Pilot Study for Measuring Molecular Biomarkers and Their Capacity to Characterize Radionuclide Therapy With Lu-177 DOTATATE) in Metastatic G1-G2 Neuroendocrine Midgut Tumors
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Peptide receptor radionuclide therapy radio-induction variation of radiosensibility/reparation genes
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
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.
干预措施: non-drug intervention type (Biological)
结局指标
主要结局
Peptide receptor radionuclide therapy radio-induction variation of radiosensibility/reparation genes
时间窗: Change from before at during treatment
Variations in gene transcripts will be registered and processed by a bio-informatician
次要结局
- Evaluation of therapeutic response according to RECIST criteria(6 months post therapy)
- Evaluation of gene transcript variations(during treatment and until 48 hours after treatment)
- Evaluation of interindividual variability with NONMEN software(during treatment and until 48 hours after treatment)