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Thyroid Cancer, MedullaryEarly Phase 1NCT03647657

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

A Early Phase 1 study testing 177Lu-PP-F11N and Sacuitril in people with Thyroid Cancer, Medullary, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 64 years
Conditions the study is for
Thyroid Cancer, Medullary
What is being tested?
177Lu-PP-F11N and Sacuitril
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteSwitzerland
Study dates
13 Dec 2018to 14 Dec 2021
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Switzerland1 site

  • University Hospital Basel, Clinic for radiology and nuclear medicine

    Basel, 4031

Other trials in Switzerland

About this study

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

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.

Read the 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.

Being tested
177Lu-PP-F11N, Sacuitril
Keywords
Calcitonin, Medullary thyroid carcinoma, Peptide receptor radionuclide therapy, Gastrin, Cholecystokinin-2 receptor
Medical subject headings
Thyroid cancer, medullary, Carcinoma, Medullary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 177Lu-PP-F11NDrug

    Also called Radiopharmakon

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

  • SacuitrilDrug

    Also called Entresto

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

Study groups in NCT03647657
Study groupRoleWhat they receive
Entresto secondExperimentalFirst intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N without and second injection with additional medication of Sacuitril (100 mg Entresto)(crossover)
Receives: Drug: 177Lu-PP-F11N; Drug: Sacuitril
Entresto firstExperimentalFirst intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N with and second injection without additional medication of Sacuitril (100 mg Entresto)(crossover)
Receives: Drug: 177Lu-PP-F11N; Drug: Sacuitril

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

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

Secondary outcomes (4)

  1. 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)

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

  2. 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)

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

  3. In-vivo stability

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

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

  4. 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.

    Measured: Through study completion, up to 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Aug 2018
  2. Study start13 Dec 2018
  3. Primary completion14 Dec 2021
  4. Study completion14 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
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)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03647657
Sponsor's protocol ID
2018-00972
Other IDs
2018
Status last verified
Feb 2022
First submitted
20 Aug 2018
Last updated
10 Feb 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 30002107

  • Rottenburger C, Hentschel M, Furstner M, McDougall L, Kottoros D, Kaul F, Mansi R, Fani M, Vija AH, Schibli R, Geistlich S, Behe M, Christ ER, Wild D. In-vivo inhibition of neutral endopeptidase 1 results in higher absorbed tumor doses of [177Lu]Lu-PP-F11N in humans: the lumed phase 0b study. EJNMMI Res. 2024 Apr 6;14(1):37. doi: 10.1186/s13550-024-01101-w.

    PubMed 38581480

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing 177Lu-PP-F11N and Sacuitril in people with Thyroid Cancer, Medullary, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Tumor radiation doses (time frame: Measurement up to 72 hours after each injection of 177Lu-PP-F11N). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03647657, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2022.

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