Neuroendocrine Tumor GEP Grade 1-3, Neuroendocrine Tumor of the Lung Grade 1 and 2, Neuroendocrine Tumor of the Thymus Grade 1 and 2, Thyroid Cancer, Medullary
Conditions
Keywords
Calcitonin, Medullary thyroid carcinoma, Peptide receptor radionuclide therapy, Gastrin, Cholecystokinin-2 receptor, Neuroendocrine tumor
Brief summary
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).
Interventions
DRUG177Lu-PP-F11N
Sponsors
University Hospital, Basel, Switzerland
Krebsforschung Schweiz, Bern, Switzerland
Center for Proton Therapy, Paul Scherrer Institute, Villigen,Switzerland
University Hospital, Zürich
University Hospital Freiburg
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 0: Scintigraphic visualisation rate | 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 | Up to 9 months | Phase I study: Determination of the maximum tolerated dose (MTD) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 0: Tumour-to-kidney radiation doses | 8 and 16 weeks | Evaluation of the kidney radiation dose and the tumour-to-kidney radiation dose ratios with and without kidney protection (Physiogel). Composite measure. |
| Phase 0: Radiation doses | 8 and 16 weeks | Calculation of tumour and organ radiation doses. |
| Phase 0: In vivo stability | 8 and 16 weeks | Evaluation of in vivo stability of 177Lu-PP-F11N. |
| Phase 0: Metabolites | 8 and 16 weeks | Measurement of the metabolites of 177Lu-PP-F11N with and without Physiogel infusion. |
| Phase I: Side reactions | 8, 16 and 24 weeks | Evaluation of side reactions of 177Lu-PP-F11N. |
| Phase 1: Biochemical response | For the duration of 24 months. | Evaluation of biochemical response (decrease of calcitonin and calculation of calcitonin doubling time). |
| Phase I: Morphological response | 0, 3 and 12 months | Evaluation of morphological therapy response (RECIST criteria). |
| Phase I: Tumour detection rate | 8, 16 and 24 weeks | Determination of the tumour detection rate and correlation with surgery/histology, if possible. |
| Phase I: Organ radiation doses | 8, 16 and 24 weeks | Calculation of organ radiation doses after therapy and correlation with the determined MTD (composite measure). |
| Phase 1: Overall survival | Up to 5 years | Determination of overall survival of patients after therapy. |
| Phase 1: In vivo stability | 8, 16 und 24 weeks | Evaluation of in vivo stability of 177Lu-PP-F11N. |
| Phase 1: Metabolites | 8, 16 and 24 weeks | Measurement of the metabolites of 177Lu-PP-F11N. |
Countries
Switzerland
Contacts
PRINCIPAL_INVESTIGATORChristof Rottenburger, Dr. med.
University Hospital, Basel, Switzerland
STUDY_DIRECTORDamian Wild, Prof Dr Dr
University Hospital, Basel, Switzerland
Outcome results
None listed