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

A Phase I, Multicenter, Open-label, Dose Escalation Study of Intravenous Administration of VCN-01 Oncolytic Adenovirus With or Without Gemcitabine and Abraxane® in Patients With Advanced Solid Tumors

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.

Study Overview

• Status: Completed
• Conditions: Pancreatic Adenocarcinoma; Locally Advanced Solid Tumors; Metastatic Solid Tumors
• Intervention / Treatment: Genetic: VCN-01; Drug: Gemcitabine; Drug: Abraxane®

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 Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Hospitalet De Llobregat, Spain, 08908
    • Institut Catala d'Oncologia
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 25080
    • Centro Integral Oncologico Clara Campal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part I: Dose Escalation, Single Agent; Single intravenous injection of VCN-01 oncolytic adenovirus	Genetic: VCN-01; Genetically modified human adenovirus encoding human PH20 hyaluronidase
Experimental: Part II: Dose Escalation, Combination; Single intravenous injection of VCN-01 oncolytic adenovirus in combination with Abraxane®/Gemcitabine	Genetic: VCN-01; Genetically modified human adenovirus encoding human PH20 hyaluronidase; Drug: Gemcitabine; 1000 mg/m2 intravenous administration; Drug: Abraxane®; 125 mg/m2 intravenous administration
Experimental: Part III: Dose Escalation, Combination, "delayed" schedule; Single intravenous injection of VCN-01 oncolytic adenovirus in combination with Abraxane®/Gemcitabine	Genetic: VCN-01; Genetically modified human adenovirus encoding human PH20 hyaluronidase; Drug: Gemcitabine; 1000 mg/m2 intravenous administration; Drug: Abraxane®; 125 mg/m2 intravenous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
Neutralizing antibodies anti-VCN-01	At least up to 6 months follow-up in patients at the MTD	30 days after end of treatment phase
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
Presence of VCN-01 in tumor	Determination of VCN-01 by analyzing viral genome copies in tumor biopsy	Day 8-10
Viral Pharmacokinetics	Determination of VCN-01 half-life by analyzing viral genome copies in blood	Up to 48 h
Viral Shedding	And at least up to 6 months follow-up in patients at the Maximum Tolerated Dose (MTD)	Up to day 28

Collaborators and Investigators

• Sponsor: Theriva Biologics SL

Publications and helpful links

General Publications

• Garcia-Carbonero R, Bazan-Peregrino M, Gil-Martin M, Alvarez R, Macarulla T, Riesco-Martinez MC, Verdaguer H, Guillen-Ponce C, Farrera-Sal M, Moreno R, Mato-Berciano A, Maliandi MV, Torres-Manjon S, Costa M, Del Pozo N, Martinez de Villarreal J, Real FX, Vidal N, Capella G, Alemany R, Blasi E, Blasco C, Cascallo M, Salazar R. Phase I, multicenter, open-label study of intravenous VCN-01 oncolytic adenovirus with or without nab-paclitaxel plus gemcitabine in patients with advanced solid tumors. J Immunother Cancer. 2022 Mar;10(3):e003255. doi: 10.1136/jitc-2021-003255.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): May 1, 2019
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: January 21, 2014
• First Submitted That Met QC Criteria: January 23, 2014
• First Posted (Estimate): January 27, 2014

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 7, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Gemcitabine; Cancer; Metastatic; Pancreatic cancer; Solid Tumors; Oncolytic virus
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Albumin-Bound Paclitaxel
• Other Study ID Numbers: P-VCNA-001; 2012-005555-16 (EudraCT Number)