- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02749331
Study of Recombinant Adenovirus AdVince in Patients With Neuroendocrine Tumors; Safety and Efficacy (RADNET)
November 4, 2021 updated by: Uppsala University
Study of Recombinant Adenovirus (AdVince) in Patients With Neuroendocrine Tumors; Safety and Efficacy
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.
Study Overview
Detailed 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.
Study Type
Interventional
Enrollment (Anticipated)
35
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Magnus Essand, Professor
- Phone Number: +46184714535
- Email: magnus.essand@igp.uu.se
Study Contact Backup
- Name: Di Yu, PhD
- Phone Number: +46707204196
- Email: di.yu@igp.uu.se
Study Locations
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Uppsala, Sweden, 752 37
- Recruiting
- Endocrine Oncology Clinic, Uppsala University Hospital
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Contact:
- Joakim Crona, MD, PhD
- Phone Number: +46186114917
- Email: joakim.crona@medsci.uu.se
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 100 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: AdVince
Dose escalation, minimum 3 patients per dose in Phase I. Dose levels:
Maximum tolerated dose will be confirmed by 12 additional patients treated at this dose level in Phase IIa. |
Virus solution for infusion in intrahepatic artery
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Adverse Events (AE) according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.03
Time Frame: From screening visit and through study completion, an average time of 18 months.
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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).
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From screening visit and through study completion, an average time of 18 months.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in tumor size
Time Frame: Measured within 4 weeks before first treatment and after 80 +/-14 days (evaluation visit 1)
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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).
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Measured within 4 weeks before first treatment and after 80 +/-14 days (evaluation visit 1)
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Change in tumor size
Time Frame: Measured within 4 weeks before first treatment and after 214 +/- 14 days (evaluation visit 2)
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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).
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Measured within 4 weeks before first treatment and after 214 +/- 14 days (evaluation visit 2)
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Change in tumor metabolic activity
Time Frame: Baseline value within 24 hrs before first treatment and after 80 +/- 14 days(evaluation visit 1)
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Change in hormone levels including chromogranin- A (CgA), chromogranin-B (CgB), neuron specific enolase (NSE) and specific hormones.
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Baseline value within 24 hrs before first treatment and after 80 +/- 14 days(evaluation visit 1)
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Change in tumor metabolic activity
Time Frame: Baseline value within 24 hrs before first treatment and after 214 +/- 14 days (evaluation visit 2)
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Change in hormone levels including chromogranin- A (CgA), chromogranin-B (CgB), neuron specific enolase (NSE) and specific hormones.
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Baseline value within 24 hrs before first treatment and after 214 +/- 14 days (evaluation visit 2)
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Progression-free survival (PFS)
Time Frame: Twelve weeks after 80 days from first treatment (4 treatment cycles) or the corresponding time.
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Number of patients with progression-free survival (PFS).
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Twelve weeks after 80 days from first treatment (4 treatment cycles) or the corresponding time.
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Change in replication profile of AdVince
Time Frame: Before and 4hrs after each treatment cycle up to a time period of 214 days.
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Replication profile determined by quantification of adenovirus genomic copies in patient´s blood by quantitative real-time polymerase chain reaction (QRT-PCR).
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Before and 4hrs after each treatment cycle up to a time period of 214 days.
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Change in replication profile of AdVince
Time Frame: Before and 24hrs after each treatment up to a time period of 214 days.
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Replication profile determined by quantification of adenovirus genomic copies in patient´s blood by quantitative real-time polymerase chain reaction (QRT-PCR).
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Before and 24hrs after each treatment up to a time period of 214 days.
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Change in replication profile of AdVince
Time Frame: Before and 72hrs after each treatment cycle up to a time period of 214 days.
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Replication profile determined by quantification of adenovirus genomic copies in patient´s blood by quantitative real-time polymerase chain reaction (QRT-PCR).
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Before and 72hrs after each treatment cycle up to a time period of 214 days.
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Change in the humoral immune response to AdVince
Time Frame: At baseline, after 8+2 days, after 50 +/- 7days, optional after 124 +/- 7days and 184 +/- 7 days.
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Detection of anti-adenovirus neutralizing antibodies against adenovirus.
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At baseline, after 8+2 days, after 50 +/- 7days, optional after 124 +/- 7days and 184 +/- 7 days.
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Change in the cytokine-mediated immune response
Time Frame: At baseline and at 4hrs following each treatment up to a time period of 214 days.
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Measure from patient´s plasma.
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At baseline and at 4hrs following each treatment up to a time period of 214 days.
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Change in the cytokine-mediated immune response
Time Frame: At baseline and at 24hrs following each treatment up to a time period of 214 days.
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Measure from patient´s plasma.
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At baseline and at 24hrs following each treatment up to a time period of 214 days.
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Change in the cytokine-mediated immune response
Time Frame: At baseline and at 72hrs following each treatment up to a time period of 214 days.
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Measured from patient´s plasma.
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At baseline and at 72hrs following each treatment up to a time period of 214 days.
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Joakim Crona, MD, PhD, Uppsala University Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 1, 2016
Primary Completion (Anticipated)
August 1, 2023
Study Completion (Anticipated)
September 1, 2024
Study Registration Dates
First Submitted
March 11, 2016
First Submitted That Met QC Criteria
April 19, 2016
First Posted (Estimate)
April 22, 2016
Study Record Updates
Last Update Posted (Actual)
November 5, 2021
Last Update Submitted That Met QC Criteria
November 4, 2021
Last Verified
November 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- VIRUSNET201401
- 2014-000614-64 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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