Exploration of Molecular Biomarkers for Lu-177 DOTATATE Therapy in Midgut Neuroendocrine Tumor (GENEBIOLuNET)

April 7, 2025 updated by: University Hospital, Toulouse

Pilot Study for Measuring Molecular Biomarkers and Their Capacity to Characterize Radionuclide Therapy With Lu-177 DOTATATE) in Metastatic G1-G2 Neuroendocrine Midgut Tumors

Midgut neuroendocrine tumours present an increasing incidence and poor survival at 5 years with limited therapeutic options for metastatic, non-operable cases. Lu-177 Dotatate, targeting somatostatin receptors, is an internal vectorized radiotherapy using Lu-177, an ideal radionuclide for peptide radionuclide therapy. In NETTER-1 phase III randomized clinical trial, Lu-177 Dotatate proved its superiority in increasing progression free survival for midgut neuroendocrine tumors. This study hypothesize that finding biomarkers of individual radio sensitivity for this type of internal vectorized therapy would allow treatment personalization. The protocol aim at studying transcript variations induced by this therapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Internal vectorized therapy using Lu-177 Dotatate (abbreviated peptide receptor radionuclide therapy) was recently shown to improve progression free survival and response in metastatic progressive midgut neuroendocrine tumors (NETTER-1 phase III trial).

Lu-177 Dotatate is administered as a series of four consecutive intra veinous injections of an activity of 7.4 gigabequerel every 8 weeks.

In order to identify potential biomarkers of radio sensitivity to Lu-177 Dotatate, investigators aim to study the stability of gene/miRNA transcripts in the absence of Lu-177 Dotatate or at 6 months after treatment as well as the variations in transcript analysis after 2 Lu-177 Dotatate injections and at the end of the treatment.

Transcript variation analysis will be confronted and correlated with peripheral blood pharmacokinetic studies aimed at calculating time activity curves and provide biodosimetry information; other correlations with imaging modalities assessment of dosimetry or disease response to treatment or toxicity effects induced by Lu-177 Dotatate will also be studied.

Study Type

Interventional

Enrollment (Actual)

47

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Toulouse, France, 31059
        • CHU de Toulouse

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients ≥18 years old; histopathologically confirmed grade 1-2 midgut neuroendocrine tumor with documented progression during the year preceding inclusion upon RECIST criteria on computerized tomography, Octreoscan or Ga-68 positron emission tomography/computerized tomography
  • Patients having an indication for Lu-177 Dotatate treatment validated during multidisciplinary meeting coordinated by Pr Rosine Guimbaud under RENATEN coordination;
  • Measurable target lesions upon RECIST criteria
  • Patients on somatostatin analogues treatment. Every somatostatin analogue injection should be organized to be administered 24 to 48 hours after each injection of Lu-177 Dotatate.
  • All patients should be in a clinical state allowing them to continue treatment.
  • Social security affiliation is mandatory.

Exclusion Criteria:

  • Patients on chemotherapy or other targeted therapy within the 4 months preceding peptide receptor radionuclide therapy
  • Fertile patients refusing active contraception ; pregnancy.
  • Patients with prior chemotherapy or peptide receptor radionuclide therapy administration
  • Patients with uncontrollable psychotic disorders
  • Renal hepatic and medullary insufficiency

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Non-drug intervention type

Exploration of gene transcript variation on seriate blood samples before treatment, before and after the 2nd and the 4th Lu-Dotatate injection and before and after the 6 month post treatment follow-up.

Measures of stability and reproducibility of selected gene transcripts and miRNA as radio sensitivity genes or progressive metastatic midgut neuroendocrine tumors genetic signatures before and during Lu-177 Dotatate internal vectorized therapy, as well as on the 6-month follow-up.
Biological: non-drug intervention type
8 peripheral blood samples (8x5ml) will be obtained at different times ; before, during and after treatment
Other Names:
  • Blood samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peptide receptor radionuclide therapy radio-induction variation of radiosensibility/reparation genes
Time Frame: Change from before at during treatment
Variations in gene transcripts will be registered and processed by a bio-informatician
Change from before at during treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of gene transcript variations
Time Frame: during treatment and until 48 hours after treatment
Analysis of gene transcript variation by quantitative real-time polymerase chain reaction
during treatment and until 48 hours after treatment
Evaluation of interindividual variability with NONMEN software
Time Frame: during treatment and until 48 hours after treatment
Analysis of Lu-177 DOTATATE plasma concentration during treatment and 48 hours after treatment
during treatment and until 48 hours after treatment
Evaluation of therapeutic response according to RECIST criteria
Time Frame: 6 months post therapy
Correlation between gene variations and the therapeutic response assessed on RECIST criteria
6 months post therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Toulouse

Investigators

  • Study Chair: Lavinia VIJA, MD, PhD, University Hospital, Toulouse

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2018

Primary Completion (Actual)

May 22, 2024

Study Completion (Actual)

May 22, 2024

Study Registration Dates

First Submitted

July 27, 2018

First Submitted That Met QC Criteria

September 10, 2018

First Posted (Actual)

September 12, 2018

Study Record Updates

Last Update Posted (Actual)

April 10, 2025

Last Update Submitted That Met QC Criteria

April 7, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RC31/17/0356

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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