Locally Advanced Solid Tumors, Metastatic Solid Tumors, Pancreatic Adenocarcinoma
Conditions
Keywords
Cancer, Solid Tumors, Gemcitabine, Oncolytic virus, Metastatic, Pancreatic cancer
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.
Interventions
Sponsors
Theriva Biologics SL
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Viral Shedding | Up to day 28 | And at least up to 6 months follow-up in patients at the Maximum Tolerated Dose (MTD) |
| Neutralizing antibodies anti-VCN-01 | 30 days after end of treatment phase | At least up to 6 months follow-up in patients at the MTD |
| Presence of VCN-01 in tumor | Day 8-10 | Determination of VCN-01 by analyzing viral genome copies in tumor biopsy |
| Preliminary anti-tumor activity by Progression Free Survival (PFS) | CT or MRI scans every 8 weeks until disease progression | — |
| Preliminary anti-tumor activity by Overall Response Rate (ORR) | CT or MRI scans every 8 weeks until disease progression | — |
| Viral Pharmacokinetics | Up to 48 h | Determination of VCN-01 half-life by analyzing viral genome copies in blood |
Countries
Spain
Outcome results
None listed