177Lu-PP-F11N for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer.

Thyroid Cancer, Medullary Clinical Trial

— Lumed  

Official title:

177Lu-PP-F11N for Receptor Targeted Therapy and Imaging (Theranostics) of Metastatic Medullary Thyroid Cancer - a Pilot and a Phase I Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02088645
• Other study ID #: KFS-3170-02-2013
• Status: Recruiting
• Phase: Phase 1
• Start date: April 2015
• Est. completion date: June 2025

Study information

• Verified date: November 2023
• Source: University Hospital, Basel, Switzerland
• Contact: Christof Rottenburger, Dr. med.
• Phone: 0041613286551
• Email: Christof.Rottenburger[@]usb.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: June 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Neoplasms
• Neoplasms
• Neuroendocrine Tumor GEP Grade 1-3
• Neuroendocrine Tumor of the Lung Grade 1 and 2
• Neuroendocrine Tumor of the Thymus Grade 1 and 2
• Neuroendocrine Tumors
• Thyroid Cancer, Medullary
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Drug:
• 177Lu-PP-F11N

Locations

Country	Name	City	State
Switzerland	University Hospital Basel, Clinic for radiology and nuclear medicine	Basel

Sponsors (5)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	Center for Proton Therapy, Paul Scherrer Institute, Villigen,Switzerland, Krebsforschung Schweiz, Bern, Switzerland, University Hospital Freiburg, University Hospital, Zürich

Country where clinical trial is conducted

Switzerland, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 0: Scintigraphic visualisation rate	Phase 0 study: Evaluation of the scintigraphic visualisation of metastases after test injection, verification of 177Lu-PP-F11N uptake in metastases and correlation with surgery/histology if possible (poof of principle study).	up to 4 weeks
Primary	Phase I: Maximum tolerated dose	Phase I study: Determination of the maximum tolerated dose (MTD)	Up to 9 months
Secondary	Phase 0: Tumour-to-kidney radiation doses	Evaluation of the kidney radiation dose and the tumour-to-kidney radiation dose ratios with and without kidney protection (Physiogel). Composite measure.	8 and 16 weeks
Secondary	Phase 0: Radiation doses	Calculation of tumour and organ radiation doses.	8 and 16 weeks
Secondary	Phase 0: In vivo stability	Evaluation of in vivo stability of 177Lu-PP-F11N.	8 and 16 weeks
Secondary	Phase 0: Metabolites	Measurement of the metabolites of 177Lu-PP-F11N with and without Physiogel infusion.	8 and 16 weeks
Secondary	Phase I: Side reactions	Evaluation of side reactions of 177Lu-PP-F11N.	8, 16 and 24 weeks
Secondary	Phase 1: Biochemical response	Evaluation of biochemical response (decrease of calcitonin and calculation of calcitonin doubling time).	For the duration of 24 months.
Secondary	Phase I: Morphological response	Evaluation of morphological therapy response (RECIST criteria).	0, 3 and 12 months
Secondary	Phase I: Tumour detection rate	Determination of the tumour detection rate and correlation with surgery/histology, if possible.	8, 16 and 24 weeks
Secondary	Phase I: Organ radiation doses	Calculation of organ radiation doses after therapy and correlation with the determined MTD (composite measure).	8, 16 and 24 weeks
Secondary	Phase 1: Overall survival	Determination of overall survival of patients after therapy.	Up to 5 years
Secondary	Phase 1: In vivo stability	Evaluation of in vivo stability of 177Lu-PP-F11N.	8, 16 und 24 weeks
Secondary	Phase 1: Metabolites	Measurement of the metabolites of 177Lu-PP-F11N.	8, 16 and 24 weeks

External Links

•   Homepage University Hospital Basel