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

Early Phase 1

Completed

• Conditions: Thyroid Cancer, Medullary
• Interventions: Drug: 177Lu-PP-F11N; Drug: Sacuitril

• Registration Number: NCT03647657
• Lead Sponsor: University Hospital, Basel, Switzerland

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.

Study Timeline

• Study First Submitted: 2018-08-20
• Study First Submitted QC: 2018-08-22
• Study First Posted: 2018-08-27
• Study Start: 2018-12-13
• Primary Completion: 2021-12-14
• Study Completion: 2021-12-14
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-09
• Last Update Posted: 2022-02-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Entresto first	177Lu-PP-F11N	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)
Entresto second	177Lu-PP-F11N	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)
Entresto first	Sacuitril	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)
Entresto second	Sacuitril	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)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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).
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)
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.

Trial Locations

Locations (1)

University Hospital Basel, Clinic for radiology and nuclear medicine; 🇨🇭 Basel, Switzerland