Back to resultsExploration of Molecular Biomarkers for Lu-177 DOTATATE Therapy in Midgut Neuroendocrine Tumor (GENEBIOLuNET)
Primary Purpose
Midgut Neuroendocrine Tumors
Status
Active
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
non-drug intervention type
Sponsored by
About this trial
This is an interventional diagnostic trial for Midgut Neuroendocrine Tumors focused on measuring Lu-177 Dotatate, transcript analysis and variation, molecular biomarkers, midgut neuroendocrine tumors
Eligibility Criteria
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
Sites / Locations
- CHU de Toulouse
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Non-drug intervention type
Arm Description
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.
Outcomes
Primary Outcome Measures
Peptide receptor radionuclide therapy radio-induction variation of radiosensibility/reparation genes
Variations in gene transcripts will be registered and processed by a bio-informatician
Secondary Outcome Measures
Evaluation of gene transcript variations
Analysis of gene transcript variation by quantitative real-time polymerase chain reaction
Evaluation of interindividual variability with NONMEN software
Analysis of Lu-177 DOTATATE plasma concentration during treatment and 48 hours after treatment
Evaluation of therapeutic response according to RECIST criteria
Correlation between gene variations and the therapeutic response assessed on RECIST criteria
Full Information
NCT ID
NCT03667092
First Posted
July 27, 2018
Last Updated
September 18, 2023
Sponsor
University Hospital, Toulouse
1. Study Identification
Unique Protocol Identification Number
NCT03667092
Brief Title
Exploration of Molecular Biomarkers for Lu-177 DOTATATE Therapy in Midgut Neuroendocrine Tumor
Acronym
GENEBIOLuNET
Official Title
Pilot Study for Measuring Molecular Biomarkers and Their Capacity to Characterize Radionuclide Therapy With Lu-177 DOTATATE) in Metastatic G1-G2 Neuroendocrine Midgut Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 1, 2018 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Toulouse
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Midgut Neuroendocrine Tumors
Keywords
Lu-177 Dotatate, transcript analysis and variation, molecular biomarkers, midgut neuroendocrine tumors
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Non-drug intervention type
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
non-drug intervention type
Other Intervention Name(s)
Blood samples
Intervention Description
8 peripheral blood samples (8x5ml) will be obtained at different times ; before, during and after treatment
Primary Outcome Measure Information:
Title
Peptide receptor radionuclide therapy radio-induction variation of radiosensibility/reparation genes
Description
Variations in gene transcripts will be registered and processed by a bio-informatician
Time Frame
Change from before at during treatment
Secondary Outcome Measure Information:
Title
Evaluation of gene transcript variations
Description
Analysis of gene transcript variation by quantitative real-time polymerase chain reaction
Time Frame
during treatment and until 48 hours after treatment
Title
Evaluation of interindividual variability with NONMEN software
Description
Analysis of Lu-177 DOTATATE plasma concentration during treatment and 48 hours after treatment
Time Frame
during treatment and until 48 hours after treatment
Title
Evaluation of therapeutic response according to RECIST criteria
Description
Correlation between gene variations and the therapeutic response assessed on RECIST criteria
Time Frame
6 months post therapy
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lavinia VIJA, MD, PhD
Organizational Affiliation
University Hospital, Toulouse
Official's Role
Study Chair
Facility Information:
Facility Name
CHU de Toulouse
City
Toulouse
ZIP/Postal Code
31059
Country
France
12. IPD Sharing Statement
Learn more about this trial
Exploration of Molecular Biomarkers for Lu-177 DOTATATE Therapy in Midgut Neuroendocrine Tumor
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