NCT03815942

VAccination in Early and ADvanced Prostate caNCEr

Phase I/II Open Label Non-randomised Safety and Efficacy Study of the Viral Vectored ChAd-MVA 5T4 Vaccine in Combination With PD-1 Checkpoint Blockade in Low- or Intermediate-risk Localized or Locally Advanced Prostate Cancer and Advanced Metastatic Prostate Cancer

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: University of Oxford · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a clinical trial of a new treatment for prostate cancer that is a type of vaccine that could be a new way to treat cancer. A vaccine that could alert the immune system to the presence of cancer cells in the body may enable the immune system to target and kill those cells effectively. This vaccine is intended to work by making the immune system kill cells that have a special protein (called 5T4) that is present on the surface of cancer cells. The vaccine is made up of two recombinant viruses ("ChAdOx1"- chimpanzee adenovirus Ox1 and "MVA" - modified vaccinia Ankara) that have been designed to produce the 5T4 protein and have been modified so that they are weakened and cannot reproduce themselves within the body like normal viruses. Once injected into the body, these viruses make the 5T4 protein and help the body's immune system to learn to target this protein and destroy cancer cells. This vaccine will be used in combination with the immunotherapy drug called nivolumab which is an anti-PD-1 (Programmed Death protein-1) monoclonal antibody. This is a molecule that releases the brakes on the immune system and helps the immune system to kill cancer cells more efficiently. Nivolumab as a monotherapy was approved for treatment of several tumour types but not for the prostate cancer. This study will evaluate the safety and efficacy of ChAdOx1-MVA 5T4 vaccine in combination with nivolumab in low and intermediate risk prostate cancer patients who have elected to have their prostate removed and in patients with advanced metastatic prostate cancer.

Detailed description

The purpose of this study was to evaluate the safety and efficacy of a combination of two new vaccines (ChAdOx1.5T4 and MVA.5T4) with a monoclonal antibody (PD-1 mAb, also known as Nivolumab and Opdivo®) against Prostate Cancer. A vaccine that alerts the immune system to the presence of cancer cells in the body may enable the immune system to target and kill those cells effectively. This vaccine is intended to work by making the immune system kill cells that have a special protein (called 5T4) that is present on the surface of cancer cells. The use of two different forms of the vaccine has been shown to generate a more effective immune response. ChAdOx1.5T4 consists of a virus (ChAdOx1), which is a weakened version of a chimpanzee adenovirus that has been genetically altered so that it is impossible for it to grow in humans. Modified Vaccinia virus Ankara (MVA) is licensed as third-generation vaccine against smallpox and serves as a potent vector system for development of new candidate vaccines against infectious diseases and cancer. To both viruses we have added genes that make the 5T4 protein that is present in prostate cancer cells and which is essential to the cancer. By vaccinating, we are hoping to make the body recognise and develop an immune response to these proteins that will neutralise the effects of the cancer in human cells and therefore prevent the infection responsible for the disease. Nivolumab (PD-1 mAb) is an immune checkpoint inhibitor. Immune checkpoints are a normal part of the immune system. Their role is to prevent an immune response from being so strong that it destroys healthy cells in the body. Immune checkpoints engage when proteins on the surface of immune cells called T cells recognize and bind to partner proteins on other cells, such as some tumour cells. These proteins are called immune checkpoint proteins. When the checkpoint and partner proteins bind together, they send an "off" signal to the T cells. This can prevent the immune system from destroying the cancer. Immunotherapy drugs called immune checkpoint inhibitors work by blocking checkpoint proteins from binding with their partner proteins. This prevents the "off" signal from being sent, allowing the T cells to kill the cancer cells. Nivolumab as a monotherapy has been approved for treatment of several tumour types but not currently for prostate cancer. The intent was to have two cohorts of participants: Group 1 were patients who had been diagnosed with low- or intermediate-risk non-metastatic prostate adenocarcinoma and who were scheduled for radical prostatectomy; Group 2 comprised patients with metastatic castration resistant prostate cancer (mCRPC) with evidence of progression on anti-androgens. Unfortunately, it proved impossible to recruit participants into Group 1, so the trial proceeded with just Group 2. It was planned that the results would be measured by a composite response rate defined as one of the following: * reduction of circulating tumour DNA of ≥50% * serum PSA decrease of ≥50% However, the analysis to measure the circulating tumour DNA (ctDNA) was not done for any of the participants due to the trial ending prematurely because of the COVID-19 pandemic in 2020. The trial and the follow-up of participants was severely hampered by the Covid-19 pandemic. In this study, we have shown that the candidate 5TA vaccines given were safe and well-tolerated. No serious adverse reactions occurred during the follow-up period. Most adverse events reported were mild or moderate in severity and all resolved spontaneously. The profile of adverse events reported in this trial is similar to other ChAdOx1 vectored vaccines.

Conditions

• Intermediate Risk Prostate Cancer
• Castration-resistant Prostate Cancer

Interventions

Type	Name	Description
BIOLOGICAL	ChAdOx1-MVA 5T4 vaccine	ChAdOx1.5T4 will be administered intramuscularly in an extremity (e.g. thigh) at a dose of 2.5 x10\^10 virus particles followed by MVA.5T4 administered via the same route at the dose of 2x10\^8 plaque forming units
DRUG	Nivolumab Infusion [Opdivo]	Nivolumab is to be administered as a flat dose of 480 mg over approximately 60-minutes via IV infusion

Timeline

• Start date: 2018-12-10
• Primary completion: 2020-06-24
• Completion: 2020-06-24
• First posted: 2019-01-24
• Last updated: 2025-06-25
• Results posted: 2025-06-25

Locations

2 sites across 1 country: United Kingdom