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

University Hospital Basel

Status and phase: Completed; Early Phase 1

Conditions: Thyroid Cancer, Medullary

Treatments: Drug: 177Lu-PP-F11N; Drug: Sacuitril

Study type: Interventional

Funder types: Other

Identifiers

NCT03647657

2018-00972

Details and patient eligibility

About

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.

Full 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.

Enrollment: 8 patients

Sex: All

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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8 participants in 2 patient groups

Entresto second

Experimental group

Description:

First intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N without and second injection with additional medication of Sacuitril (100 mg Entresto)(crossover)

Treatment:

Drug: Sacuitril

Drug: 177Lu-PP-F11N

Entresto first

Experimental group

Description:

First intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N with and second injection without additional medication of Sacuitril (100 mg Entresto)(crossover)

Treatment:

Drug: Sacuitril

Drug: 177Lu-PP-F11N