LANTANA
Research type
Research Study
Full title
LANTana: Lutathera and ASTX727 in Neuroendocrine Tumours. Epigenetic modification of somatostatin receptor-2 to improve therapeutic outcome with Lutathera in patients with metastatic neuroendocrine tumours
IRAS ID
285903
Contact name
Rohini Sharma
Contact email
Sponsor organisation
Imperial College London
Eudract number
2020-003800-15
Clinicaltrials.gov Identifier
Duration of Study in the UK
4 years, 3 months, 28 days
Research summary
This is an open label, single arm phase Ib study to evaluate the effect of pre-treatment with ASTX727 followed by Lutathera in 27 patients with progressive, metastatic neuroendocrine tumours (NETs).
ASTX727 is a fixed dose combination of cedazuridine and decitabine, found to increase the systemic exposure of decitabine in the body. Decitabine is a nucleoside hypomethylating agent (HMA) that induces demethylation (removal of a methyl molecule) by blocking the action of DNA methyltransferase, a protein in the body whose job is to add methyl groups. This action prevents cell replication and the proliferation of cancer cells. However, when given on its own, decitabine is rapidly broken down by a protein in the body called CDA (cytidine deaminase). Cedazuridine was therefore added to block CDA so more decitabine is present in the blood to cause the desired effect. As a gene modifier, decitabine has also been found to cause an up-regulation of the receptor SSTR2 on neuroendocrine tumours to allow for SSTR2-targeted radiopeptide therapy.
Lutathera is a synthetic somatostatin analogue (SSA) bound to a radioactive isotope and is a form of Peptide Receptor Radionuclide Therapy (PRRT). When administered to a patient, lutathera binds to SSTR2 and the complex formed is internalised by the cancer cell. As the radioactive isotope decays it emits radiation killing the cell it is inside as well as the nearby surrounding cancer cells. Lutathera therefore delivers direct radiotherapy to a tumour, reducing the unwanted side effects produced when radiation hits healthy cells.Eligible patients on the trial will take ASTX727 for 5 days, be assessed on PET scan for SSTR2 expression on day 8 before taking another 5 days of the drug from day 28+2 and be administered lutathera on day 38+2. This regime will continue every 2 months until lutathera has been given four times.
REC name
Yorkshire & The Humber - Leeds West Research Ethics Committee
REC reference
21/YH/0247
Date of REC Opinion
3 Nov 2021
REC opinion
Further Information Favourable Opinion