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

NCT03647657 | Completed Early Phase 1 DMC

• 1 other identifier: 2018-00972
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Thyroid Cancer, Medullary

Keywords

Calcitonin; Medullary thyroid carcinoma; Peptide receptor radionuclide therapy; Gastrin; Cholecystokinin-2 receptor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Kidney radiation doses

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

• Organ radiation doses

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

• In-vivo stability

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

• Autoradiography

  Through study completion, up to 18 months

Other Outcomes (2)

• Chromogranin A

  Measurement up to 72 hours after the first injection of 177Lu-PP-F11N

• 68Ga-DOTATOC PET/CT

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

Study Arms (2)

Entresto second

EXPERIMENTAL

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)

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

Entresto first

EXPERIMENTAL

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)

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

Interventions

177Lu-PP-F11N 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

Also known as: Radiopharmakon

Entresto first; Entresto second

Sacuitril DRUG

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

Also known as: Entresto

Entresto first; Entresto second

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Advanced MTC with elevated levels of calcitonin (\> 100 pg/ml) and/or calcitonin-doubling time \< 24 months before or after total thyroidectomy
• Ga-DOTATOC PET/CT not older than 12 weeks
• Age \> 18 years
• Informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Krebsforschung Schweiz, Bern, Switzerland: collaborator
• Center for Proton Therapy, Paul Scherrer Institute, Villigen,Switzerland: collaborator
• University Hospital, Zürich: collaborator
• University Hospital Freiburg: collaborator

Study Sites (1)

University Hospital Basel, Clinic for radiology and nuclear medicine

Basel, 4031, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 30002107 RESULT

• 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.

  PMID: 38581480 DERIVED

Related Links

• University Hospital Basel Homepage

MeSH Terms

Conditions

Thyroid cancer, medullary; Carcinoma, Medullary

Interventions

sacubitril and valsartan sodium hydrate drug combination

Condition Hierarchy (Ancestors)

Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Nerve Tissue

Study Officials

• Christof Rottenburger, Dr. med.

  University Hospital Basel, Clinic for radiology and nuclear medicine

  PRINCIPAL INVESTIGATOR

• Damian Wild, PhD Dr

  University Hospital Basel, Clinic for radiology and nuclear medicine

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: No masking
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Group 1 patients will receive first 177Lu-PP-F11N alone, second 177Lu-PP-F11N in combination with Sacuitril. Group 2 patients will first receive 177Lu-PP-F11N in combination with Sacuitril, second 177Lu-PP-F11N alone. Affiliation of patients to Groups 1 and 2 will be randomised.

Study Record Dates

• First Submitted: August 20, 2018
• First Posted: August 27, 2018
• Study Start: December 13, 2018
• Primary Completion: December 14, 2021
• Study Completion: December 14, 2021
• Last Updated: February 10, 2022

Record last verified: 2022-02

Locations

CH (1)