09Jan 2022 by Ronny Allan No Comments

Ronny Allan

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

Whenever I post about a new 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. Please bear that in mind when reading studies/clinical trials posted on RonnyAllan.NET

What is the aim of this clinical trial?

The aim of this single location trial in Imperial College London is to determine whether pre-treatment with ASTX727 results in re-expression of SSTR2 in patients with metastatic NETs, using 68Ga-DOTA-TATE to image epigenetic modification of the SSTR2 locus allowing subsequent treatment with Lutathera(i.e. PRRT). Patients entered into the study will receive ASTX727 orally up to 3 to 8 days prior to receiving Lutathera treatment.

What is ASTX727?

Oral Decitabine and Cedazuridine (ASTX727) is a DNA methyltransferase (DNMT) inhibitor currently being used in a trial to facilitate oral treatment of certain drugs for adults with intermediate and high-risk myelodysplastic syndromes (MDS) including chronic myelomonocytic leukemia (CMML).

This is extremely technical, but from a study conducted by scientists at Imperial College London, they acknowledged that significant number of patients were unsuitable for (177Lu)DOTATATE due to limited SSTR2 expression. In both in vitro and in vivo treatment of NET cell lines with decitabine not only resulted in re-expression of SSTR2 but importantly, also resulted in enhanced uptake of radiolabeled SSAs, showing functionality in receptor re-expression, a concept that was independently corroborated. The clinical trial would appear to be an extension of this concept for trial in humans who will receive ASTX727 to enhance SSTR2 expression, followed by PRRT, in which (68Ga) DOTA-PET is used to assess SSTR2 re-expression. Utilizing epigenetic modifiers to allow the re-expression of a receptor of interest has the potential to improve the clinical outcome in a significant number of GEP-NET patients who would otherwise not be suitable for PRRT (citation below).

Citation: Sharma, R.; Lythgoe, M.P.; Slaich, B.; Patel, N. Exploring the Epigenome in Gastroenteropancreatic Neuroendocrine Neoplasias. Cancers 2021, 13, 4181. https://doi.org/10.3390/cancers13164181

Further Reading

1. See the clinical trial document “Lutathera and ASTX727 in Neuroendocrine Tumours (LANTana)”
– click here

Note: Always useful to check the inclusion and exclusion criteria in clinical trial documents. Amongst others, I think the key ones that might be on people’s minds are – prior PRRT not accepted, only for well-differentiated NETs less than Ki6755%, tumoural uptake on [68Ga]-DOTA-TATE greater than background liver. There are many more.

2. Somatostatin Receptor Primer – click here (or on the picture)

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.

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