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

NCT02088645 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: KFS-3170-02-2013
• Study Type: interventional
• Target: 24
• 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. 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).

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

Outcome Measures

Primary Outcomes (2)

• 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

• Phase I: Maximum tolerated dose

  Phase I study: Determination of the maximum tolerated dose (MTD)

  Up to 9 months

Secondary Outcomes (12)

• Phase 0: Tumour-to-kidney radiation doses

  8 and 16 weeks

• Phase 0: Radiation doses

  8 and 16 weeks

• Phase 0: In vivo stability

  8 and 16 weeks

• Phase 0: Metabolites

  8 and 16 weeks

• Phase I: Side reactions

  8, 16 and 24 weeks

Study Arms (1)

Phase 0: One arm; Phase I: One arm

EXPERIMENTAL

Phase 0: 6 patients, intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N with and without Physiogel (crossover) Phase I: expected 12 - 18 patients, intravenous application of max. 6 x 7-8 GBq 177Lu-PP-F11N (increasing number of applications by one in groups of three patients). All patients with or without Physiogel, depending on the results of the phase 0 study.

Drug: 177Lu-PP-F11N

Interventions

177Lu-PP-F11N DRUG

Also known as: Minigastrin analogue, Gastrin analogue, Cholecystokinin-2 receptor ligand

Phase 0: One arm; Phase I: One arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

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 BACKGROUND

• 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.

  PMID: 31519804 BACKGROUND

Related Links

• Homepage University Hospital Basel

MeSH Terms

Conditions

Thyroid cancer, medullary; Carcinoma, Medullary; Neuroendocrine Tumors

Condition Hierarchy (Ancestors)

Carcinoma, Neuroendocrine; 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, Switzerland

  PRINCIPAL INVESTIGATOR

• Damian Wild, Prof Dr Dr

  University Hospital, Basel, Switzerland

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2014
• First Posted: March 17, 2014
• Study Start: April 1, 2015
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Locations

CH (1)