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

• Sponsor: VCN Biosciences, S.L. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02045602
• Collaborator: (none)
• Enrollment: 42
• Locations: 5
• Arms: 3
• Actual Duration (Months): 72
• Patients Per Site: 8.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced Solid Tumors; Metastatic Solid Tumors; Pancreatic Adenocarcinoma	Genetic: VCN-01; Drug: Gemcitabine; Drug: Abraxane®	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jan 1, 2014
• Actual Primary Completion Date: May 1, 2019
• Actual Study Completion Date: Jan 1, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Safety and Tolerability by means of Adverse Events (AEs) and laboratory data [At least 6 months]

2. Recommended Phase 2 Dose (RP2D) by determination of highest feasible dose (MFD) and any Dose Limiting Toxicities [At least 6 months]

Secondary Outcome Measures

1. Presence of VCN-01 in tumor [Day 8-10]

   Determination of VCN-01 by analyzing viral genome copies in tumor biopsy

2. Viral Pharmacokinetics [Up to 48 h]

   Determination of VCN-01 half-life by analyzing viral genome copies in blood

3. Viral Shedding [Up to day 28]

   And at least up to 6 months follow-up in patients at the Maximum Tolerated Dose (MTD)

4. 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

5. Preliminary anti-tumor activity by Overall Response Rate (ORR) [CT or MRI scans every 8 weeks until disease progression]

6. Preliminary anti-tumor activity by Progression Free Survival (PFS) [CT or MRI scans every 8 weeks until disease progression]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Vall d'Hebron	Barcelona		Spain	08035
2	Institut Català d'Oncologia	Hospitalet De Llobregat		Spain	08908
3	Centro Integral Oncológico Clara Campal	Madrid		Spain	25080
4	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
5	Hospital Universitario 12 de Octubre	Madrid		Spain	28041

Sponsors and Collaborators

• VCN Biosciences, S.L.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: VCN Biosciences, S.L.
• ClinicalTrials.gov Identifier: NCT02045602
• Other Study ID Numbers: P-VCNA-001; 2012-005555-16
• First Posted: Jan 27, 2014
• Last Update Posted: Oct 8, 2020
• Last Verified: Oct 1, 2020

• Keywords provided by VCN Biosciences, S.L.: Cancer; Solid Tumors; Gemcitabine; Oncolytic virus; Metastatic; Pancreatic cancer
• Additional relevant MeSH terms: Neoplasms; Gemcitabine; Albumin-Bound Paclitaxel

Study Results

No Results Posted as of Oct 8, 2020