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Trial Title:
Biomarker Identification of Radionuclide Therapy-induced Radiation Responses
NCT ID:
NCT05513469
Condition:
Neuroendocrine Tumors
Conditions: Official terms:
Neuroendocrine Tumors
Lutetium Lu 177 dotatate
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Basic Science
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Lutathera
Description:
regulair PRRT of 4 cycles with 7.4GBq
Arm group label:
Peptide receptor radionuclide therapy
Other name:
177lu-dotatate
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.
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patient with an advanced, well-differentiated midgut neuroendocrine tumor.
- Indication for treatment with PRRT with 7.4 GBq 177Lu-DOTATATE as determined by the
multidisciplinary team.
- Age ≥ 18 years.
Exclusion Criteria:
- Failure to obtain informed consent.
- Patient received IR for imaging purposes within one week prior to PRRT or IR for
therapeutic purposes within 3 months prior to PRRT.
- Previous treatment with PRRT.
- Indication to receive another activity of PRRT than 7.4 GBq.
Gender:
All
Minimum age:
18 Years
Maximum age:
100 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Erasmus MC
Address:
City:
Rotterdam
Zip:
3015 GD
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Erasmus N MC
Phone:
43449
Email:
m.becx@erasmusmc.nl
Start date:
January 1, 2023
Completion date:
October 1, 2024
Lead sponsor:
Agency:
Erasmus Medical Center
Agency class:
Other
Source:
Erasmus Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05513469