Thyroid Cancer, Medullary
Conditions
Keywords
Calcitonin, Medullary thyroid carcinoma, Peptide receptor radionuclide therapy, Gastrin, Cholecystokinin-2 receptor
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.
Detailed description
A phase 0 study (Lumed study part A) was already performed, showing low toxicity of 177Lu-PP-F11N and tumor uptake in all patients. Co-injection of Physiogel (Gelofusin) showed insignificant reduction of kidney uptake and can therefore be omitted for a radionuclide therapy with 177Lu-PP-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. 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. The inclusion of 8 patients is planned.
Interventions
DRUG177Lu-PP-F11N
Intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N with and without co-medication with Sacuitril (100 mg Entresto) in each patient
DRUGSacuitril
Medication with Sacuitril (100 mg Entresto) additional to the injection of 177Lu-PP-F11N
Sponsors
Krebsforschung Schweiz, Bern, Switzerland
Center for Proton Therapy, Paul Scherrer Institute, Villigen,Switzerland
University Hospital, Zürich
University Hospital Freiburg
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
No masking
Intervention model description
Group 1 patients will receive first 177Lu-PP-F11N alone, second 177Lu-PP-F11N in combination with Sacuitril. Group 2 patients will first receive 177Lu-PP-F11N in combination with Sacuitril, second 177Lu-PP-F11N alone. Affiliation of patients to Groups 1 and 2 will be randomised.
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Advanced MTC with elevated levels of calcitonin (\> 100 pg/ml) and/or calcitonin-doubling time \< 24 months before or after total thyroidectomy * 68Ga-DOTATOC PET/CT not older than 12 weeks * Age \> 18 years * Informed consent
Exclusion criteria
* 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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor radiation doses | Measurement up to 72 hours after each injection of 177Lu-PP-F11N | Evaluation of the radiation doses in tumor tissue from MTC after injection of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kidney radiation doses | Measurement up to 72 hours after each injection of 177Lu-PP-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) |
| Organ radiation doses | Measurement up to 72 hours after each injection of 177Lu-PP-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) |
| In-vivo stability | Blood samples for measurement 5 and 30 minutes post injection of 177Lu-PP-F11N | Measurement (HPLC) of the in-vivo stability of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto). |
| Autoradiography | Through study completion, up to 18 months | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Chromogranin A | Measurement up to 72 hours after the first injection of 177Lu-PP-F11N | Chromogranin A blood values will be compared to the radiation doses of the stomach. |
| 68Ga-DOTATOC PET/CT | Measurement up to 72 hours after each injection of 177Lu-PP-F11N | Comparison of tumor imaging by 68Ga-DOTATOC PET/CT and 177Lu-PP-F11N SPECT/CT |
Countries
Switzerland
Outcome results
None listed