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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03667092
Recruitment Status : Recruiting
First Posted : September 12, 2018
Last Update Posted : August 2, 2019
Information provided by (Responsible Party):
University Hospital, Toulouse

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.

Condition or disease Intervention/treatment Phase
Midgut Neuroendocrine Tumors Biological: non-drug intervention type Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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
Actual Study Start Date : September 1, 2018
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

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 Name: Blood samples

Primary Outcome Measures :
  1. 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

Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03667092

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Contact: Isabelle BERRY, MD, PhD 0531156157 ext 33
Contact: Lavinia VIJA, MD, PhD 0531155647 ext 33

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CHU de Toulouse Recruiting
Toulouse, France, 31059
Sponsors and Collaborators
University Hospital, Toulouse
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Study Chair: Lavinia VIJA, MD, PhD University Hospital, Toulouse

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Responsible Party: University Hospital, Toulouse Identifier: NCT03667092    
Other Study ID Numbers: RC31/17/0356
First Posted: September 12, 2018    Key Record Dates
Last Update Posted: August 2, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Toulouse:
Lu-177 Dotatate
transcript analysis and variation
molecular biomarkers
midgut neuroendocrine tumors
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue