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

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ClinicalTrials.gov Identifier: NCT02749331
Recruitment Status : Recruiting
First Posted : April 22, 2016
Last Update Posted : October 4, 2018
Sponsor:
Information provided by (Responsible Party):
Uppsala University

Tracking Information
First Submitted Date  ICMJE March 11, 2016
First Posted Date  ICMJE April 22, 2016
Last Update Posted Date October 4, 2018
Actual Study Start Date  ICMJE March 2016
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 19, 2016)
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. ]
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02749331 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 19, 2016)
  • Change in tumor size [ Time Frame: Measured within 4 weeks before first treatment and after 80 +/-14 days (evaluation visit 1) ]
    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 [ Time Frame: Measured within 4 weeks before first treatment and after 214 +/- 14 days (evaluation visit 2) ]
    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 [ Time Frame: Baseline value within 24 hrs before first treatment and after 80 +/- 14 days(evaluation visit 1) ]
    Change in hormone levels including chromogranin- A (CgA), chromogranin-B (CgB), neuron specific enolase (NSE) and specific hormones.
  • Change in tumor metabolic activity [ Time Frame: Baseline value within 24 hrs before first treatment and after 214 +/- 14 days (evaluation visit 2) ]
    Change in hormone levels including chromogranin- A (CgA), chromogranin-B (CgB), neuron specific enolase (NSE) and specific hormones.
  • Progression-free survival (PFS) [ Time Frame: Twelve weeks after 80 days from first treatment (4 treatment cycles) or the corresponding time. ]
    Number of patients with progression-free survival (PFS).
  • Change in replication profile of AdVince [ Time Frame: Before and 4hrs after each treatment cycle up to a time period of 214 days. ]
    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 [ Time Frame: Before and 24hrs after each treatment up to a time period of 214 days. ]
    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 [ Time Frame: Before and 72hrs after each treatment cycle up to a time period of 214 days. ]
    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 [ Time Frame: At baseline, after 8+2 days, after 50 +/- 7days, optional after 124 +/- 7days and 184 +/- 7 days. ]
    Detection of anti-adenovirus neutralizing antibodies against adenovirus.
  • 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. ]
    Measure from patient´s plasma.
  • 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. ]
    Measure from patient´s plasma.
  • 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. ]
    Measured from patient´s plasma.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Recombinant Adenovirus AdVince in Patients With Neuroendocrine Tumors; Safety and Efficacy
Official Title  ICMJE Study of Recombinant Adenovirus (AdVince) in Patients With Neuroendocrine Tumors; Safety and Efficacy
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neuroendocrine Tumors
Intervention  ICMJE Drug: AdVince
Virus solution for infusion in intrahepatic artery
Other Name: Ad5PeptideTransductionDomain(PTD)(CgA-E1AmiR122)
Study Arms  ICMJE Experimental: AdVince

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.

Intervention: Drug: AdVince
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 19, 2016)
35
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Magnus Essand, Professor +46184714535 magnus.essand@igp.uu.se
Contact: Justyna Leja-Jarblad, PhD +46184714524 justyna.leja-jarblad@igp.uu.se
Listed Location Countries  ICMJE Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02749331
Other Study ID Numbers  ICMJE VIRUSNET201401
2014-000614-64 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Uppsala University
Study Sponsor  ICMJE Uppsala University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Kjell Öberg, MD,Professor Uppsala University Hospital
PRS Account Uppsala University
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP