Phase I Dose Escalation Study of Intravenous VCN-01 With or Without Gemcitabine and Abraxane® in Patients With Advanced Solid Tumors

Phase 1

Completed

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

• Registration Number: NCT02045602
• Lead Sponsor: Theriva Biologics SL

Brief Summary

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.

Detailed Description

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 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: 2019-05
• Study Completion: 2020-01
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-07
• Last Update Posted: 2020-10-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

• Male/Female patients aged 18 years or over
• Patients must provide written informed consent
• Part I: Patients with histologically confirmed, locally advanced or metastatic solid tumors. Part II and Part III: Patients with histologically confirmed, pancreatic adenocarcinoma for which the established therapy is Abraxane®/Gemcitabine (clinical standard of care)
• Life expectancy above 3 months
• Patients willing to comply with treatment follow-up
• 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
• 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
• Adequate levels of neutralizing antibodies against adenovirus
• 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
Part III: Dose Escalation, Combination, "delayed" schedule	Abraxane®	Single intravenous injection of VCN-01 oncolytic adenovirus in combination with Abraxane®/Gemcitabine
Part II: Dose Escalation, Combination	VCN-01	Single intravenous injection of VCN-01 oncolytic adenovirus in combination with Abraxane®/Gemcitabine
Part I: Dose Escalation, Single Agent	VCN-01	Single intravenous injection of VCN-01 oncolytic adenovirus
Part II: Dose Escalation, Combination	Abraxane®	Single intravenous injection of VCN-01 oncolytic adenovirus in combination with Abraxane®/Gemcitabine
Part III: Dose Escalation, Combination, "delayed" schedule	VCN-01	Single intravenous injection of VCN-01 oncolytic adenovirus in combination with Abraxane®/Gemcitabine
Part II: Dose Escalation, Combination	Gemcitabine	Single intravenous injection of VCN-01 oncolytic adenovirus in combination with Abraxane®/Gemcitabine
Part III: Dose Escalation, Combination, "delayed" schedule	Gemcitabine	Single intravenous injection of VCN-01 oncolytic adenovirus in combination with Abraxane®/Gemcitabine

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability by means of Adverse Events (AEs) and laboratory data	At least 6 months
Recommended Phase 2 Dose (RP2D) by determination of highest feasible dose (MFD) and any Dose Limiting Toxicities	At least 6 months

Secondary Outcome Measures

Name	Time	Method
Presence of VCN-01 in tumor	Day 8-10	Determination of VCN-01 by analyzing viral genome copies in tumor biopsy
Viral Pharmacokinetics	Up to 48 h	Determination of VCN-01 half-life by analyzing viral genome copies in blood
Viral Shedding	Up to day 28	And 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 (5)

Hospital Universitario Ramón y Cajal; 🇪🇸 Madrid, Spain

Hospital Vall d'Hebron; 🇪🇸 Barcelona, Spain

Centro Integral Oncológico Clara Campal; 🇪🇸 Madrid, Spain

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

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain