A Phase I Dose Escalation Study of Intratumoral VCN-01 Injections With Gemcitabine and Abraxane® in Patients With Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and tolerability of three intratumoral injections of VCN-01 combined with Abraxane®/gemcitabine, and to determine the recommended phase II dose of VCN-01 combined with Abraxane®/gemcitabine.

Detailed Description
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Investigational treatment is a dose-escalation regimen consisting of three VCN-01 intratumoral injections (once every 28 days at the same dose) in combination with intravenous Abraxane® and gemcitabine.

Official Title
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A Phase I, Multicenter, Open-label, Dose Escalation Study of Intratumoral Injections of VCN-01 Oncolytic Adenovirus With Intravenous Gemcitabine and Abraxane® in Advanced Pancreatic Cancer

Conditions
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Pancreatic Adenocarcinoma, Metastatic Pancreatic Adenocarcinoma

Intervention / Treatment
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* Genetic: VCN-01
* Drug: Gemcitabine
* Drug: Abraxane®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male/Female patients aged 18 years or over Patients must provide written informed consent Life expectancy above 3 months Patients willing to comply with treatment follow-up, and to accept a biopsy at day 29 after initiation of the treatment Patients with histologically confirmed diagnosis of unresectable pancreatic adenocarcinoma with symptoms related to the primary tumor. Abraxane® plus Gemcitabine should be the appropriate standard of care to be administered. 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 Known 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 Patients with Li Fraumeni syndrome or with previous known retinoblastoma protein pathway germinal deficiency

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation, Combination<br>Three intratumoral administrations of VCN-01 oncolytic adenovirus every 28 days in combination with Abraxane® and Gemcitabine. | Genetic: VCN-01<br>* Genetically modified human adenovirus encoding human PH20 hyaluronidase<br>Drug: Gemcitabine<br>* 1000 mg/m2 intravenous administration<br>Drug: Abraxane®<br>* 125 mg/m2 intravenous administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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) of VCN-01 in combination with Gemcitabine and Abraxane® 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 |
| --- | --- | --- |
| Presence of VCN-01 in tumor | Determination of VCN-01 viral genome copies in tumor biopsy | Day 21-28 | 
| Viral Pharmacokinetics | Determination of VCN-01 half-life by analyzing viral genome copies in blood | 48 h | 
| Viral Shedding | At least up to 6 months follow-up in patients at the Maximum Tolerated Dose (MTD) | Up to day 71 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Pancreatic adenocarcinoma, Locally advanced, Metastatic, Gemcitabine, Oncolytic virus, Abraxane®