There are 2 clinical trials
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.
177Lu-PP-F11N for Receptor Targeted Therapy and Imaging (Theranostics) of Metastatic Medullary Thyroid Cancer - a Pilot and a Phase I Study.. 177Lu-PP-F11N for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer. --- F11N ---
177Lu-PP-F11N for Receptor Targeted Therapy and Imaging (Theranostics) of Metastatic Medullary Thyroid Cancer - a Pilot and a Phase I Study.. 177Lu-PP-F11N for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer. --- F11N --- --- F11N ---
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 is a gastrin analogon, binding to cholecystokinin-2 receptors. --- F11N ---
In the phase I study investigators will determinate the maximum tolerated dose of 177Lu-PP-F11N in patients with MTC. --- F11N ---
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. --- F11N ---
Evaluation of in vivo stability of 177Lu-PP-F11N.. Phase 0: Metabolites. --- F11N ---
Measurement of the metabolites of 177Lu-PP-F11N with and without Physiogel infusion.. Phase I: Side reactions. --- F11N ---
Evaluation of side reactions of 177Lu-PP-F11N.. Phase 1: Biochemical response. --- F11N ---
Evaluation of in vivo stability of 177Lu-PP-F11N.. Phase 1: Metabolites. --- F11N ---
Measurement of the metabolites of 177Lu-PP-F11N.. Inclusion Criteria: 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 - 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 Exclusion Criteria: 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). --- F11N ---
Description: 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).
Measure: Phase 0: Scintigraphic visualisation rate Time: up to 4 weeksDescription: Phase I study: Determination of the maximum tolerated dose (MTD)
Measure: Phase I: Maximum tolerated dose Time: Up to 9 monthsDescription: Evaluation of the kidney radiation dose and the tumour-to-kidney radiation dose ratios with and without kidney protection (Physiogel). Composite measure.
Measure: Phase 0: Tumour-to-kidney radiation doses Time: 8 and 16 weeksDescription: Calculation of tumour and organ radiation doses.
Measure: Phase 0: Radiation doses Time: 8 and 16 weeksDescription: Evaluation of in vivo stability of 177Lu-PP-F11N.
Measure: Phase 0: In vivo stability Time: 8 and 16 weeksDescription: Measurement of the metabolites of 177Lu-PP-F11N with and without Physiogel infusion.
Measure: Phase 0: Metabolites Time: 8 and 16 weeksDescription: Evaluation of side reactions of 177Lu-PP-F11N.
Measure: Phase I: Side reactions Time: 8, 16 and 24 weeksDescription: Evaluation of biochemical response (decrease of calcitonin and calculation of calcitonin doubling time).
Measure: Phase 1: Biochemical response Time: For the duration of 24 months.Description: Evaluation of morphological therapy response (RECIST criteria).
Measure: Phase I: Morphological response Time: 0, 3 and 12 monthsDescription: Determination of the tumour detection rate and correlation with surgery/histology, if possible.
Measure: Phase I: Tumour detection rate Time: 8, 16 and 24 weeksDescription: Calculation of organ radiation doses after therapy and correlation with the determined MTD (composite measure).
Measure: Phase I: Organ radiation doses Time: 8, 16 and 24 weeksDescription: Determination of overall survival of patients after therapy.
Measure: Phase 1: Overall survival Time: Up to 5 yearsDescription: Evaluation of in vivo stability of 177Lu-PP-F11N.
Measure: Phase 1: In vivo stability Time: 8, 16 und 24 weeksDescription: Measurement of the metabolites of 177Lu-PP-F11N.
Measure: Phase 1: Metabolites Time: 8, 16 and 24 weeksThe 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.
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 Diseases Thyroid Neoplasms Carcinoma, Neuroendocrine 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 ---
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: Chromogranine A blood values will be compared to the radiation doses of the stomach.
Measure: Chromogranine 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-F11N