Title
177Lu-PP-F11N for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer.
177Lu-PP-F11N for Receptor Targeted Therapy and Imaging (Theranostics) of Metastatic Medullary Thyroid Cancer - a Pilot and a Phase I Study.
Phase
Phase 1Lead Sponsor
University of BernStudy Type
InterventionalStatus
RecruitingIntervention/Treatment
177lu-pp-f11n ...Study Participants
24The 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).
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.
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 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 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). 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
