Back to resultsStudy of Recombinant Adenovirus AdVince in Patients With Neuroendocrine Tumors; Safety and Efficacy (RADNET)
Primary Purpose
Neuroendocrine Tumors
Status
Recruiting
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
AdVince
Sponsored by
About this trial
This is an interventional treatment trial for Neuroendocrine Tumors
Eligibility Criteria
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
Sites / Locations
- Endocrine Oncology Clinic, Uppsala University HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
AdVince
Arm 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.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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).
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).
Change in tumor metabolic activity
Change in hormone levels including chromogranin- A (CgA), chromogranin-B (CgB), neuron specific enolase (NSE) and specific hormones.
Change in tumor metabolic activity
Change in hormone levels including chromogranin- A (CgA), chromogranin-B (CgB), neuron specific enolase (NSE) and specific hormones.
Progression-free survival (PFS)
Number of patients with progression-free survival (PFS).
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).
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).
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).
Change in the humoral immune response to AdVince
Detection of anti-adenovirus neutralizing antibodies against adenovirus.
Change in the cytokine-mediated immune response
Measure from patient´s plasma.
Change in the cytokine-mediated immune response
Measure from patient´s plasma.
Change in the cytokine-mediated immune response
Measured from patient´s plasma.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02749331
Brief Title
Study of Recombinant Adenovirus AdVince in Patients With Neuroendocrine Tumors; Safety and Efficacy
Acronym
RADNET
Official Title
Study of Recombinant Adenovirus (AdVince) in Patients With Neuroendocrine Tumors; Safety and Efficacy
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Recruiting
Study Start Date
March 2016 (Actual)
Primary Completion Date
August 2023 (Anticipated)
Study Completion Date
September 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Uppsala University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroendocrine Tumors
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
AdVince
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
AdVince
Other Intervention Name(s)
Ad5PeptideTransductionDomain(PTD)(CgA-E1AmiR122)
Intervention Description
Virus solution for infusion in intrahepatic artery
Primary Outcome Measure Information:
Title
Number of Adverse Events (AE) according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.03
Description
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).
Time Frame
From screening visit and through study completion, an average time of 18 months.
Secondary Outcome Measure Information:
Title
Change in tumor size
Description
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).
Time Frame
Measured within 4 weeks before first treatment and after 80 +/-14 days (evaluation visit 1)
Title
Change in tumor size
Description
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).
Time Frame
Measured within 4 weeks before first treatment and after 214 +/- 14 days (evaluation visit 2)
Title
Change in tumor metabolic activity
Description
Change in hormone levels including chromogranin- A (CgA), chromogranin-B (CgB), neuron specific enolase (NSE) and specific hormones.
Time Frame
Baseline value within 24 hrs before first treatment and after 80 +/- 14 days(evaluation visit 1)
Title
Change in tumor metabolic activity
Description
Change in hormone levels including chromogranin- A (CgA), chromogranin-B (CgB), neuron specific enolase (NSE) and specific hormones.
Time Frame
Baseline value within 24 hrs before first treatment and after 214 +/- 14 days (evaluation visit 2)
Title
Progression-free survival (PFS)
Description
Number of patients with progression-free survival (PFS).
Time Frame
Twelve weeks after 80 days from first treatment (4 treatment cycles) or the corresponding time.
Title
Change in replication profile of AdVince
Description
Replication profile determined by quantification of adenovirus genomic copies in patient´s blood by quantitative real-time polymerase chain reaction (QRT-PCR).
Time Frame
Before and 4hrs after each treatment cycle up to a time period of 214 days.
Title
Change in replication profile of AdVince
Description
Replication profile determined by quantification of adenovirus genomic copies in patient´s blood by quantitative real-time polymerase chain reaction (QRT-PCR).
Time Frame
Before and 24hrs after each treatment up to a time period of 214 days.
Title
Change in replication profile of AdVince
Description
Replication profile determined by quantification of adenovirus genomic copies in patient´s blood by quantitative real-time polymerase chain reaction (QRT-PCR).
Time Frame
Before and 72hrs after each treatment cycle up to a time period of 214 days.
Title
Change in the humoral immune response to AdVince
Description
Detection of anti-adenovirus neutralizing antibodies against adenovirus.
Time Frame
At baseline, after 8+2 days, after 50 +/- 7days, optional after 124 +/- 7days and 184 +/- 7 days.
Title
Change in the cytokine-mediated immune response
Description
Measure from patient´s plasma.
Time Frame
At baseline and at 4hrs following each treatment up to a time period of 214 days.
Title
Change in the cytokine-mediated immune response
Description
Measure from patient´s plasma.
Time Frame
At baseline and at 24hrs following each treatment up to a time period of 214 days.
Title
Change in the cytokine-mediated immune response
Description
Measured from patient´s plasma.
Time Frame
At baseline and at 72hrs following each treatment up to a time period of 214 days.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Magnus Essand, Professor
Phone
+46184714535
Email
magnus.essand@igp.uu.se
First Name & Middle Initial & Last Name or Official Title & Degree
Di Yu, PhD
Phone
+46707204196
Email
di.yu@igp.uu.se
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joakim Crona, MD, PhD
Organizational Affiliation
Uppsala University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Endocrine Oncology Clinic, Uppsala University Hospital
City
Uppsala
ZIP/Postal Code
752 37
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joakim Crona, MD, PhD
Phone
+46186114917
Email
joakim.crona@medsci.uu.se
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of Recombinant Adenovirus AdVince in Patients With Neuroendocrine Tumors; Safety and Efficacy
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