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.
Name: 177Lu-PP-F11N
Name: Sacuitril
Description: Evaluation of the radiation doses in tumor tissue from MTC after injection of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto)
Measure: Tumor radiation doses Time: Measurement up to 72 hours after each injection of 177Lu-PP-F11NDescription: Evaluation of the radiation doses in the kidneys and the tumor-to-kidney dose ratios after injection of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto)
Measure: Kidney radiation doses Time: Measurement up to 72 hours after each injection of 177Lu-PP-F11NDescription: Evaluation of the radiation doses in other organs and the appropriate organ-to-kidney dose ratios after injection of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto)
Measure: Organ radiation doses Time: Measurement up to 72 hours after each injection of 177Lu-PP-F11NDescription: Measurement (HPLC) of the in-vivo stability of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto).
Measure: In-vivo stability Time: Blood samples for measurement 5 and 30 minutes post injection of 177Lu-PP-F11NDescription: In case of surgery with available tumor tissue samples, imaging results will be compared with autoradiographic analysis of somatostatine- and CCK2-receptor expression in tumor tissue.
Measure: Autoradiography Time: Through study completion, up to 18 monthsDescription: Chromogranin A blood values will be compared to the radiation doses of the stomach.
Measure: Chromogranin A Time: Measurement up to 72 hours after the first injection of 177Lu-PP-F11NDescription: Comparison of tumor imaging by 68Ga-DOTATOC PET/CT and 177Lu-PP-F11N SPECT/CT
Measure: 68Ga-DOTATOC PET/CT Time: Measurement up to 72 hours after each injection of 177Lu-PP-F11NAllocation: Randomized
Crossover Assignment
There is one SNP
177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer (Lumed Phase 0/B). --- F11N ---
177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer 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). --- F11N ---
177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer 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). --- F11N --- --- F11N ---
177Lu-PP-F11N is a gastrin analogon, binding to cholecystokinin-2 receptors. --- F11N ---
Evaluation of the radiation doses in tumor tissue from MTC after injection of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto). --- F11N ---
Evaluation of the radiation doses in the kidneys and the tumor-to-kidney dose ratios after injection of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto). --- F11N ---
Evaluation of the radiation doses in other organs and the appropriate organ-to-kidney dose ratios after injection of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto). --- F11N ---
Measurement (HPLC) of the in-vivo stability of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto).. Autoradiography. --- F11N ---
Comparison of tumor imaging by 68Ga-DOTATOC PET/CT and 177Lu-PP-F11N SPECT/CT. --- F11N ---
- 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 Thyroid Cancer, Medullary Thyroid Neoplasms Thyroid Diseases A phase 0 study (Lumed study part A) was already performed, showing low toxicity of 177Lu-PP-F11N and tumor uptake in all patients. --- F11N ---
Co-injection of Physiogel (Gelofusin) showed insignificant reduction of kidney uptake and can therefore be omitted for a radionuclide therapy with 177Lu-PP-F11N. --- 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. --- F11N ---
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. --- F11N ---