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177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer

Primary Purpose

Thyroid Cancer, Medullary

Status

Completed

Phase

Early Phase 1

Locations

Switzerland

Study Type

Interventional

Intervention

177Lu-PP-F11N

Sacuitril

About this trial

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

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University Hospital Basel, Clinic for radiology and nuclear medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Entresto second

Entresto first

Arm Description

First intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N without and second injection with additional medication of Sacuitril (100 mg Entresto)(crossover)

First intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N with and second injection without additional medication of Sacuitril (100 mg Entresto)(crossover)

Outcomes

Primary Outcome Measures

Tumor radiation doses

Evaluation of the radiation doses in tumor tissue from MTC after injection of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto)

Secondary Outcome Measures

Kidney radiation doses

Evaluation of the radiation doses in the kidneys and the tumor-to-kidney dose ratios after injection of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto)

Organ radiation doses

Evaluation of the radiation doses in other organs and the appropriate organ-to-kidney dose ratios after injection of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto)

In-vivo stability

Measurement (HPLC) of the in-vivo stability of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto).

Autoradiography

In case of surgery with available tumor tissue samples, imaging results will be compared with autoradiographic analysis of somatostatine- and CCK2-receptor expression in tumor tissue.

Full Information

NCT ID

NCT03647657

First Posted

August 20, 2018

Last Updated

February 9, 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

NCT03647657

Brief Title

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

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Completed

Study Start Date

December 13, 2018 (Actual)

Primary Completion Date

December 14, 2021 (Actual)

Study Completion Date

December 14, 2021 (Actual)

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

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

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.

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.

6. Conditions and Keywords

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

Thyroid Cancer, Medullary

Keywords

Calcitonin, Medullary thyroid carcinoma, Peptide receptor radionuclide therapy, Gastrin, Cholecystokinin-2 receptor

7. Study Design

Primary Purpose

Basic Science

Study Phase

Early Phase 1

Interventional Study Model

Crossover Assignment

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.

Masking

None (Open Label)

Masking Description

No masking

Allocation

Randomized

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Entresto second

Arm Type

Experimental

Arm Description

First intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N without and second injection with additional medication of Sacuitril (100 mg Entresto)(crossover)

Arm Title

Entresto first

Arm Type

Experimental

Arm Description

First intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N with and second injection without additional medication of Sacuitril (100 mg Entresto)(crossover)

Intervention Type

Drug

Intervention Name(s)

177Lu-PP-F11N

Other Intervention Name(s)

Radiopharmakon

Intervention Description

Intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N with and without co-medication with Sacuitril (100 mg Entresto) in each patient

Intervention Type

Drug

Intervention Name(s)

Sacuitril

Other Intervention Name(s)

Entresto

Intervention Description

Medication with Sacuitril (100 mg Entresto) additional to the injection of 177Lu-PP-F11N

Primary Outcome Measure Information:

Title

Tumor radiation doses

Description

Evaluation of the radiation doses in tumor tissue from MTC after injection of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto)

Time Frame

Measurement up to 72 hours after each injection of 177Lu-PP-F11N

Secondary Outcome Measure Information:

Title

Kidney radiation doses

Description

Evaluation of the radiation doses in the kidneys and the tumor-to-kidney dose ratios after injection of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto)

Time Frame

Measurement up to 72 hours after each injection of 177Lu-PP-F11N

Title

Organ radiation doses

Description

Evaluation of the radiation doses in other organs and the appropriate organ-to-kidney dose ratios after injection of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto)

Time Frame

Measurement up to 72 hours after each injection of 177Lu-PP-F11N

Title

In-vivo stability

Description

Measurement (HPLC) of the in-vivo stability of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto).

Time Frame

Blood samples for measurement 5 and 30 minutes post injection of 177Lu-PP-F11N

Title

Autoradiography

Description

In case of surgery with available tumor tissue samples, imaging results will be compared with autoradiographic analysis of somatostatine- and CCK2-receptor expression in tumor tissue.

Time Frame

Through study completion, up to 18 months

Other Pre-specified Outcome Measures:

Title

Chromogranin A

Description

Chromogranin A blood values will be compared to the radiation doses of the stomach.

Time Frame

Measurement up to 72 hours after the first injection of 177Lu-PP-F11N

Title

68Ga-DOTATOC PET/CT

Description

Comparison of tumor imaging by 68Ga-DOTATOC PET/CT and 177Lu-PP-F11N SPECT/CT

Time Frame

Measurement up to 72 hours after each injection of 177Lu-PP-F11N

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Christof Rottenburger, Dr. med.

Organizational Affiliation

University Hospital Basel, Clinic for radiology and nuclear medicine

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Damian Wild, PhD Dr

Organizational Affiliation

University Hospital Basel, Clinic for radiology and nuclear medicine

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

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

result

Links:

URL

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

Description

University Hospital Basel Homepage

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177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer

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