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

Study Overview
=================
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.

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

Conditions
-----------------
Locally Advanced Solid Tumors, Metastatic Solid Tumors, Pancreatic Adenocarcinoma

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


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part I: Dose Escalation, Single Agent<br>Single intravenous injection of VCN-01 oncolytic adenovirus | Genetic: VCN-01<br>* Genetically modified human adenovirus encoding human PH20 hyaluronidase<br>|
| Experimental: Part II: Dose Escalation, Combination<br>Single intravenous injection of VCN-01 oncolytic adenovirus in combination with Abraxane®/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>|
| Experimental: Part III: Dose Escalation, Combination, delayed schedule<br>Single intravenous injection of VCN-01 oncolytic adenovirus in combination with Abraxane®/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?
-----------------
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) 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 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cancer, Solid Tumors, Gemcitabine, Oncolytic virus, Metastatic, Pancreatic cancer