177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer

Early Phase 1CompletedNCT03647657

University Hospital, Basel, Switzerland8 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Thyroid Cancer, Medullary

Interventions

177Lu-PP-F11NDRUG

Intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N with and without co-medication with Sacuitril (100 mg Entresto) in each patient

SacuitrilDRUG

Medication with Sacuitril (100 mg Entresto) additional to the injection of 177Lu-PP-F11N

Eligibility

Sex: ALLMin age: 18 YearsMax age: 64 Years

Medical Language ↔ Plain English

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

Locations (1)

University Hospital Basel, Clinic for radiology and nuclear medicine

Basel, Switzerland

Outcomes

Primary Outcomes

Tumor radiation doses

Evaluation of the radiation doses in tumor tissue from MTC after injection of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto)

Time frame: Measurement up to 72 hours after each injection of 177Lu-PP-F11N

Secondary Outcomes

Kidney radiation doses

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)

Time frame: Measurement up to 72 hours after each injection of 177Lu-PP-F11N

Organ radiation doses

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)

Time frame: Measurement up to 72 hours after each injection of 177Lu-PP-F11N

In-vivo stability

Measurement (HPLC) of the in-vivo stability of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto).

Time frame: Blood samples for measurement 5 and 30 minutes post injection of 177Lu-PP-F11N

Autoradiography

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.

Time frame: Through study completion, up to 18 months

Data from ClinicalTrials.gov

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