Title

A randomised trial to evaluate the cfDNA Pancreatic Cancer test (Avantect) in the early detection of pancreatic cancer in patients with newly diagnosed diabetes mellitus

Description

The aim of the SAFE-D research study is to evaluate a novel blood test, the Avantect test, to detect clues or biomarkers for the presence of pancreatic cancer in people that have been newly diagnosed with type II diabetes.??

According to the 2021 National Diabetes Audit, about 240,000 patients are diagnosed with diabetes every year in England. Unfortunately, it is known that this particular group of people have up to ten times higher-than-average risk of developing pancreatic cancer. Pancreatic cancer is a cancer that is currently very hard to diagnose in its early stages making it harder to treat successfully. However, if diagnosed early enough, it is possible to prolong survival by removing the cancer with surgery.

There is currently no approved screening test for pancreatic cancer. The Avantect test, developed by ClearNote Health, is a new test designed to detect minute quantities of biomarkers in the blood that will flag the possible presence of pancreatic cancer at a very early treatable stage, before symptoms become apparent. The test is non-invasive and so poses virtually no risk to patients, yet if proven to accurately detect the presence of pancreatic cancer early enough, will have life-changing benefits for thousands of people with newly diagnosed type II diabetes.

The SAFE-D research study will initially recruit 800 participants aged between 50-84 who have been newly diagnosed with type II?diabetes (within 6 months) into a 6-month long Pilot study, before we will roll this into a larger study.

The SAFE-D study is currently in development and will begin recruitment in 2025. In the meantime, if you require any further information please contact the SAFE-D team on safed@soton.ac.uk .

The wealth of information provided by study participants will allow us to determine if the Avantect test can be used as a reliable test to monitor individuals with new onset diabetes in the future, as well as help us understand and treat pancreatic cancer patients better. With this in mind, we are deeply grateful to anyone interested in taking part.

Objectives

Primary:

• To run a six-month Pilot study to evaluate participant recruitment feasibility. The goal here to see if the enrolment strategy is working well and to achieve a conversion rate of greater than 10% of invitation to enrolment to the trial. The aim is to sign up 800 participants in this short pilot study and to fine tune our systems to improve our recruitment rate. Initial analysis of the Avantect test results will be undertaken.
• If the Pilot proves successful, the study will move to two key stages:

1. 1. Study Stage 1: To evaluate how well the Avantect test picks up pancreatic cancer (sensitivity) and how well the Avantect test is able to rule out the presence of pancreatic cancer (specificity). Using our optimised recruitment systems, the study will be expanded significantly to incorporate a second large block of enrolled participants.?
   2. Study Stage 2: To evaluate the proportion of pancreatic cancers deemed resectable across all the patients enrolled and a final analysis of the sensitivity and selectivity of the Avantect test in detecting pancreatic cancer early. When a tumour is resectable, it can be removed by surgery, and patients with resectable pancreatic cancer are typically in the earliest stages of the disease. This final stage of the study will involve another sequential, larger expansion of participant enrolment.

Secondary:

• To evaluate the Avantect test in detecting pancreatic cancer in the entire study cohort (Pilot, study stage 1 and study stage 2 combined), looking specifically at
  • • How well the Avantect test works at being able to predict the presence of pancreatic cancer.? This is a Positive predictive value (PPV), and is worked out by comparing the number of people with one or more Avantect potentially positive, ¡°detected¡± results out of all the people that were tested and actually diagnosed with pancreatic cancer.
    • How well the Avantect test works at being able to predict that no pancreatic cancer is present. This is a Negative predictive value (NPV), measured by the number of people with at least one Avantect ¡°not detected¡± test result, no reported ¡°detected¡± test results, and no diagnosis of pancreatic cancer out of the total number of?people that were tested with no diagnosis of pancreatic cancer.
    • How effective the Avantect test is at picking up biomarkers in the blood to lead to an earlier diagnosis of pancreatic cancer. This is measured by Pancreatic stage shift, which is the proportion of pancreatic cancers diagnosed at stage I/II out of all pancreatic cancers.
    • Actual pancreatic cancer resectability rate. This is the proportion of participants with pancreatic cancer that underwent surgery to remove pancreatic cancer tumours.
• To evaluate the beneficial effect of the Avantect test, over the entire study cohort (Pilot, study stage 1 and study stage 2 combined), looking specifically at:
  • • Overall survival (time-to-event)
    • Time to pancreatic cancer diagnosis relative to new onset diabetes diagnosis
    • Effect on state of anxiety over time
    • Performance characteristics for high-grade neoplasia. This is where cells show abnormal

Trial Design:

Trial Status:

In set-up

Population:

Up to 15,000 male and female participants between the age of 50 ¨C 84 years with newly diagnosed type II diabetes mellitus (within previous six months) across the UK.

Funder:

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This study is primarily funded by ClearNote Health with additional financial support from Cancer Research UK Core funding at the Ìì·¢ÓéÀÖÆåÅÆ_Ìì·¢ÓéÀÖAPP-¹ÙÍø|ÏÂÔØ Clinical Trials Unit.

The University Hospital Ìì·¢ÓéÀÖÆåÅÆ_Ìì·¢ÓéÀÖAPP-¹ÙÍø|ÏÂÔØ NHS Foundation Trust is the research sponsor for this study.