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

Primary Purpose

Thyroid Cancer, Medullary, Neuroendocrine Tumor of the Lung Grade 1 and 2, Neuroendocrine Tumor of the Thymus Grade 1 and 2

Status

Recruiting

Phase

Phase 1

Locations

Switzerland

Study Type

Interventional

Intervention

177Lu-PP-F11N

About this trial

This is an interventional treatment trial for Thyroid Cancer, Medullary focused on measuring Calcitonin, Medullary thyroid carcinoma, Peptide receptor radionuclide therapy, Gastrin, Cholecystokinin-2 receptor, Neuroendocrine tumor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University Hospital Basel, Clinic for radiology and nuclear medicineRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Phase 0: One arm; Phase I: One arm

Arm Description

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.

Outcomes

Primary Outcome Measures

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).

Phase I: Maximum tolerated dose

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

Secondary Outcome Measures

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.

Phase 0: Radiation doses

Calculation of tumour and organ radiation doses.

Phase 0: In vivo stability

Evaluation of in vivo stability of 177Lu-PP-F11N.

Phase 0: Metabolites

Measurement of the metabolites of 177Lu-PP-F11N with and without Physiogel infusion.

Phase I: Side reactions

Evaluation of side reactions of 177Lu-PP-F11N.

Phase 1: Biochemical response

Evaluation of biochemical response (decrease of calcitonin and calculation of calcitonin doubling time).

Phase I: Morphological response

Evaluation of morphological therapy response (RECIST criteria).

Phase I: Tumour detection rate

Determination of the tumour detection rate and correlation with surgery/histology, if possible.

Phase I: Organ radiation doses

Calculation of organ radiation doses after therapy and correlation with the determined MTD (composite measure).

Phase 1: Overall survival

Determination of overall survival of patients after therapy.

Phase 1: In vivo stability

Evaluation of in vivo stability of 177Lu-PP-F11N.

Phase 1: Metabolites

Measurement of the metabolites of 177Lu-PP-F11N.

Full Information

NCT ID

NCT02088645

First Posted

February 19, 2014

Last Updated

May 23, 2022

Sponsor

University Hospital, Basel, Switzerland

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT02088645

Brief Title

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

Acronym

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.

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Recruiting

Study Start Date

April 2015 (undefined)

Primary Completion Date

June 2023 (Anticipated)

Study Completion Date

June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Basel, Switzerland

Collaborators

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

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Phase 0: One arm; Phase I: One arm

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

177Lu-PP-F11N

Other Intervention Name(s)

Minigastrin analogue, Gastrin analogue, Cholecystokinin-2 receptor ligand

Primary Outcome Measure Information:

Title

Phase 0: Scintigraphic visualisation rate

Description

Time Frame

up to 4 weeks

Title

Phase I: Maximum tolerated dose

Description

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

Time Frame

Up to 9 months

Secondary Outcome Measure Information:

Title

Phase 0: Tumour-to-kidney radiation doses

Description

Evaluation of the kidney radiation dose and the tumour-to-kidney radiation dose ratios with and without kidney protection (Physiogel). Composite measure.

Time Frame

8 and 16 weeks

Title

Phase 0: Radiation doses

Description

Calculation of tumour and organ radiation doses.

Time Frame

8 and 16 weeks

Title

Phase 0: In vivo stability

Description

Evaluation of in vivo stability of 177Lu-PP-F11N.

Time Frame

8 and 16 weeks

Title

Phase 0: Metabolites

Description

Measurement of the metabolites of 177Lu-PP-F11N with and without Physiogel infusion.

Time Frame

8 and 16 weeks

Title

Phase I: Side reactions

Description

Evaluation of side reactions of 177Lu-PP-F11N.

Time Frame

8, 16 and 24 weeks

Title

Phase 1: Biochemical response

Description

Evaluation of biochemical response (decrease of calcitonin and calculation of calcitonin doubling time).

Time Frame

For the duration of 24 months.

Title

Phase I: Morphological response

Description

Evaluation of morphological therapy response (RECIST criteria).

Time Frame

0, 3 and 12 months

Title

Phase I: Tumour detection rate

Description

Determination of the tumour detection rate and correlation with surgery/histology, if possible.

Time Frame

8, 16 and 24 weeks

Title

Phase I: Organ radiation doses

Description

Calculation of organ radiation doses after therapy and correlation with the determined MTD (composite measure).

Time Frame

8, 16 and 24 weeks

Title

Phase 1: Overall survival

Description

Determination of overall survival of patients after therapy.

Time Frame

Up to 5 years

Title

Phase 1: In vivo stability

Description

Evaluation of in vivo stability of 177Lu-PP-F11N.

Time Frame

8, 16 und 24 weeks

Title

Phase 1: Metabolites

Description

Measurement of the metabolites of 177Lu-PP-F11N.

Time Frame

8, 16 and 24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Christof Rottenburger, Dr. med.

Phone

0041613286551

Christof.Rottenburger@usb.ch

First Name & Middle Initial & Last Name or Official Title & Degree

Damian Wild, Prof Dr Dr

Phone

0041613286683

damian.wild@usb.ch

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Christof Rottenburger, Dr. med.

Organizational Affiliation

University Hospital, Basel, Switzerland

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Damian Wild, Prof Dr Dr

Organizational Affiliation

University Hospital, Basel, Switzerland

Official's Role

Study Director

Facility Information:

Facility Name

University Hospital Basel, Clinic for radiology and nuclear medicine

City

Basel

ZIP/Postal Code

4031

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Christof Rottenburger, Dr. med.

Phone

0041613286551

christof.rottenburger@ubs.ch

12. IPD Sharing Statement

Citations:

PubMed Identifier

30002107

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.

Results Reference

background

PubMed Identifier

31519804

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.

Results Reference

background

Links:

URL

https://www.unispital-basel.ch/en

Description

Homepage University Hospital Basel

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

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