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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 : Recruiting
First Posted : August 27, 2018
Last Update Posted : July 22, 2020
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

Tracking Information
First Submitted Date  ICMJE August 20, 2018
First Posted Date  ICMJE August 27, 2018
Last Update Posted Date July 22, 2020
Actual Study Start Date  ICMJE December 13, 2018
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 22, 2018)
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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 22, 2018)
  • 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)
  • 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)
  • 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).
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 20, 2020)
  • 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.
  • 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
Original Other Pre-specified Outcome Measures
 (submitted: August 22, 2018)
  • 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.
  • 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
 
Descriptive Information
Brief Title  ICMJE 177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer
Official Title  ICMJE 177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer (Lumed Phase 0/B)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE 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
Condition  ICMJE Thyroid Cancer, Medullary
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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)
    Interventions:
    • Drug: 177Lu-PP-F11N
    • Drug: Sacuitril
  • 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)
    Interventions:
    • Drug: 177Lu-PP-F11N
    • Drug: Sacuitril
Publications * Sauter AW, Mansi R, Hassiepen U, Muller L, Panigada T, Wiehr S, Wild AM, Geistlich S, Béhé M, Rottenburger C, Wild D, Fani M. Targeting of the Cholecystokinin-2 Receptor with the Minigastrin Analog (177)Lu-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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 22, 2018)
8
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2021
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 64 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Christof Rottenburger, Dr. med. 0041613286551 christof.rottenburger@usb.ch
Contact: Damian Wild, PhD Dr 0041613286683 damian.wild@usb.ch
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03647657
Other Study ID Numbers  ICMJE 2018-00972
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Hospital, Basel, Switzerland
Study Sponsor  ICMJE University Hospital, Basel, Switzerland
Collaborators  ICMJE
  • Krebsforschung Schweiz, Bern, Switzerland
  • Center for Proton Therapy, Paul Scherrer Institute, Villigen,Switzerland
  • University Hospital, Zürich
  • University Hospital Freiburg
Investigators  ICMJE
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
PRS Account University Hospital, Basel, Switzerland
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP