Clinical trial NCT02045602: Phase I Dose Escalation Study of Intravenous VCN-01 With or Without Gemcitabine and Abraxane® in Patients With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Locally Advanced Solid Tumors
Metastatic Solid Tumors
Pancreatic Adenocarcinoma
Keywords: Cancer
Solid Tumors
Gemcitabine
Oncolytic virus
Metastatic
Pancreatic cancer
Lead sponsor: Theriva Biologics SL
Sponsor class: INDUSTRY
First posted: 2014-01-27
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and Tolerability by means of Adverse Events (AEs) and laboratory data
timeFrame: At least 6 months
measure: Recommended Phase 2 Dose (RP2D) by determination of highest feasible dose (MFD) and any Dose Limiting Toxicities
timeFrame: At least 6 months
Secondary outcomes:
measure: Presence of VCN-01 in tumor
timeFrame: Day 8-10
measure: Viral Pharmacokinetics
timeFrame: Up to 48 h
measure: Viral Shedding
timeFrame: Up to day 28
measure: Neutralizing antibodies anti-VCN-01
timeFrame: 30 days after end of treatment phase
measure: Preliminary anti-tumor activity by Overall Response Rate (ORR)
timeFrame: CT or MRI scans every 8 weeks until disease progression
measure: Preliminary anti-tumor activity by Progression Free Survival (PFS)
timeFrame: CT or MRI scans every 8 weeks until disease progression
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Hospitalet De Llobregat
country: Spain
facility: Institut Català d'Oncologia
city: Madrid
country: Spain
facility: Centro Integral Oncológico Clara Campal
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
Study officials:
References:
citation: 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.