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Completed

NCT Number: NCT03647657

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

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.

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Key information

Conditions

Thyroid Cancer, Medullary Adenocarcinoma Carcinoma Carcinoma, Medullary Carcinoma, Neuroendocrine Neoplasms Neoplasms by Histologic Type Neoplasms, Ductal, Lobular, and Medullary Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors

Age range

18 year–64 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

University Hospital Basel, Clinic for radiology and nuclear medicine

Basel, 4031, Switzerland

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

177Lu-PP-F11N

Drug

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

Other names: Radiopharmakon

Sacuitril

Drug

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

Other names: Entresto

Primary outcomes

  1. Tumor radiation doses

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

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

Secondary outcomes

  1. Kidney radiation doses

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

    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)

  2. Organ radiation doses

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

    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)

  3. In-vivo stability

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

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

  4. Autoradiography

    Time frame: Through study completion, up to 18 months

    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.

Other outcomes

  1. Chromogranin A

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

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

  2. 68Ga-DOTATOC PET/CT

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

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

Sponsors and collaborators

Lead sponsor

University Hospital, Basel, Switzerland

Other

Collaborators

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

Registry information

Official study title

177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer (Lumed Phase 0/B)

Important dates

Study start
2018
Primary completion
2021
Study completion
2021
First posted
Aug 27, 2018
Registry last updated
Feb 10, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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