Clinical trial NCT02088645: 177Lu-PP-F11N for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer.
Official title: 177Lu-PP-F11N for Receptor Targeted Therapy and Imaging (Theranostics) of Metastatic Medullary Thyroid Cancer - a Pilot and a Phase I Study.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Thyroid Cancer, Medullary
Neuroendocrine Tumor of the Lung Grade 1 and 2
Neuroendocrine Tumor of the Thymus Grade 1 and 2
Neuroendocrine Tumor GEP Grade 1-3
Keywords: Calcitonin
Medullary thyroid carcinoma
Peptide receptor radionuclide therapy
Gastrin
Cholecystokinin-2 receptor
Neuroendocrine tumor
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: 2014-03-17
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

In the pilot (phase 0) study investigators will correlate the tumour detection rate with the surgery and histology (proof of concept study). Furthermore, kidney protection and dosimetry studies will be performed in order to determine the kidney protection protocol and starting activity for the dose escalation study in the following, dose escalation (phase I) study. In the phase I study investigators will determinate the maximum tolerated dose of 177Lu-PP-F11N in patients with MTC. Furthermore, correlation with tumour radiation dose and treatment response as well as organ radiation doses and maximal tolerated dose will be performed in order to allow prospective individual patient tailored therapy planning. In the phase I study, participation is additionally possible for patients with well differentiated GEP-NET (grade 1-3) with a Ki67 index of up to 55% or NET of the lung or thymus (grade 1 and 2).


Eligibility criteria: Inclusion Criteria:

Phase 0 study

* Advanced MTC with elevated levels of calcitonin (\> 100 pg/ml) and/or calcitonin-doubling time \< 24 months before or after total thyroidectomy or
* Patients with well differentiated GEP-NET (grade 1-3) with a Ki67 index of up to 55% or NET of the lung or thymus (grade 1 and 2) with low or missing expression of SST2-receptor and progressive disease within the last 6 months according to RECIST 1.1
* Age \> 18 years
* Informed consent

Phase I study

* Diagnostic, contrast medium enhanced CT scan neck/thorax/abdomen, not older than 4 weeks
* Advanced MTC with elevated levels of calcitonin (\> 100 pg/ml) and/or calcitonin-doubling time \< 24 months before or after total thyroidectomy- Age \> 18 Years
* Informed consent
* Curative surgical therapy not possible

Exclusion Criteria:

Phase 0 study

* 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
* Knows allergic reaction on Physiogel or other gelatine products
* Known, serious side reaction in the case of a former application of pentagastrin
* Active, second malignancy oder remission after second malignancy \< 5 years

Phase I study

* Medication with Vandetanib 3 weeks before the study and during the study
* Renal failure (calculated GFR \< 50 ml/min per 1.73 m2 body surface).
* Bone marrow failure (thrombocytes \< 100 000/μl, leucocytes \< 3 000/μl, hemoglobin \< 10 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

Primary outcomes:
measure: Phase 0: Scintigraphic visualisation rate
timeFrame: up to 4 weeks
measure: Phase I: Maximum tolerated dose
timeFrame: Up to 9 months
Secondary outcomes:
measure: Phase 0: Tumour-to-kidney radiation doses
timeFrame: 8 and 16 weeks
measure: Phase 0: Radiation doses
timeFrame: 8 and 16 weeks
measure: Phase 0: In vivo stability
timeFrame: 8 and 16 weeks
measure: Phase 0: Metabolites
timeFrame: 8 and 16 weeks
measure: Phase I: Side reactions
timeFrame: 8, 16 and 24 weeks
measure: Phase 1: Biochemical response
timeFrame: For the duration of 24 months.
measure: Phase I: Morphological response
timeFrame: 0, 3 and 12 months
measure: Phase I: Tumour detection rate
timeFrame: 8, 16 and 24 weeks
measure: Phase I: Organ radiation doses
timeFrame: 8, 16 and 24 weeks
measure: Phase 1: Overall survival
timeFrame: Up to 5 years
measure: Phase 1: In vivo stability
timeFrame: 8, 16 und 24 weeks
measure: Phase 1: Metabolites
timeFrame: 8, 16 and 24 weeks
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Clinic for radiology and nuclear medicine
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Christof Rottenburger, Dr. med.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Basel, Switzerland
name: Damian Wild, Prof Dr 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.
citation: Rottenburger C, Nicolas GP, McDougall L, Kaul F, Cachovan M, Vija AH, Schibli R, Geistlich S, Schumann A, Rau T, Glatz K, Behe M, Christ ER, Wild D. Cholecystokinin 2 Receptor Agonist 177Lu-PP-F11N for Radionuclide Therapy of Medullary Thyroid Carcinoma: Results of the Lumed Phase 0a Study. J Nucl Med. 2020 Apr;61(4):520-526. doi: 10.2967/jnumed.119.233031. Epub 2019 Sep 13.