Ignite Creation Date:
2025-12-24 @ 10:52 PM
Ignite Modification Date:
2026-01-01 @ 4:26 PM
Study NCT ID:
NCT05513469
Status:
UNKNOWN
Last Update Posted:
2023-04-07
First Post:
2022-08-11
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Biomarker Identification of Radionuclide Therapy-induced Radiation Responses
Sponsor:
Erasmus Medical Center
Organization:
Study Overview
Official Title:
Biomarker Identification of Radionuclide Therapy-induced Radiation Responses
Status:
UNKNOWN
Status Verified Date:
2023-04
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Radio-Marker
Brief Summary:
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.
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.
Detailed Description:
Altogether, the PBMC and ctDNA analyses will provide essential information on the PRRT radiation response using blood as easily accessible material. Future research can focus on development of radiation response biomarkers based on the outcomes of this study.
Objective: This is a pilot study to validate the possibility of determining the radiation response of PRRT with 177Lu-DOTATATE in PBMCs and ctDNA.
Study design: Prospective translational study with additional blood collections at 4 timepoints during regular patient care for ex vivo characterisation.
Study population: Twenty patients with locally advanced or metastatic NET receiving the first PRRT cycle of 7.4 GBq 177Lu-DOTATATE.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Participants who receive standard PRRT will undergo 4 additional venipunctures during their scheduled stay in the hospital for PRRT administration. The burden of the venipunctures is minimal. There is no benefit for particitants.
Objective: This is a pilot study to validate the possibility of determining the radiation response of PRRT with 177Lu-DOTATATE in PBMCs and ctDNA.
Study design: Prospective translational study with additional blood collections at 4 timepoints during regular patient care for ex vivo characterisation.
Study population: Twenty patients with locally advanced or metastatic NET receiving the first PRRT cycle of 7.4 GBq 177Lu-DOTATATE.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Participants who receive standard PRRT will undergo 4 additional venipunctures during their scheduled stay in the hospital for PRRT administration. The burden of the venipunctures is minimal. There is no benefit for particitants.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: