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

Midgut Neuroendocrine Tumors Clinical Trial

— 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03667092
• Other study ID #: RC31/17/0356
• Status: Active, not recruiting
• Phase: N/A
• Start date: September 1, 2018
• Est. completion date: December 2025

Study information

• Verified date: September 2023
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 47
• Est. completion date: December 2025
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Midgut Neuroendocrine Tumors
• Neuroendocrine Tumors

Intervention

Biological:
• non-drug intervention type
8 peripheral blood samples (8x5ml) will be obtained at different times ; before, during and after treatment

Locations

Country	Name	City	State
France	CHU de Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peptide receptor radionuclide therapy radio-induction variation of radiosensibility/reparation genes	Variations in gene transcripts will be registered and processed by a bio-informatician	Change from before at during treatment
Secondary	Evaluation of gene transcript variations	Analysis of gene transcript variation by quantitative real-time polymerase chain reaction	during treatment and until 48 hours after treatment
Secondary	Evaluation of interindividual variability with NONMEN software	Analysis of Lu-177 DOTATATE plasma concentration during treatment and 48 hours after treatment	during treatment and until 48 hours after treatment
Secondary	Evaluation of therapeutic response according to RECIST criteria	Correlation between gene variations and the therapeutic response assessed on RECIST criteria	6 months post therapy