16Mar 2023 by Ronny Allan No Comments

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Ronny Allan

Award winning Neuroendocrine Cancer Patient Advocate. Diagnosed with Metastatic Neuroendocrine Cancer in 2010.

Gastric NETs

When I wrote my post entitled “Spotlight on Gastric Neuroendocrine Neoplasms“, I explained what these were with some emphasis on the association with hypergastrinemia (elevated fasting serum gastrin levels) with Type 1 and 2 gNETs being differentiated by the settings in which this occurs. This oversecretion is not the same as so called carcinoid syndrome found in other gastrointestinal NETs. Many people with a Gastric NET will already have acid reflux related issues and many will be taking medications such as proton pump inhibitors. But I was surprised to find there was not an approved targeted medication that aims to decrease gastrin levels. It’s true to say that somatostatin analogues (SSA) inhibit the secretion of many NET associated hormones including gastrin but SSAs are not routinely prescribed for localised Type I gNETs. However, I did find a useful clinical trial which is in progress albeit halted at phase 2 awaiting a larger phase 3 trial.

In the above spotlight, I also wrote about how the stomach works in all of us. When we eat food, G cells release gastrin into the bloodstream. Gastrin stimulates gastrin receptors (also called CCK₂ receptors, CCK₂ R) on enterochromaffin-like (ECL) cells in the stomach lining. The problem is some gNETs is the oversecretion caused in various settings.

The experiemental drug known as Netazepide is a gastrin/CCK₂ receptor antagonist which has recently been identified as a potential novel treatment for hypergastrinemia-associated conditions, with evidence from non-clinical models as well as clinical studies in healthy volunteers. It’s currently focused on Type 1 gNETs and not only claims to decrease oversecretion of Gastrin but in doing so reduces tumour burden over time.

Clinical Trials

There have been several studies of Netazepide in gNETs and other gastric related conditions. In terms of gNETs, the conclusions of the latest one said:

In CAG patients with g-NETs, netazepide once daily by mouth:

can eradicate all tumours, if patients are dosed long enough;
must be given continuously otherwise tumours regrow;
reduces expression of biomarkers CgA and miR-222 in blood, and modulates the expression of several genes in the gastric mucosa, including increasing expression of claudin 10;
can be monitored by measuring biomarkers CgA and miR-222 in blood, avoiding the need for regular gastroscopy;
is a novel targeted medical treatment, and an alternative to surgical removal of the tumours;
is safe and well tolerated; and
merits a multicentre, placebo-controlled trial.

In summary, netazepide can eradicate all g-NETs if patients are dosed for long enough. More importantly, the normalisation of gene expression, in particular the increase in claudin 10 in cells in the gastric mucosa, and normalisation of biomarkers CgA and miR-222 in blood probably reduce the potential of cells to metastasise and to develop into gastric cancer. That benefit starts long before the tumours are eradicated.

According to the manufacturer (Trio Medicines), they plan to do a multicentre, randomised study of netazepide and placebo (ratio 6:1) in 210 patients with Chronic Atrophic Gastritis (CAG) and multiple g-NETs in Europe, USA, and possibly China and Japan. Centres of Excellence of the European and North American Neuroendocrine Tumour Societies (ENETS and NANETS, respectively) have agreed to participate.

The European Medicines Agency has approved in principle a single pivotal study. An IND is in place, and an FDA end-of-phase 2 meeting is planned. To date there is no phase 3 clinical trial listed on the main site (Clinical Trials NIH) (possibly delayed by Covid-19). But I’m now monitoring. I emailed Trio Medicines for info but no reply was received.

Disclaimer

I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me. Neither should any post or comment made by a follower or member of my private group be assumed to be medical advice, even if that person is a healthcare professional as they are not members of the private group or followers of my sites in any official capacity. Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.

Click here to enter Ronny's Clinical Trials Archive

General Clinical Trials Disclaimer

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided in the clinical trials document. It’s very important to check the trial inclusion and exclusion criteria before making any contact. If you need questions, the articles here is very useful Questions to Ask About Clinical Trials | Cancer.Net

The inclusion of any trial within this blog should not be taken as a recommendation by Ronny Allan.

Finally

Whenever I post about a trial or study, some people get excited without understanding that these new treatments and capabilities can very often take years to come to fruition and it’s also possible that clinical trials can be halted, or that national approval agencies will not approve the final product. Plus, not everyone will be eligible, so always check the exclusion and inclusion criteria in the relevant clinical trials document. Please bear that in mind when reading studies/clinical trials posted on RonnyAllan.NET