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Human Adenovirus C Serotype 5 With E1 Gene Controlled By Chromogranin A Promoter And Hexon Modified With Protein Transduction Domain Motif

In the realm of cancer research, a groundbreaking clinical trial is underway to evaluate the safety and efficacy of AdVince, a genetically modified adenovirus designed to target metastatic neuroendocrine tumors (NETs). This innovative approach offers hope for patients with advanced-stage NETs, a group of cancers that often prove challenging to treat. The RADNET study aims to assess the potential of AdVince as a new treatment option for those who have exhausted standard therapies.

Table of Contents

What is AdVince?

AdVince is an innovative medical treatment being developed for patients with metastatic neuroendocrine tumors. It is a type of genetically modified adenovirus, specifically designed to target and treat these challenging cancers.[1]

The full scientific name of AdVince is quite complex: HUMAN ADENOVIRUS C SEROTYPE 5 WITH E1 GENE CONTROLLED BY CHROMOGRANIN A PROMOTER AND HEXON MODIFIED WITH PROTEIN TRANSDUCTION DOMAIN MOTIF. It’s also known by other names such as Ad5PTD(CgA-E1AmiR122).[1]

What condition does AdVince target?

AdVince is being developed to treat neuroendocrine neoplasms (NENs). These are a diverse group of tumors that can occur in various organs, most commonly in the digestive system and lungs. NENs are characterized by:[1]

  • Varying symptoms and tumor biology
  • Often diagnosed at an advanced stage
  • Poor prognosis (65% of patients die within 5 years)
  • Limited treatment options, especially for metastatic disease

While surgery can be curative for early-stage NENs, more than half of the patients have metastatic disease at diagnosis, for which there is currently no cure.[1]

How does AdVince work?

AdVince is a genetically modified adenovirus. Adenoviruses are common viruses that usually cause mild illnesses like colds. However, in this case, the virus has been altered to specifically target and kill neuroendocrine tumor cells.[1]

The modifications to the virus include:

  • The E1 gene is controlled by a chromogranin A promoter. Chromogranin A is a protein often produced by neuroendocrine tumors, so this modification helps the virus target these specific cancer cells.
  • The hexon (a part of the virus’s structure) is modified with a protein transduction domain motif. This change may help the virus enter tumor cells more effectively.

Current Clinical Trial

AdVince is currently being studied in a clinical trial called RADNET (Recombinant Adenovirus in Neuroendocrine Tumors). The main goals of this trial are:[1]

  1. To evaluate the safety of repeated infusions of AdVince into the hepatic artery (the main blood vessel supplying the liver) in patients with metastatic NENs
  2. If possible, to determine the maximum tolerated dose (MTD)
  3. To assess the anti-tumor effectiveness of AdVince infusions on metastatic neuroendocrine tumors
  4. To study how the virus replicates in the body
  5. To examine the body’s immune response to AdVince

Who is eligible for the trial?

The trial has specific criteria for who can participate. Some key eligibility factors include:[1]

  • Adults (18 years or older) with confirmed neuroendocrine tumors of gastrointestinal, pancreatic, or bronchial origin
  • Disease that has progressed in the last 6 months and is not suitable for surgery
  • Patients who have exhausted standard treatment options
  • Liver-dominant disease, but with less than 60% of the liver affected
  • Relatively good overall health (Karnofsky performance status of 70% or higher)

There are also several factors that would exclude a person from participating, such as certain liver conditions, recent other cancer treatments, or active infections.[1]

How is AdVince administered?

AdVince is given as a solution for injection directly into the hepatic artery, which is the main blood vessel supplying the liver. This method of administration is called intrahepatic use.[1]

The treatment is given in cycles, with patients receiving multiple injections over a period of time. The exact dosing schedule and amount are part of what’s being studied in the current clinical trial.[1]

Safety and Efficacy Evaluation

The RADNET trial is closely monitoring the safety and effectiveness of AdVince. This includes:[1]

  • Tracking any side effects or adverse events
  • Monitoring changes in laboratory tests and vital signs
  • Assessing tumor size and activity using imaging techniques like CT, PET, or MRI scans
  • Measuring hormone levels and other biological markers
  • Evaluating how long patients live without their disease progressing (progression-free survival)
  • Studying how the virus replicates in the body and how the immune system responds to it

