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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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ClinicalTrials.gov Identifier: NCT03647657
Recruitment Status : Not yet recruiting
First Posted : August 27, 2018
Last Update Posted : November 7, 2018
Sponsor:
Collaborators:
Krebsforschung Schweiz, Bern, Switzerland
Center for Proton Therapy, Paul Scherrer Institute, Villigen,Switzerland
University Hospital, Zürich
University Hospital Freiburg
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

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.

Condition or disease Intervention/treatment Phase
Thyroid Cancer, Medullary Drug: 177Lu-PP-F11N Drug: Sacuitril Early Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention 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
Primary Purpose: Basic Science
Official Title: 177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer (Lumed Phase 0/B)
Estimated Study Start Date : December 2018
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : October 2020


Arm Intervention/treatment
Experimental: Entresto second
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)
Drug: 177Lu-PP-F11N
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 Name: Radiopharmakon

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

Experimental: Entresto first
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)
Drug: 177Lu-PP-F11N
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 Name: Radiopharmakon

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




Primary Outcome Measures :
  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 Outcome Measures :
  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 Outcome Measures:
  1. Chromogranine A [ Time Frame: Measurement up to 72 hours after the first injection of 177Lu-PP-F11N ]
    Chromogranine 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



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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03647657


Contacts
Contact: Christof Rottenburger, Dr. med. 0041613286551 christof.Rottenburger@usb.ch
Contact: Damian Wild, PhD Dr 0041613286683 damian.wild@usb.ch

Sponsors and Collaborators
University Hospital, Basel, Switzerland
Krebsforschung Schweiz, Bern, Switzerland
Center for Proton Therapy, Paul Scherrer Institute, Villigen,Switzerland
University Hospital, Zürich
University Hospital Freiburg
Investigators
Principal Investigator: Christof Rottenburger, Dr. med. University Hospital Basel, Clinic for radiology and nuclear medicine
Study Director: Damian Wild, PhD Dr University Hospital Basel, Clinic for radiology and nuclear medicine

Additional Information:
Publications of Results:
Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT03647657     History of Changes
Other Study ID Numbers: 2018-00972
First Posted: August 27, 2018    Key Record Dates
Last Update Posted: November 7, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Basel, Switzerland:
Calcitonin
Medullary thyroid carcinoma
Peptide receptor radionuclide therapy
Gastrin
Cholecystokinin-2 receptor

Additional relevant MeSH terms:
Thyroid Diseases
Thyroid Neoplasms
Carcinoma, Neuroendocrine
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
LCZ 696
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action