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

Uppsala University

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Neuroendocrine Tumors

Treatments: Drug: AdVince

Study type: Interventional

Funder types: Other

Identifiers

NCT02749331

2014-000614-64 (EudraCT Number)

VIRUSNET201401

Details and patient eligibility

About

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.

Full description

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. Secondary objectives include to evaluate the anti-tumoral efficacy of AdVince infusions on metastatic neuroendocrine tumors, to determine the replication profile of AdVince and to determine the humoral (antibody) and cytokine-mediated immune response to AdVince. Minimum 12 and maximum 35 patients will be included, the number is based on the toxicity observed.

Enrollment: 35 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Subject´s written informed consent
2. 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
3. Cancer that is not considered resectable for potential cure or tumor reduction
4. Patent portal vein and adequate liver perfusion
5. Liver dominant disease with involvement of <60% of liver parenchyma
6. Karnofsky performance status of >=70%
7. Life expectancy of >=6 months
8. >=18 years of age
9. Must use a reliable method of contraception if sexually active and of reproductive potential
10. Plasma creatinine <105 ug/ml
11. Aspartate transaminase (AST), Alanine transaminase (ALT) and Alkaline Phosphatase (ALP) <3.0-fold upper limit of normal
12. Total bilirubin <2.0-fold upper limit of normal
13. Prothrombin time (PT)/International Normalized Ratio (INR) <2.0 and Prothromboplastin time (PTT) within normal limits
14. Neutrophils >1500/ml, hemoglobin >100 g/L, platelets >100 000/ml
15. Patients with functioning NET should have cover by somatostatin analog

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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35 participants in 1 patient group

AdVince

Experimental group

Description:

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

Treatment:

Drug: AdVince