A Phase I Dose Escalation Study of Intratumoral VCN-01 Injections With Gemcitabine and Abraxane® in Patients With Advanced Pancreatic Cancer

Phase 1

Completed

• Conditions: Pancreatic Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma
• Interventions: Genetic: VCN-01; Drug: Gemcitabine; Drug: Abraxane®

• Registration Number: NCT02045589
• Lead Sponsor: Theriva Biologics SL

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.

Study Timeline

• Study Start: 2014-01
• Study First Submitted: 2014-01-21
• Study First Submitted QC: 2014-01-23
• Study First Posted: 2014-01-27
• Primary Completion: 2016-10
• Status Verified: 2018-09
• Study Completion: 2018-09
• Last Update Submitted: 2018-09-27
• Last Update Posted: 2018-10-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dose Escalation, Combination	VCN-01	Three intratumoral administrations of VCN-01 oncolytic adenovirus every 28 days in combination with Abraxane® and Gemcitabine.
Dose Escalation, Combination	Gemcitabine	Three intratumoral administrations of VCN-01 oncolytic adenovirus every 28 days in combination with Abraxane® and Gemcitabine.
Dose Escalation, Combination	Abraxane®	Three intratumoral administrations of VCN-01 oncolytic adenovirus every 28 days in combination with Abraxane® and Gemcitabine.

Primary Outcome Measures

Name	Time	Method
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	At least 6 months
Safety and Tolerability by means of Adverse Events (AEs) and laboratory data	At least 6 months

Secondary Outcome Measures

Name	Time	Method
Presence of VCN-01 in tumor	Day 21-28	Determination of VCN-01 viral genome copies in tumor biopsy
Viral Pharmacokinetics	48 h	Determination of VCN-01 half-life by analyzing viral genome copies in blood
Viral Shedding	Up to day 71	At least up to 6 months follow-up in patients at the Maximum Tolerated Dose (MTD)
Neutralizing antibodies anti-VCN-01	30 days after end of treatment phase	At least up to 6 months follow-up in patients at the MTD
Preliminary anti-tumor activity by Overall Response Rate (ORR)	CT or MRI scans every 8 weeks until disease progression
Preliminary anti-tumor activity by Progression Free Survival (PFS)	CT or MRI scans every 8 weeks until disease progression

Trial Locations

Locations (3)

Institut Català d'Oncologia; 🇪🇸 L'Hospitalet De Llobregat, Barcelona, Spain

Centro Integral Oncológico Clara Campal; 🇪🇸 Madrid, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain