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

Thyroid Cancer, Medullary Clinical Trial

Official title:

177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer (Lumed Phase 0/B)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03647657
• Other study ID #: 2018-00972
• Status: Completed
• Phase: Early Phase 1
• Start date: December 13, 2018
• Est. completion date: December 14, 2021

Study information

• Verified date: February 2022
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: December 14, 2021
• Est. primary completion date: December 14, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Thyroid Cancer, Medullary
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

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

Locations

Country	Name	City	State
Switzerland	University Hospital Basel, Clinic for radiology and nuclear medicine	Basel

Sponsors (5)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	Center for Proton Therapy, Paul Scherrer Institute, Villigen,Switzerland, Krebsforschung Schweiz, Bern, Switzerland, University Hospital Freiburg, University Hospital, Zürich

Country where clinical trial is conducted

Switzerland, 

References & Publications (1)

Sauter AW, Mansi R, Hassiepen U, Muller L, Panigada T, Wiehr S, Wild AM, Geistlich S, Béhé M, Rottenburger C, Wild D, Fani M. Targeting of the Cholecystokinin-2 Receptor with the Minigastrin Analog (177)Lu-DOTA-PP-F11N: Does the Use of Protease Inhibitors — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Chromogranin A	Chromogranin A blood values will be compared to the radiation doses of the stomach.	Measurement up to 72 hours after the first injection of 177Lu-PP-F11N
Other	68Ga-DOTATOC PET/CT	Comparison of tumor imaging by 68Ga-DOTATOC PET/CT and 177Lu-PP-F11N SPECT/CT	Measurement up to 72 hours after each injection of 177Lu-PP-F11N
Primary	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)	Measurement up to 72 hours after each injection of 177Lu-PP-F11N
Secondary	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)	Measurement up to 72 hours after each injection of 177Lu-PP-F11N
Secondary	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)	Measurement up to 72 hours after each injection of 177Lu-PP-F11N
Secondary	In-vivo stability	Measurement (HPLC) of the in-vivo stability of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto).	Blood samples for measurement 5 and 30 minutes post injection of 177Lu-PP-F11N
Secondary	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.	Through study completion, up to 18 months

External Links

•   University Hospital Basel Homepage