Back to resultsA Phase I Dose Escalation Study of Intratumoral VCN-01 Injections With Gemcitabine and Abraxane® in Patients With Advanced Pancreatic Cancer
Primary Purpose
Pancreatic Adenocarcinoma, Metastatic Pancreatic Adenocarcinoma
Status
Completed
Phase
Phase 1
Locations
Spain
Study Type
Interventional
Intervention
VCN-01
Gemcitabine
Abraxane®
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Adenocarcinoma focused on measuring Cancer, Pancreatic adenocarcinoma, Locally advanced, Metastatic, Gemcitabine, Oncolytic virus, Abraxane®
Eligibility Criteria
Inclusion Criteria:
- Male/Female patients aged 18 years or over
- Patients must provide written informed consent
- Life expectancy above 3 months
- Patients willing to comply with treatment follow-up, and to accept a biopsy at day 29 after initiation of the treatment
- Patients with histologically confirmed diagnosis of unresectable pancreatic adenocarcinoma with symptoms related to the primary tumor. Abraxane® plus Gemcitabine should be the appropriate standard of care to be administered.
- ECOG Performance status 0 or 1
- Adequate baseline organ function (hematologic, liver, renal and nutritional)
- Use a reliable method of contraception in fertile men and women
Exclusion Criteria:
- Active infection or other serious illness or autoimmune disease
- Treatment with live attenuated vaccines in the last three weeks
- Known chronic liver disease (liver cirrhosis, chronic hepatitis)
- Treatment with another investigational agent within its five half-lives prior to VCN-01 infusion
- Viral syndrome diagnosed during the two weeks before inclusion
- Chronic immunosuppressive therapy
- Known concurrent malignant hematologic or solid disease
- Pregnancy or lactation. Patients must agree to use effective contraception or be surgically sterile.
- Patients receiving full-dose anticoagulant / antiplatelet therapy
- Patients with Li Fraumeni syndrome or with previous known retinoblastoma protein pathway germinal deficiency
Sites / Locations
- Institut Català d'Oncologia
- Centro Integral Oncológico Clara Campal
- Hospital Universitario 12 de Octubre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dose Escalation, Combination
Arm Description
Three intratumoral administrations of VCN-01 oncolytic adenovirus every 28 days in combination with Abraxane® and Gemcitabine.
Outcomes
Primary Outcome Measures
Safety and Tolerability by means of Adverse Events (AEs) and laboratory data
Recommended Phase 2 Dose (RP2D) of VCN-01 in combination with Gemcitabine and Abraxane® by determination of highest feasible dose (MFD) and any Dose Limiting Toxicities
Secondary Outcome Measures
Presence of VCN-01 in tumor
Determination of VCN-01 viral genome copies in tumor biopsy
Viral Pharmacokinetics
Determination of VCN-01 half-life by analyzing viral genome copies in blood
Viral Shedding
At least up to 6 months follow-up in patients at the Maximum Tolerated Dose (MTD)
Neutralizing antibodies anti-VCN-01
At least up to 6 months follow-up in patients at the MTD
Preliminary anti-tumor activity by Overall Response Rate (ORR)
Preliminary anti-tumor activity by Progression Free Survival (PFS)
Full Information
NCT ID
NCT02045589
First Posted
January 21, 2014
Last Updated
September 27, 2018
Sponsor
Theriva Biologics SL
1. Study Identification
Unique Protocol Identification Number
NCT02045589
Brief Title
A Phase I Dose Escalation Study of Intratumoral VCN-01 Injections With Gemcitabine and Abraxane® in Patients With Advanced Pancreatic Cancer
Official Title
A Phase I, Multicenter, Open-label, Dose Escalation Study of Intratumoral Injections of VCN-01 Oncolytic Adenovirus With Intravenous Gemcitabine and Abraxane® in Advanced Pancreatic Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
January 2014 (Actual)
Primary Completion Date
October 2016 (Actual)
Study Completion Date
September 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Theriva Biologics SL
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine the safety and tolerability of three intratumoral injections of VCN-01 combined with Abraxane®/gemcitabine, and to determine the recommended phase II dose of VCN-01 combined with Abraxane®/gemcitabine.
Detailed Description
Investigational treatment is a dose-escalation regimen consisting of three VCN-01 intratumoral injections (once every 28 days at the same dose) in combination with intravenous Abraxane® and gemcitabine.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Adenocarcinoma, Metastatic Pancreatic Adenocarcinoma
Keywords
Cancer, Pancreatic adenocarcinoma, Locally advanced, Metastatic, Gemcitabine, Oncolytic virus, Abraxane®
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose Escalation, Combination
Arm Type
Experimental
Arm Description
Three intratumoral administrations of VCN-01 oncolytic adenovirus every 28 days in combination with Abraxane® and Gemcitabine.
Intervention Type
Genetic
Intervention Name(s)
VCN-01
Intervention Description
Genetically modified human adenovirus encoding human PH20 hyaluronidase
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
1000 mg/m2 intravenous administration
Intervention Type
Drug
Intervention Name(s)
Abraxane®
Intervention Description
125 mg/m2 intravenous administration
Primary Outcome Measure Information:
Title
Safety and Tolerability by means of Adverse Events (AEs) and laboratory data
Time Frame
At least 6 months
Title
Recommended Phase 2 Dose (RP2D) of VCN-01 in combination with Gemcitabine and Abraxane® by determination of highest feasible dose (MFD) and any Dose Limiting Toxicities
Time Frame
At least 6 months
Secondary Outcome Measure Information:
Title
Presence of VCN-01 in tumor
Description
Determination of VCN-01 viral genome copies in tumor biopsy
Time Frame
Day 21-28
Title
Viral Pharmacokinetics
Description
Determination of VCN-01 half-life by analyzing viral genome copies in blood
Time Frame
48 h
Title
Viral Shedding
Description
At least up to 6 months follow-up in patients at the Maximum Tolerated Dose (MTD)
Time Frame
Up to day 71
Title
Neutralizing antibodies anti-VCN-01
Description
At least up to 6 months follow-up in patients at the MTD
Time Frame
30 days after end of treatment phase
Title
Preliminary anti-tumor activity by Overall Response Rate (ORR)
Time Frame
CT or MRI scans every 8 weeks until disease progression
Title
Preliminary anti-tumor activity by Progression Free Survival (PFS)
Time Frame
CT or MRI scans every 8 weeks until disease progression
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male/Female patients aged 18 years or over
Patients must provide written informed consent
Life expectancy above 3 months
Patients willing to comply with treatment follow-up, and to accept a biopsy at day 29 after initiation of the treatment
Patients with histologically confirmed diagnosis of unresectable pancreatic adenocarcinoma with symptoms related to the primary tumor. Abraxane® plus Gemcitabine should be the appropriate standard of care to be administered.
ECOG Performance status 0 or 1
Adequate baseline organ function (hematologic, liver, renal and nutritional)
Use a reliable method of contraception in fertile men and women
Exclusion Criteria:
Active infection or other serious illness or autoimmune disease
Treatment with live attenuated vaccines in the last three weeks
Known chronic liver disease (liver cirrhosis, chronic hepatitis)
Treatment with another investigational agent within its five half-lives prior to VCN-01 infusion
Viral syndrome diagnosed during the two weeks before inclusion
Chronic immunosuppressive therapy
Known concurrent malignant hematologic or solid disease
Pregnancy or lactation. Patients must agree to use effective contraception or be surgically sterile.
Patients receiving full-dose anticoagulant / antiplatelet therapy
Patients with Li Fraumeni syndrome or with previous known retinoblastoma protein pathway germinal deficiency
Facility Information:
Facility Name
Institut Català d'Oncologia
City
L'Hospitalet De Llobregat
State/Province
Barcelona
ZIP/Postal Code
08908
Country
Spain
Facility Name
Centro Integral Oncológico Clara Campal
City
Madrid
ZIP/Postal Code
25080
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
35149591
Citation
Bazan-Peregrino M, Garcia-Carbonero R, Laquente B, Alvarez R, Mato-Berciano A, Gimenez-Alejandre M, Morgado S, Rodriguez-Garcia A, Maliandi MV, Riesco MC, Moreno R, Ginesta MM, Perez-Carreras M, Gornals JB, Prados S, Perea S, Capella G, Alemany R, Salazar R, Blasi E, Blasco C, Cascallo M, Hidalgo M. VCN-01 disrupts pancreatic cancer stroma and exerts antitumor effects. J Immunother Cancer. 2021 Nov;9(11):e003254. doi: 10.1136/jitc-2021-003254.
Results Reference
derived
Learn more about this trial
A Phase I Dose Escalation Study of Intratumoral VCN-01 Injections With Gemcitabine and Abraxane® in Patients With Advanced Pancreatic Cancer
We'll reach out to this number within 24 hrs