The purpose of this study is to determine the safety and tolerability of VCN-01 either administered alone or in combination with Abraxane®/Gemcitabine, and to determine the recommended phase II dose of VCN-01 alone or in combination with Abraxane®/Gemcitabine.
The study consists of three parts: * Part I is a dose escalation study to determine the safety and tolerability of a single intravenous injection of VCN-01 alone * In Part II the safety and tolerability of the two highest VCN-01 tolerable doses from part I will be evaluated in combination with Abraxane®/Gemcitabine. * In Part III the safety and tolerability of the two highest VCN-01 tolerable doses from part I will be evaluated in combination with Abraxane®/Gemcitabine in a "delayed" schedule compared with Part II.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Genetically modified human adenovirus encoding human PH20 hyaluronidase
1000 mg/m2 intravenous administration
125 mg/m2 intravenous administration
Hospital Vall d'Hebron
Barcelona, Spain
Institut Català d'Oncologia
L'Hospitalet de Llobregat, Spain
Centro Integral Oncológico Clara Campal
Madrid, Spain
Hospital Universitario Ramón y Cajal
Madrid, Spain
Safety and Tolerability by means of Adverse Events (AEs) and laboratory data
Time frame: At least 6 months
Recommended Phase 2 Dose (RP2D) by determination of highest feasible dose (MFD) and any Dose Limiting Toxicities
Time frame: At least 6 months
Presence of VCN-01 in tumor
Determination of VCN-01 by analyzing viral genome copies in tumor biopsy
Time frame: Day 8-10
Viral Pharmacokinetics
Determination of VCN-01 half-life by analyzing viral genome copies in blood
Time frame: Up to 48 h
Viral Shedding
And at least up to 6 months follow-up in patients at the Maximum Tolerated Dose (MTD)
Time frame: Up to day 28
Neutralizing antibodies anti-VCN-01
At least up to 6 months follow-up in patients at the MTD
Time frame: 30 days after end of treatment phase
Preliminary anti-tumor activity by Overall Response Rate (ORR)
Time frame: CT or MRI scans every 8 weeks until disease progression
Preliminary anti-tumor activity by Progression Free Survival (PFS)
Time frame: CT or MRI scans every 8 weeks until disease progression
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Hospital Universitario 12 de Octubre
Madrid, Spain