It’s important to note that AdVince is still in the experimental stage. While it shows promise, more research is needed to fully understand its safety and effectiveness in treating neuroendocrine tumors.[1]

Aspect Details
Study Name RADNET (Study of Recombinant Adenovirus AdVince in Patients With Neuroendocrine Neoplasms; Safety and Efficacy)
Treatment AdVince (genetically modified adenovirus)
Target Condition Metastatic neuroendocrine neoplasms (NENs)
Administration Method Repeated infusions into the hepatic artery
Primary Objectives Evaluate safety, determine maximum tolerated dose
Secondary Objectives Assess anti-tumor efficacy, viral replication, immune responses
Key Eligibility Criteria Adults with confirmed NENs, disease progression, exhausted standard treatments
Main Exclusion Criteria Chronic liver dysfunction, recent viral infections, immunosuppression
Primary Endpoints Adverse events, dose-limiting toxicity, changes in safety parameters
Secondary Endpoints Tumor size/activity, viral replication, immune responses

FAQ

  • What is AdVince and how does it work? AdVince is a genetically modified adenovirus designed to target neuroendocrine tumors. It works by selectively replicating in tumor cells, potentially destroying them while sparing healthy tissue. The virus has been engineered with specific modifications to enhance its effectiveness against NETs.
  • Who is eligible for the AdVince clinical trial? Eligible participants are adults (18 years or older) with histologically confirmed neuroendocrine tumors of gastrointestinal, pancreatic, or bronchial origin. They must have progressing disease that is not suitable for curative surgery and have exhausted standard treatment options. Specific health criteria, such as adequate liver function and performance status, must also be met.
  • How is AdVince administered in the trial? AdVince is administered through repeated infusions into the hepatic artery. This method allows the treatment to be delivered directly to the liver, where many neuroendocrine tumors metastasize.
  • What are the main objectives of the RADNET study? The primary objective is to evaluate the safety of repeated AdVince infusions and determine the maximum tolerated dose if possible. Secondary objectives include assessing the anti-tumor efficacy, determining the virus's replication profile, and measuring immune responses to the treatment.
  • What potential side effects are being monitored in the trial? The study closely monitors for adverse events related to the treatment. This includes checking for local injuries caused by the administration procedure and changes in laboratory parameters, biological markers, and vital signs. The trial also aims to identify any dose-limiting toxicities that may occur.

Ongoing Clinical Trials on Human Adenovirus C Serotype 5 With E1 Gene Controlled By Chromogranin A Promoter And Hexon Modified With Protein Transduction Domain Motif

  • Study of AdVince (Modified Adenovirus) Treatment Through Hepatic Artery Injection in Patients with Advanced Neuroendocrine Neoplasms

    Not recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Sweden

Glossary

  • Neuroendocrine neoplasms (NENs): A diverse group of tumors that arise from cells of the neuroendocrine system. These tumors can occur in various organs, most commonly in the digestive system and lungs.
  • Metastatic: Cancer that has spread from its original site to other parts of the body.
  • Adenovirus: A type of virus that can cause respiratory illnesses in humans. In this context, it has been modified for use as a potential cancer treatment.
  • Hepatic artery: The main blood vessel that supplies oxygenated blood to the liver.
  • Maximum tolerated dose (MTD): The highest dose of a drug or treatment that does not cause unacceptable side effects.
  • Progression-free survival (PFS): The length of time during and after treatment that a patient lives with the disease without it getting worse.
  • Dose-limiting toxicity (DLT): Side effects severe enough to prevent an increase in the dose of a drug or treatment.
  • Karnofsky performance status: A scale used to measure a patient's general well-being and activities of daily life.
  • Humoral response: Part of the immune response that involves antibodies produced by B cells.
  • Cytokine: Small proteins important in cell signaling, particularly in immune responses.

References

  1. http://clinicaltrials.eu/trial/study-on-the-safety-of-advince-for-patients-with-metastatic-neuroendocrine-tumors/