Biomarker Identification of Radionuclide Therapy-induced Radiation Responses

NCT ID: NCT05513469

Last Updated: 2023-04-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2024-10-01

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.

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.

Conditions

Neuroendocrine Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Peptide receptor radionuclide therapy

PRRT 4x7.4GBq

Group Type: OTHER

Lutathera

Intervention Type: DRUG

regulair PRRT of 4 cycles with 7.4GBq

Interventions

Lutathera

regulair PRRT of 4 cycles with 7.4GBq

Intervention Type: DRUG

Other Intervention Names

177lu-dotatate

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Erasmus Medical Center

OTHER

Sponsor Role: lead

Responsible Party

M.N. Becx

PhD-student / coordinating investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Erasmus MC

Rotterdam, South Holland, Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

M.N. Becx

Role: CONTACT

m.becx@erasmusmc.nl

43449

Facility Contacts

Erasmus N MC

Role: primary

m.becx@erasmusmc.nl

43449

Other Identifiers

80190

Identifier Type: -

Identifier Source: org_study_id