contact (e.g., living in same house) with immunosuppressed patients (i.e., patients with chronic immunosuppressive therapy including high dose of corticosteroids, patients with acquired immunodeficiency syndrome (AIDS), and other chronic immune system diseases).
- Patients with Li Fraumeni syndrome or with previously known retinoblastoma protein pathway germline deficiency.
- A female patient, who is pregnant or lactating.
- Patients receiving full-dose anticoagulant therapy or in whom these therapies cannot be withdrawn 2 days prior and 2 days after VCN-01 administration. Patients with uncontrolled coagulopathy should be excluded.
- Untreated brain metastases and/or leptomeningeal carcinomatosis with progressive symptoms despite corticosteroid coverage. Patients with brain metastases with stable symptoms can be included.
- Any other condition, disease, metabolic dysfunction (e.g., uncontrolled diabetes mellitus), active or uncontrolled infection/inflammation, physical examination finding, mental state or clinical laboratory finding that would contraindicate participation in the clinical study due to safety concerns or compliance with clinical study procedures.
- Patients with previous pneumonitis or interstitial lung disease.
- Patients with pre-existing sensory neuropathy >G1.
- Patients with known risk factors for bowel perforation.
- Patients with QT interval corrected by Fridericia (QTcF) assessment >450 ms for men or >470 ms for women and left ventricular ejection fraction (LVEF) evaluation less than 50% measured by ECHO or multigated acquisition scan.
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
- Subjects, for whom first line treatment options other than the combination Gemcitabine/Nab-Paclitaxel are recommended by the investigator.
Trial locations and contacts
17 sites in 2 countries.
17 sites in 2 countries
Spain10 sites
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona, 08035
Hospital Duran i Reynals (ICO)
L'Hospitalet de Llobregat, Barcelona, 08908
Hospital Gregorio Marañon
Madrid, Madrid, 28009
Hospital Universitario Ramon y Cajal
Madrid, Madrid, 28034
Hospital Universitario 12 de Octubre
Madrid, Madrid, 28041
Hospital Universitario Virgen de la Victoria
Málaga, Málaga, 29010
Hospital Universitario Marqués de Valdecilla
Santander, Cantabria, 39008
Hospital Universitario Virgen del Rocío
Seville, Andalusia, 41013
Hospital General Univesitario de Valencia
Valencia, Valencia, 46014
Hospital Miguel Servet
Zaragoza, Zaragoza, 50009
United States7 sites
Martha Morehouse Tower
Columbus, Ohio, 43221
Virginia Cancer Specialists
Fairfax, Virginia, 22031
University of Louisville - Brown Cancer Center
Louisville, Kentucky, 40202
Weill Cornell Medical Center
New York, New York, 10065
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92663
University of California - Davis Cancer Center
Sacramento, California, 95817
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, 84112
About this study
Official title: A Phase IIb, Open-label, Randomized Study of Nab-Paclitaxel and Gemcitabine and Plus/Minus VCN-01 in Patients With Metastatic Pancreatic Cancer
A phase IIb, open-label, randomized study of Nab-Paclitaxel and Gemcitabine and plus/minus VCN-01 in Patients with Metastatic Pancreatic Cancer
Read the detailed description
Multi-center, open label, randomized, 2-parallel arm, phase IIb study of nab-paclitaxel and gemcitabine as Standard of Care (SoC) plus/minus VCN-01 in patients with metastatic pancreatic cancer. Gemcitabine and nab-paclitaxel are chemotherapy drugs approved by the FDA to treat pancreatic cancer. VCN-01 is a genetically modified adenovirus characterized by the presence of four independent genetic modifications in the backbone of the wild-type human adenovirus serotype 5 (HAd5) genome that confer tumor selective replication and antitumor activity. Approximately 92 patients in sites in North America and European Union (EU) will be recruited and randomized in a 1:1 ratio to one of two treatment arms (i.e., approximately 46 patients per treatment arm):
- Arm 1- (SoC): Nab-paclitaxel and gemcitabine as SoC (28-day cycles). Patients in this arm will not receive the investigational medicinal product (IMP) VCN-01.
- Arm 2- (VCN-01+ SoC): A maximum of two (2) doses of VCN-01 administrated in combination with nab-paclitaxel and gemcitabine as SoC (28-day cycles with exception of the IMP dose cycles, which will be 35-day cycles).
A Data Monitoring Committee (DMC) will be convened at regular intervals to assess safety and to look at OS to determine if the trial can continue.
- Conditions
- Pancreatic Adenocarcinoma, Metastatic
- Being tested
- Nab-paclitaxel, Gemcitabine, VCN-01
- Keywords
- Cancer, Pancreatic adenocarcinoma, metastatic, oncolytic virus, VCN-01, Gemcitabine, Nab-Paclitaxel
- Medical subject headings
- Neoplasm Metastasis, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nab-paclitaxelDrug
Nab-paclitaxel administered as an IV infusion at a rate of 125 mg/m2. Nab-paclitaxel is administered on Day 1, Day 8 and Day 15 of each 28-day cycles.
GemcitabineDrug
Gemcitabine administered as an IV infusion at a dose of 1,000 mg/m2 immediately after the completion of nab-paclitaxel administration as part of SoC. Gemcitabine is administered on Day 1, Day 8 and Day 15 of each 28-day cycles.
VCN-01Genetic
VCN-01 administrated as a single IV infusion at dose 1xE13 viral particles (vp) on Day 1 of the 1st cycle and then again on Day 1 of the 4th cycle (Day 92). On cycle 1 and cycle 4, nab-paclitaxel and gemcitabine administered on Day 8, Day 15 and Day 22.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1-SoC | Active comparator | Nab-paclitaxel and gemcitabine as SoC. Receives: Drug: Nab-paclitaxel; Drug: Gemcitabine |
| Arm 2 -VCN-01 + SoC | Experimental | A maximum of two (2) doses of VCN-01 administrated as a single IV infusion in combination with nab-paclitaxel and gemcitabine as SoC. Receives: Drug: Nab-paclitaxel; Drug: Gemcitabine; Genetic: VCN-01 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
From date of randomization until the date of death from any cause, assessed up to 27 months
Measured: From date of randomization until the date of death from any cause, assessed up to 27 months
Number of TEAEs in Each Treatment Arm
Safety and tolerability of VCN-01, IV administered at Week 1 and Week 14 in Arm 2 measured as incidence of Adverse Events as assessed by CTCAE v5.0
Measured: until the end of treatment period phase
Secondary outcomes (6)
Time to Progression (TTP) or Progression Free Survival (PFS)
This outcome measure evaluates two related endpoints: Time to Progression (TTP) and Progression-Free Survival (PFS). TTP is defined as the time from randomization to the date of first documented disease progression and assessed up to 27 months. PFS is defined as the time from randomization to the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 27 months.
Measured: TTP: From randomization until documented disease progression assessed up to 27 months. PFS: From randomization to either progression or death from any cause assessed up to 27 months.
Overall Response Rate (ORR)
Objective response rate (ORR) defined as the sum of patients who achieved partial response (PR) plus patients who achieved complete response (CR) using RECIST version 1.1 criteria.
Measured: From randomization to partial response or complete response up to 27 months
Disease Control Rate (DCR)
Disease Control Rate (DCR) defined as: stable disease (SD) + partial response (PR) + complete response (CR)
Measured: From randomization to partial response or complete response up to 27 months
Landmark 1-year Survival
Number of alive participants that were live at the 12-month follow-up period from first enrollment. This measures does not consider the censored patients that had not reached the one-year-Follow-up yet.
Measured: From randomization to 1-year landmark
Number of Patients With Progression Free Survival (PFS) at the 1-year Landmark
Patients that have PFS at the 1-year landmark (n)
Measured: From randomization up to 12 months
Duration of Response (DoR)
Duration of Response (DoR) is defined as the time from the date of first documented objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documented disease progression, or death from any cause, whichever occurs first. This analysis will only include patients who achieved a confirmed objective response.
Measured: From randomization to disease progression assessed up to 27 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2023
- Study start10 Jan 2023
- Primary completion28 Mar 2025
- Study completion28 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pancreatic AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- Theriva Biologics SL
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tara E Seery, MD, Principal investigator, Hoag Memorial Hospital PresbyterianEdward Kim, MD, PhD, Principal investigator, University of California, Davis Cancer CentreVivek R Sharma, MD, FACP, Principal investigator, University of Louisville, Brown Cancer CenterAlana TH Nguyen, MD, PhD, Principal investigator, Weill Medical College of Cornell UniversityArjun Mittra, MD, Principal investigator, Martha Morehouse TowerChristopher Nevala-Plagemann, MD, Principal investigator, Hunstman Cancer Institute, University of UtahAlexander Spira, MD, PhD, Principal investigator, Virginia Cancer SpecialistsRocío García, MD, PhD, Principal investigator, Hospital Universtario 12 de octubre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05673811
- Sponsor's protocol ID
- P-VCNA-003
- Acronym
- VIRAGE
- Status last verified
- Oct 2026
- First submitted
- 3 Nov 2022
- Last updated
- 8 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Garcia-Carbonero R, Pazo Cid R, Macarulla T, Laquente B, Nguyen A, Guillen-Ponce C, Munoz A, Kim EJ, Cazorla M, Seery T, Lobo de Mena M, Nevala-Plagemann C, Sharma V, Martinez de Castro E, Hojouj M, Le C, Mato-Berciano A, Connelly S, Kaleko M, Rojas LA, Wacher VJ, Shallcross MA, Blasco C, Cascallo M, Hidalgo M. Intravenous hyaluronidase-expressing oncolytic adenovirus with chemotherapy in metastatic pancreatic cancer: a randomized phase 2b trial. Nat Med. 2026 Sep 30. doi: 10.1038/s41591-026-04705-y. Online ahead of print.
PubMed 42816596