Study of Recombinant Adenovirus AdVince in Patients With Neuroendocrine Tumors; Safety and Efficacy

NCT02749331 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: VIRUSNET2014012014-000614-64
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

An open-labelled, uncontrolled, single-center Phase I/IIa clinical study to evaluate the safety of repeated infusions of AdVince into the hepatic artery in patients with metastatic neuroendocrine tumors (NETs), and if possible determination of maximum tolerated dose.

Conditions

Neuroendocrine Tumors

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events (AE) according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.03

  AEs probably or possibly related to the study drug or local injuries caused by the administration procedure. If possible identify dose limiting toxicity (DLT), i.e. grade 4 toxicity of any duration or grade 3 toxicity lasting more than 7 days, excluding flu-like symptoms, according to CTCAE v4.03.Clinically significant changes in laboratory parameters (haematology, blood coagulation, liver function, biochemistry and kidney function) and vital signs (body temperature, heart rate, blood pressure, respiratory rate and consciousness according to Reaction Level Scale from 1985 (RLS-85).

  From screening visit and through study completion, an average time of 18 months.

Secondary Outcomes (12)

• Change in tumor size

  Measured within 4 weeks before first treatment and after 80 +/-14 days (evaluation visit 1)

• Change in tumor size

  Measured within 4 weeks before first treatment and after 214 +/- 14 days (evaluation visit 2)

• Change in tumor metabolic activity

  Baseline value within 24 hrs before first treatment and after 80 +/- 14 days(evaluation visit 1)

• Change in tumor metabolic activity

  Baseline value within 24 hrs before first treatment and after 214 +/- 14 days (evaluation visit 2)

• Progression-free survival (PFS)

  Twelve weeks after 80 days from first treatment (4 treatment cycles) or the corresponding time.

Study Arms (1)

AdVince

EXPERIMENTAL

Dose escalation, minimum 3 patients per dose in Phase I. Dose levels: 1. 10 000 000 000 virus particles 2. 100 000 000 000 virus particles 3. 300 000 000 000 virus particles 4. 1000 000 000 000 virus particles Maximum tolerated dose will be confirmed by 12 additional patients treated at this dose level in Phase IIa.

Drug: AdVince

Interventions

AdVince DRUG

Virus solution for infusion in intrahepatic artery

Also known as: Ad5PeptideTransductionDomain(PTD)(CgA-E1AmiR122)

AdVince

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject´s written informed consent
• Histologically and radiologically confirmed progressive neuroendocrine carcinoma of gastrointestinal, pancreatic or bronchial origin with multiple liver metastases. Progression in Clinical symptoms and tumor growth verified over the last 6 months on CT or MRI
• Cancer that is not considered resectable for potential cure or tumor reduction
• Patent portal vein and adequate liver perfusion
• Liver dominant disease with involvement of \<60% of liver parenchyma
• Karnofsky performance status of \>=70%
• Life expectancy of \>=6 months
• \>=18 years of age
• Must use a reliable method of contraception if sexually active and of reproductive potential
• Plasma creatinine \<105 ug/ml
• Aspartate transaminase (AST), Alanine transaminase (ALT) and Alkaline Phosphatase (ALP) \<3.0-fold upper limit of normal
• Total bilirubin \<2.0-fold upper limit of normal
• Prothrombin time (PT)/International Normalized Ratio (INR) \<2.0 and Prothromboplastin time (PTT) within normal limits
• Neutrophils \>1500/ml, hemoglobin \>100 g/L, platelets \>100 000/ml
• Patients with functioning NET should have cover by somatostatin analog

You may not qualify if:

• Known chronic liver dysfunction Before the development of metastatic cancer (e.g. cirrhosis, chronic hepatitis)
• Active infection, including documented HIV and hepatitis C
• Any viral syndrome diagnosed within the previous 2 weeks
• Chemotherapy within the previous 4 weeks Before the first treatment
• Radiotherapy to the target tumor site within the last 24 weeks from the baseline CT scan
• Concomitant malignancy
• Pregnant or lactating females
• Prior participation in any research protocol that involved administration of adenovirus vectors
• Treatment with any other investigational therapy within the last 4 weeks, organ transplantation prior to treatment, severe cardiovascular, metabolic or pulmonary disease
• Continuing treatment with any other cancer therapy

Sponsors & Collaborators

• Uppsala University: lead

Study Sites (1)

Endocrine Oncology Clinic, Uppsala University Hospital

Uppsala, 752 37, Sweden

Location

MeSH Terms

Conditions

Neuroendocrine Tumors

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Study Officials

• Joakim Crona, MD, PhD

  Uppsala University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2016
• First Posted: April 22, 2016
• Study Start: March 1, 2016
• Primary Completion: August 1, 2025
• Study Completion: December 1, 2025
• Last Updated: December 3, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)