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

NCT ID: NCT03647657

Last Updated: 2022-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-13
• Study Completion Date: 2021-12-14

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.

Conditions

Thyroid Cancer, Medullary

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Entresto second

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)

Group Type: EXPERIMENTAL

177Lu-PP-F11N

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Entresto first

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)

Group Type: EXPERIMENTAL

177Lu-PP-F11N

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Sacuitril

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

Intervention Type: DRUG

Other Intervention Names

Radiopharmakon; Entresto

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Krebsforschung Schweiz, Bern, Switzerland

OTHER

Sponsor Role: collaborator

Center for Proton Therapy, Paul Scherrer Institute, Villigen,Switzerland

OTHER

Sponsor Role: collaborator

University Hospital, Zürich

OTHER

Sponsor Role: collaborator

University Hospital Freiburg

OTHER

Sponsor Role: collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christof Rottenburger, Dr. med.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Basel, Clinic for radiology and nuclear medicine

Damian Wild, PhD Dr

Role: STUDY_DIRECTOR

University Hospital Basel, Clinic for radiology and nuclear medicine

Locations

University Hospital Basel, Clinic for radiology and nuclear medicine

Basel, , Switzerland

Countries

Switzerland

References

Sauter AW, Mansi R, Hassiepen U, Muller L, Panigada T, Wiehr S, Wild AM, Geistlich S, Behe M, Rottenburger C, Wild D, Fani M. Targeting of the Cholecystokinin-2 Receptor with the Minigastrin Analog 177Lu-DOTA-PP-F11N: Does the Use of Protease Inhibitors Further Improve In Vivo Distribution? J Nucl Med. 2019 Mar;60(3):393-399. doi: 10.2967/jnumed.118.207845. Epub 2018 Jul 12.

Reference Type: RESULT

PMID: 30002107 (View on PubMed)

Rottenburger C, Hentschel M, Furstner M, McDougall L, Kottoros D, Kaul F, Mansi R, Fani M, Vija AH, Schibli R, Geistlich S, Behe M, Christ ER, Wild D. In-vivo inhibition of neutral endopeptidase 1 results in higher absorbed tumor doses of [177Lu]Lu-PP-F11N in humans: the lumed phase 0b study. EJNMMI Res. 2024 Apr 6;14(1):37. doi: 10.1186/s13550-024-01101-w.

Reference Type: DERIVED

PMID: 38581480 (View on PubMed)

Related Links

https://www.unispital-basel.ch/en

University Hospital Basel Homepage

Other Identifiers

2018-00972

Identifier Type: -

Identifier Source: org_study_id