177Lu-PP-F11N for Receptor Targeted Therapy and Imaging (Theranostics) of Metastatic Medullary Thyroid Cancer - a Pilot and a Phase I Study.
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Phase 0: Scintigraphic visualisation rate
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.
In the pilot (phase 0) study investigators will correlate the tumour detection rate with the surgery and histology (proof of concept study). Furthermore, kidney protection and dosimetry studies will be performed in order to determine the kidney protection protocol and starting activity for the dose escalation study in the following, dose escalation (phase I) study. In the phase I study investigators will determinate the maximum tolerated dose of 177Lu-PP-F11N in patients with MTC. Furthermore, correlation with tumour radiation dose and treatment response as well as organ radiation doses and maximal tolerated dose will be performed in order to allow prospective individual patient tailored therapy planning. In the phase I study, participation is additionally possible for patients with well differentiated GEP-NET (grade 1-3) with a Ki67 index of up to 55% or NET of the lung or thymus (grade 1 and 2).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 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
- •Phase 0 study
- •Advanced MTC with elevated levels of calcitonin (> 100 pg/ml) and/or calcitonin-doubling time < 24 months before or after total thyroidectomy or
- •Patients with well differentiated GEP-NET (grade 1-3) with a Ki67 index of up to 55% or NET of the lung or thymus (grade 1 and 2) with low or missing expression of SST2-receptor and progressive disease within the last 6 months according to RECIST 1.1
- •Age > 18 years
- •Informed consent
- •Phase I study
- •Diagnostic, contrast medium enhanced CT scan neck/thorax/abdomen, not older than 4 weeks
- •Advanced MTC with elevated levels of calcitonin (> 100 pg/ml) and/or calcitonin-doubling time < 24 months before or after total thyroidectomy- Age > 18 Years
- •Informed consent
- •Curative surgical therapy not possible
排除标准
- •Phase 0 study
- •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
- •Knows allergic reaction on Physiogel or other gelatine products
- •Known, serious side reaction in the case of a former application of pentagastrin
- •Active, second malignancy oder remission after second malignancy < 5 years
- •Phase I study
- •Medication with Vandetanib 3 weeks before the study and during the study
- •Renal failure (calculated GFR < 50 ml/min per 1.73 m2 body surface).
- •Bone marrow failure (thrombocytes < 100 000/μl, leucocytes < 3 000/μl, hemoglobin < 10 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
研究组 & 干预措施
Phase 0: One arm; Phase I: One arm
Phase 0: 6 patients, intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N with and without Physiogel (crossover)
Phase I: expected 12 - 18 patients, intravenous application of max. 6 x 7-8 GBq 177Lu-PP-F11N (increasing number of applications by one in groups of three patients). All patients with or without Physiogel, depending on the results of the phase 0 study.
干预措施: 177Lu-PP-F11N (Drug)
结局指标
主要结局
Phase 0: Scintigraphic visualisation rate
时间窗: up to 4 weeks
Phase 0 study: Evaluation of the scintigraphic visualisation of metastases after test injection, verification of 177Lu-PP-F11N uptake in metastases and correlation with surgery/histology if possible (poof of principle study).
Phase I: Maximum tolerated dose
时间窗: Up to 9 months
Phase I study: Determination of the maximum tolerated dose (MTD)
次要结局
- Phase 0: Tumour-to-kidney radiation doses(8 and 16 weeks)
- Phase 1: Metabolites(8, 16 and 24 weeks)
- Phase 0: Metabolites(8 and 16 weeks)
- Phase 1: Biochemical response(For the duration of 24 months.)
- Phase I: Organ radiation doses(8, 16 and 24 weeks)
- Phase 0: In vivo stability(8 and 16 weeks)
- Phase I: Side reactions(8, 16 and 24 weeks)
- Phase I: Morphological response(0, 3 and 12 months)
- Phase I: Tumour detection rate(8, 16 and 24 weeks)
- Phase 0: Radiation doses(8 and 16 weeks)
- Phase 1: Overall survival(Up to 5 years)
- Phase 1: In vivo stability(8, 16 und 24 weeks)