177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer (Lumed Phase 0/B)
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Tumor radiation doses
研究概览
简要总结
The purpose of this study is to determine the use of 177Lu-PP-F11N for imaging and therapy of patients with advanced medullary thyroid carcinoma (MTC). 177Lu-PP-F11N is a gastrin analogon, binding to cholecystokinin-2 receptors. This receptors show an overexpression on more than 90 % of medullary thyroid carcinomas.
详细描述
A phase 0 study (Lumed study part A) was already performed, showing low toxicity of 177Lu-PP-F11N and tumor uptake in all patients. Co-injection of Physiogel (Gelofusin) showed insignificant reduction of kidney uptake and can therefore be omitted for a radionuclide therapy with 177Lu-PP-F11N. In this study, the effect of the NEP-1 inhibitor Sacuitril on the in-vivo stability of 177Lu-PP-F11N and the uptake, respectively radiation doses in MTC metastases and organs will be evaluated, using a cross-over design already used for the Lumed part A study. Each patient will receive two injections of 177Lu-PP-F11N, with and without additional medication with Sacuitril Imaging findings, acquired by SPECT/CT, will be compared to imaging with 68Ga-DOTATOC positron emission tomography (PET)/CT. The inclusion of 8 patients is planned.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
盲法说明
No masking
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Advanced MTC with elevated levels of calcitonin (> 100 pg/ml) and/or calcitonin-doubling time < 24 months before or after total thyroidectomy
- •68Ga-DOTATOC PET/CT not older than 12 weeks
- •Age > 18 years
- •Informed consent
排除标准
- •Medication with Vandetanib 3 weeks before the study and during the study
- •Renal failure (calculated glomerular filtration rate (GFR) < 60 ml/min per 1.73 m2 body surface).
- •Bone marrow failure (thrombocytes < 70 000/μl, leucocytes < 2 500/μl, hemoglobin < 8 g/dl).
- •Pregnancy and breast feeding
- •Known, serious side reaction in the case of a former application of pentagastrin
- •Active, second malignancy oder remission after second malignancy < 5 years
- •Age over 64 years
- •Systolic bood pressure < 112 mmHg at the time of screening
- •Simultaneous medication with angiotensin converting enzyme (ACE)-inhibitors, or withdrawal for less than 36 h prior to the medication with Entresto or simultaneous medication with AT-II-receptor blockers
- •Known intolerance to Sacubitril or Valsartan
- •Known angioedema in anamnesis in the context of a medication with an ACE-inhibitor or an AT-II-receptor blocker
研究组 & 干预措施
Entresto second
First intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N without and second injection with additional medication of Sacuitril (100 mg Entresto)(crossover)
干预措施: 177Lu-PP-F11N (Drug)
Entresto second
First intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N without and second injection with additional medication of Sacuitril (100 mg Entresto)(crossover)
干预措施: Sacuitril (Drug)
Entresto first
First intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N with and second injection without additional medication of Sacuitril (100 mg Entresto)(crossover)
干预措施: 177Lu-PP-F11N (Drug)
Entresto first
First intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N with and second injection without additional medication of Sacuitril (100 mg Entresto)(crossover)
干预措施: Sacuitril (Drug)
结局指标
主要结局
Tumor radiation doses
时间窗: Measurement up to 72 hours after each injection of 177Lu-PP-F11N
Evaluation of the radiation doses in tumor tissue from MTC after injection of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto)
次要结局
- Organ radiation doses(Measurement up to 72 hours after each injection of 177Lu-PP-F11N)
- In-vivo stability(Blood samples for measurement 5 and 30 minutes post injection of 177Lu-PP-F11N)
- Kidney radiation doses(Measurement up to 72 hours after each injection of 177Lu-PP-F11N)
- Autoradiography(Through study completion, up to 18 months)