Trial Title:
Study of Nab-Paclitaxel and Gemcitabine and Plus/minus VCN-01 in Patients with Metastatic Pancreatic Cancer
NCT ID:
NCT05673811
Condition:
Pancreatic Adenocarcinoma
Metastatic
Conditions: Official terms:
Adenocarcinoma
Paclitaxel
Gemcitabine
Conditions: Keywords:
Cancer
Pancreatic adenocarcinoma
metastatic
oncolytic virus
VCN-01
Gemcitabine
Nab-Paclitaxel
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Nab-paclitaxel
Description:
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.
Arm group label:
Arm 1-SoC
Arm group label:
Arm 2 -VCN-01 + SoC
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
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.
Arm group label:
Arm 1-SoC
Arm group label:
Arm 2 -VCN-01 + SoC
Intervention type:
Genetic
Intervention name:
VCN-01
Description:
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.
Arm group label:
Arm 2 -VCN-01 + SoC
Summary:
A phase IIb, open-label, randomized study of Nab-Paclitaxel and Gemcitabine and
plus/minus VCN-01 in Patients with Metastatic Pancreatic Cancer
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Written informed consent obtained prior to any study-specific procedures or
assessments.
2. Male/female patients aged 18 years or over.
3. 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.
4. Patients willing to comply with the study treatment.
5. Patients with a minimum life expectancy of 5 months.
6. ECOG performance status of 0 or 1.
7. 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.
8. 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.
Exclusion Criteria:
1. Patients not willing to complete the study procedures for geographic, psychiatric,
or social reasons.
2. 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;
o Patients positive for HCV antibody are eligible only if polymerase chain reaction
is negative for HCV RNA.
3. 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.
4. 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.
5. Treatment with another investigational agent within five of that treatment's
half-lives prior to infusion of study treatment.
6. Viral syndrome diagnosed during the 2 weeks before start of study treatment
administration.
7. 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).
8. Concurrent malignant hematologic or solid disease. Patients with a prior history of
cancer can be allowed if complete remission for at least 3 years.
9. 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).
10. Patients with Li Fraumeni syndrome or with previously known retinoblastoma protein
pathway germline deficiency.
11. A female patient, who is pregnant or lactating.
12. 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.
13. Untreated brain metastases and/or leptomeningeal carcinomatosis with progressive
symptoms despite corticosteroid coverage. Patients with brain metastases with stable
symptoms can be included.
14. 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.
15. Patients with previous pneumonitis or interstitial lung disease.
16. Patients with pre-existing sensory neuropathy >G1.
17. Patients with known risk factors for bowel perforation.
18. 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.
19. Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients.
20. Subjects, for whom first line treatment options other than the combination
Gemcitabine/Nab-Paclitaxel are recommended by the investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hoag Memorial Hospital Presbyterian
Address:
City:
Newport Beach
Zip:
92663
Country:
United States
Facility:
Name:
University of California - Davis Cancer Center
Address:
City:
Sacramento
Zip:
95817
Country:
United States
Facility:
Name:
University of Louisville - Brown Cancer Center
Address:
City:
Louisville
Zip:
40202
Country:
United States
Facility:
Name:
Weill Cornell Medical Center
Address:
City:
New York
Zip:
10065
Country:
United States
Facility:
Name:
Martha Morehouse Tower
Address:
City:
Columbus
Zip:
43221
Country:
United States
Facility:
Name:
Huntsman Cancer Institute, University of Utah
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Facility:
Name:
Virginia Cancer Specialists
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Facility:
Name:
Hospital Universitario Virgen del Rocío
Address:
City:
Sevilla
Zip:
41013
Country:
Spain
Facility:
Name:
Hospital Duran i Reynals (ICO)
Address:
City:
Hospitalet de Llobregat
Zip:
08908
Country:
Spain
Facility:
Name:
Hospital Universitario Marqués de Valdecilla
Address:
City:
Santander
Zip:
39008
Country:
Spain
Facility:
Name:
Hospital Universitari Vall d'Hebron
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Facility:
Name:
Hospital Gregorio Marañon
Address:
City:
Madrid
Zip:
28009
Country:
Spain
Facility:
Name:
Hospital Universitario Ramon y Cajal
Address:
City:
Madrid
Zip:
28034
Country:
Spain
Facility:
Name:
Hospital Universitario 12 de Octubre
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Facility:
Name:
Hospital Universitario Virgen de la Victoria
Address:
City:
Málaga
Zip:
29010
Country:
Spain
Facility:
Name:
Hospital General Univesitario de Valencia
Address:
City:
Valencia
Zip:
46014
Country:
Spain
Facility:
Name:
Hospital Miguel Servet
Address:
City:
Zaragoza
Zip:
50009
Country:
Spain
Start date:
January 10, 2023
Completion date:
April 28, 2025
Lead sponsor:
Agency:
Theriva Biologics SL
Agency class:
Industry
Source:
Theriva Biologics SL
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05673811
