Phase I Dose Escalation Study Of Intravenous VCN-01 With Or Without Gemcitabine And Abraxane® In Patients With Advanced Solid Tumors

Study Overview

Phase I Dose Escalation Study of Intravenous VCN-01 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.

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 ⋞layed" schedule compared with Part II.

Locally Advanced Solid Tumors
Metastatic Solid Tumors
Pancreatic Adenocarcinoma

GENETIC: VCN-01
DRUG: Gemcitabine
DRUG: Abraxane®

P-VCNA-001
2012-005555-16 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2014-01-21	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2020-10-07
First Submitted that Met QC Criteria 2014-01-23	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2020-10-08
First Posted (ACTUAL) 2014-01-27	Results First Posted N/A	Last Verified 2020-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Single Group

Masking:
None

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

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

Primary Outcome Measures	Measure Description	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	Measure Description	Time Frame
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
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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

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.

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