NCT05513469: Radio-Marker

Biomarker Identification of Radionuclide Therapy-induced Radiation Responses

Status unknown NA Last updated 7 April 2023

What this trial tests

NA trial testing Lutathera in Neuroendocrine Tumors in 20 participants. Status unknown.

Timeline

1 January 2023

Primary endpoint
1 October 2024

1 October 2024

Quick facts

Lead sponsor	Erasmus Medical Center
Phase	NA
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	basic science
Enrollment	20
Start date	1 January 2023
Primary completion	1 October 2024
Estimated completion	1 October 2024
Sites	1 location across Netherlands

Drugs / interventions tested

• Lutathera (lutetium (177Lu) oxodotreotide) — full drug profile →

Conditions studied

• Neuroendocrine Tumors — all drugs for Neuroendocrine Tumors →

Sponsor

Erasmus Medical Center

Who can join

Adults 18 to 100, any sex, with Neuroendocrine Tumors. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Peptide receptor radionuclide therapy (PRRT) with \[177Lu\]Lu-DOTA-\[Tyr3\]octreotate (177Lu-DOTATATE) is a form of internal radiation treatment for patients with neuroendocrine tumors (NET) to reduce tumor growth and stabilize disease. Due to limited response rates, there is a need to improve this therapy. A better understanding of therapeutic radiobiological responses, such as transcriptional and DNA damage responses, could contribute to identification of biomarkers for toxicity and/or efficacy prediction. Easy access to biological samples for biomarker discovery would be via a so-called liquid biopsy (drawing blood) to collect healthy peripheral blood mononuclear cells (PBMCs) or circulating tumor DNA (ctDNA) for further investigation.

Exposure to ionizing radiation (IR) such as by PRRT leads to complex cellular responses including activation of the DNA damage response and changes in gene expression which can differ between individuals. This was previously shown for ex vivo external beam radiation of blood cells in which radiation responsive genes were identified. These genes were also similarly up- or downregulated following in vivo exposure to total-body irradiation of patients. In addition, different studies have shown a good correlation between radiation dose to the blood and DNA double strand break induction in PBMCs for various PRRT-like treatments. These results show that such events can be measured in PBMCs and indicate that ex vivo irradiation can mimic the in vivo transcriptional regulation and DNA damage induction. Therefore, to identify PRRT-induced cellular responses, the investigators will analyze the effects of 177Lu-DOTATATE IR on the transcriptional regulation in PBMCs and compare this regulation to radiation dose and DNA damage induction.

In addition, it was shown that levels of ctDNA can be associated with treatment response and anticancer treatment is also shown to influence ctDNA methylation patterns. The investigators will therefore explore dynamics of ctDNA levels and methylation patterns before and after PRRT to provide more knowledge of the effect of radiation response on ctDNA.

This is a pilot study to validate the possibility of determining the radiation response of PRRT with 177Lu-DOTATATE in PBMCs and ctDNA.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Peptide Receptor Radionuclide Therapy (PRRT): Innovations and Improvements.
   Merola E, Grana CM. · · 2023 · cited 19× · PMID 37296936 · DOI 10.3390/cancers15112975