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

Neuroendocrine Tumors Clinical Trial

— RADNET  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02749331
• Other study ID #: VIRUSNET201401
• Secondary ID: 2014-000614-64
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 2016
• Est. completion date: September 2024

Study information

• Verified date: November 2021
• Source: Uppsala University
• Contact: Magnus Essand, Professor
• Phone: +46184714535
• Email: magnus.essand[@]igp.uu.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 35
• Est. completion date: September 2024
• Est. primary completion date: August 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Neuroendocrine Tumors

Intervention

Drug:
• AdVince
Virus solution for infusion in intrahepatic artery

Locations

Country	Name	City	State
Sweden	Endocrine Oncology Clinic, Uppsala University Hospital	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Uppsala University

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in tumor size	Computer tomography (CT) and/or positron emission tomography (PET) with magnetic resonance imaging (MRI). Assessment based on Response Evaluation Criteria In Solid Tumors (RECIST) or modified RECIST (mRECIST).	Measured within 4 weeks before first treatment and after 80 +/-14 days (evaluation visit 1)
Secondary	Change in tumor size	Computer tomography (CT) and/or positron emission tomography (PET) with magnetic resonance imaging (MRI). Assessment based on Response Evaluation Criteria In Solid Tumors (RECIST) or modified RECIST (mRECIST).	Measured within 4 weeks before first treatment and after 214 +/- 14 days (evaluation visit 2)
Secondary	Change in tumor metabolic activity	Change in hormone levels including chromogranin- A (CgA), chromogranin-B (CgB), neuron specific enolase (NSE) and specific hormones.	Baseline value within 24 hrs before first treatment and after 80 +/- 14 days(evaluation visit 1)
Secondary	Change in tumor metabolic activity	Change in hormone levels including chromogranin- A (CgA), chromogranin-B (CgB), neuron specific enolase (NSE) and specific hormones.	Baseline value within 24 hrs before first treatment and after 214 +/- 14 days (evaluation visit 2)
Secondary	Progression-free survival (PFS)	Number of patients with progression-free survival (PFS).	Twelve weeks after 80 days from first treatment (4 treatment cycles) or the corresponding time.
Secondary	Change in replication profile of AdVince	Replication profile determined by quantification of adenovirus genomic copies in patient´s blood by quantitative real-time polymerase chain reaction (QRT-PCR).	Before and 4hrs after each treatment cycle up to a time period of 214 days.
Secondary	Change in replication profile of AdVince	Replication profile determined by quantification of adenovirus genomic copies in patient´s blood by quantitative real-time polymerase chain reaction (QRT-PCR).	Before and 24hrs after each treatment up to a time period of 214 days.
Secondary	Change in replication profile of AdVince	Replication profile determined by quantification of adenovirus genomic copies in patient´s blood by quantitative real-time polymerase chain reaction (QRT-PCR).	Before and 72hrs after each treatment cycle up to a time period of 214 days.
Secondary	Change in the humoral immune response to AdVince	Detection of anti-adenovirus neutralizing antibodies against adenovirus.	At baseline, after 8+2 days, after 50 +/- 7days, optional after 124 +/- 7days and 184 +/- 7 days.
Secondary	Change in the cytokine-mediated immune response	Measure from patient´s plasma.	At baseline and at 4hrs following each treatment up to a time period of 214 days.
Secondary	Change in the cytokine-mediated immune response	Measure from patient´s plasma.	At baseline and at 24hrs following each treatment up to a time period of 214 days.
Secondary	Change in the cytokine-mediated immune response	Measured from patient´s plasma.	At baseline and at 72hrs following each treatment up to a time period of 214 days.