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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 64 Years
Gender	All

More Inclusion & Exclusion 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT03647657
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Early Phase 1
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	University Hospital, Basel, Switzerland
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Christof Rottenburger, Dr. med.Damian Wild, PhD Dr
Principal Investigator Affiliation	University Hospital Basel, Clinic for radiology and nuclear medicineUniversity Hospital Basel, Clinic for radiology and nuclear medicine
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Switzerland
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Thyroid Cancer, Medullary
Study Website:	View Trial Website

Additional Details

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.

Arms & Interventions

Arms

Experimental: 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)

Experimental: 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)

Interventions

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

Drug: - Sacuitril

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

Contact a Trial Team

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International Sites

Basel, Switzerland

Status

Recruiting

Address

University Hospital Basel, Clinic for radiology and nuclear medicine

Basel, , 4031

Site Contact

Christof Rottenburger, Dr. med.

christof.rottenburger@ubs.ch

0041613286551

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