Clinical trial NCT03647657: 177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer
Official title: 177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer (Lumed Phase 0/B)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Thyroid Cancer, Medullary
Keywords: Calcitonin
Medullary thyroid carcinoma
Peptide receptor radionuclide therapy
Gastrin
Cholecystokinin-2 receptor
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Krebsforschung Schweiz, Bern, Switzerland
name: Center for Proton Therapy, Paul Scherrer Institute, Villigen,Switzerland
name: University Hospital, Zürich
name: University Hospital Freiburg
First posted: 2018-08-27
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Tumor radiation doses
timeFrame: Measurement up to 72 hours after each injection of 177Lu-PP-F11N
Secondary outcomes:
measure: Kidney radiation doses
timeFrame: Measurement up to 72 hours after each injection of 177Lu-PP-F11N
measure: Organ radiation doses
timeFrame: Measurement up to 72 hours after each injection of 177Lu-PP-F11N
measure: In-vivo stability
timeFrame: Blood samples for measurement 5 and 30 minutes post injection of 177Lu-PP-F11N
measure: Autoradiography
timeFrame: Through study completion, up to 18 months
Other outcomes:
measure: Chromogranin A
timeFrame: Measurement up to 72 hours after the first injection of 177Lu-PP-F11N
measure: 68Ga-DOTATOC PET/CT
timeFrame: Measurement up to 72 hours after each injection of 177Lu-PP-F11N
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Clinic for radiology and nuclear medicine
Study officials:
affiliation: University Hospital Basel, Clinic for radiology and nuclear medicine
name: Christof Rottenburger, Dr. med.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Basel, Clinic for radiology and nuclear medicine
name: Damian Wild, PhD Dr
role: STUDY_DIRECTOR
References:
citation: 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.