177Lu-PP-F11N for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer.

Study Overview
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Brief Summary
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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).

Official Title
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177Lu-PP-F11N for Receptor Targeted Therapy and Imaging (Theranostics) of Metastatic Medullary Thyroid Cancer - a Pilot and a Phase I Study.

Conditions
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Neuroendocrine Tumor GEP Grade 1-3, Thyroid Cancer, Medullary, Neuroendocrine Tumor of the Lung Grade 1 and 2, Neuroendocrine Tumor of the Thymus Grade 1 and 2

Intervention / Treatment
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* Drug: 177Lu-PP-F11N


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 0: One arm; Phase I: One arm<br>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. | Drug: 177Lu-PP-F11N<br> <br> * Other names: Cholecystokinin-2 receptor ligand;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 0: Scintigraphic visualisation rate | 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). | up to 4 weeks | 
| Phase I: Maximum tolerated dose | Phase I study: Determination of the maximum tolerated dose (MTD) | Up to 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 0: Tumour-to-kidney radiation doses | Evaluation of the kidney radiation dose and the tumour-to-kidney radiation dose ratios with and without kidney protection (Physiogel). Composite measure. | 8 and 16 weeks | 
| Phase 0: Radiation doses | Calculation of tumour and organ radiation doses. | 8 and 16 weeks | 
| Phase 0: In vivo stability | Evaluation of in vivo stability of 177Lu-PP-F11N. | 8 and 16 weeks | 
| Phase 0: Metabolites | Measurement of the metabolites of 177Lu-PP-F11N with and without Physiogel infusion. | 8 and 16 weeks | 
| Phase I: Side reactions | Evaluation of side reactions of 177Lu-PP-F11N. | 8, 16 and 24 weeks | 
| Phase 1: Biochemical response | Evaluation of biochemical response (decrease of calcitonin and calculation of calcitonin doubling time). | For the duration of 24 months. | 
| Phase I: Morphological response | Evaluation of morphological therapy response (RECIST criteria). | 0, 3 and 12 months | 
| Phase I: Tumour detection rate | Determination of the tumour detection rate and correlation with surgery/histology, if possible. | 8, 16 and 24 weeks | 
| Phase I: Organ radiation doses | Calculation of organ radiation doses after therapy and correlation with the determined MTD (composite measure). | 8, 16 and 24 weeks | 
| Phase 1: Overall survival | Determination of overall survival of patients after therapy. | Up to 5 years | 
| Phase 1: In vivo stability | Evaluation of in vivo stability of 177Lu-PP-F11N. | 8, 16 und 24 weeks | 
| Phase 1: Metabolites | Measurement of the metabolites of 177Lu-PP-F11N. | 8, 16 and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Calcitonin, Medullary thyroid carcinoma, Peptide receptor radionuclide therapy, Gastrin, Cholecystokinin-2 receptor, Neuroendocrine tumor