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

Sponsor
University Hospital, Basel, Switzerland (Other)
Overall Status
Completed
CT.gov ID
NCT03647657
Collaborator
Krebsforschung Schweiz, Bern, Switzerland (Other), Center for Proton Therapy, Paul Scherrer Institute, Villigen,Switzerland (Other), University Hospital, Zürich (Other), University Hospital Freiburg (Other)
8
Enrollment
1
Location
2
Arms
36
Actual Duration (Months)
0.2
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
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 Design

Study Type:
Interventional
Actual 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.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)
Actual Study Start Date :
Dec 13, 2018
Actual Primary Completion Date :
Dec 14, 2021
Actual Study Completion Date :
Dec 14, 2021

Arms and Interventions

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 Names:
  • Radiopharmakon

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

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Tumor radiation doses [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 [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 [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 [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 [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. Chromogranin A [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 [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

    Eligibility Criteria

    Criteria

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University Hospital Basel, Clinic for radiology and nuclear medicine Basel Switzerland 4031

    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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    University Hospital, Basel, Switzerland
    ClinicalTrials.gov Identifier:
    NCT03647657
    Other Study ID Numbers:
    • 2018-00972
    First Posted:
    Aug 27, 2018
    Last Update Posted:
    Feb 10, 2022
    Last Verified:
    Feb 1, 2022
    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 Neoplasms
    Thyroid Diseases
    Sacubitril and valsartan sodium hydrate drug combination

    Study Results

    No Results Posted as of Feb 10, 2022