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Metastatic Differentiated Thyroid CancerPhase 2131THEROPT124NCT05299437

Metastatic Thyroid Cancer Therapy Optimization With 124I PET Dosimetry

A Phase 2 study testing Radioiodine optimized therapy in people with Metastatic Differentiated Thyroid Cancer, run by Carlo Chiesa at 2 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Failure of conventional radioiodine therapy of metastatic differentiated thyroid cancer could be explained by: a suboptimal therapeutic approach, based on the administration of empirically fixed amount of radioactivity the presence of lesions with impaired iodine uptake, due to the expression of specific mutations The… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Differentiated Thyroid Cancer
What is being tested?
Radioiodine optimized therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
2 sitesItaly
Study dates
12 May 2021to 30 Sep 2024
Phase
Phase 2
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histo-pathological diagnosis of DTC
  • At least one documented non surgically-curable soft-tissue metastasis previously untreated
  • ECOG performance status = 0 - 1
  • Life expectancy > 6 months
  • Females of childbearing age must have negative serum pregnancy test prior to registration and agree to use birth control throughout the study and for 6 months after completion of therapy
  • Preserved hematologic and renal function (hemoglobin > 10 g/dL; WBC > 3500/uL; neutrophils > 50%; PLT > 100000/uL; albumin ≥ 2.5 g/dL; creatinine ≤ 2 mg/dL)
  • Signed informed consent

Who cannot join

  • All lesions surgically resectable
  • Minimal lymph nodal disease (diameter < 1 cm, up to 2 nodes)
  • Patient with skeletal metastases only
  • Lung diffuse miliary micro-metastases
  • Ongoing pregnancy
  • Breast-feeding (enrollment could be considered after suspension)
Show all 14Show fewer
  • Refusal of male and female patients to use an effective contraception method during the study and for 6 months after completion of protocol therapy
  • Impossibility to undergo follow-up procedures
  • Presence of medical, psychiatric or surgical condition, not adequately controlled by treatment, which would likely affect subjects' ability to complete the protocol
  • Assumption of any anti-tumor therapy including chemotherapy, biological or investigational drug treatments
  • Assumption of any myelotoxic drugs
  • Previous or concomitant assumption of Amiodarone
  • Any other oncologic disease that required treatment in the last 5 years.
  • Participation in a clinical trial in which an investigational drug was administered within 30 days or 5 half-lives prior to the study drug.

Trial locations and contacts

2 sites in 1 country.

Ettore Seregni, MD contact

+39 02 2390 ext. 3320

ettore.seregni@istitutotumori.mi.it

Daria Scienza, MD contact

+39 02 2390 ext. 2220

daria.scienza@istitutotumori.mi.it

Italy2 sites, 2 recruiting

  • Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori

    Milan, 20133

    Marco Maccauro, MD, +39 02 2390 ext. 2510, marco.maccauro@istitutotumori.mi.it

    Valentina Fuoco, MD, +39 02 2390 ext. 3887, valentina.fuoco@istitutotumori.mi.it

    Recruiting

  • Nuclear Medicine, Ospedale Sacro Cuore - Don Calabria

    Negrar, Verona, 37129

    Matteo Salgarello, MD, +39 045 601 ext. 4611, matteo.salgarello@sacrocuore.it

    Laura Olivari, MD, +39 333 1885362, laura.olivari@sacrocuore.it

    Recruiting

Other trials in Italy

About this study

Official title: Personalized Therapy of Metastatic Thyroid Cancer: Biological Characterization and Optimization With 124I PET Dosimetry

Failure of conventional radioiodine therapy of metastatic differentiated thyroid cancer could be explained by:

  • a suboptimal therapeutic approach, based on the administration of empirically fixed amount of radioactivity
  • the presence of lesions with impaired iodine uptake, due to the expression of specific mutations

The study aims to:

  • optimize therapy with pre-treatment 124-I blood and lesion dosimetry
  • collect genetic data to check if specific mutations and/or miRNA over-expression could be related to low iodine uptake or to radioresistance
Read the detailed description

TRIAL DESIGN

This is a one-stage, phase II, single-arm, bi-centric study. Enrollment centres are the Istituto Nazionale Tumori in Milan, and the Sacro Cuore Don Calabria Hospital in Negrar, close to Verona. Both centres are located in North Italy. 124-I is produced by cyclotron in Negrar Radiopharmacy unit, while high-activity 131-I therapy will be delivered in Milan.

Patients with ascertained metastatic differentiated thyroid cancer are studied with FDG PET and CT. 124-I blood and lesion PET dosimetry is used to optimize the 131-I therapeutic activity. The same 124-I PET scans are repeated 6 months after therapy as response assessment. 124-I and 131-I administration are performed after hormon withdrawal.

Primary tumour tissue and circulating miRNA will be analyzed to check the genetical features.

According to 124-I dosimetric PET data published by Jentzen et al, good efficacy (Tumour Control Probability > 80%) is obtained with absorbed dose > 80 Gy to soft tissue metastases, and > 650 Gy to bone metastases. Seen this difference, only soft tissue lesions are considered as target for the calculation of the complete response rate.

However, for ethical reasons, therapeutic activity will be chosen in order to be effective both on soft tissue and bone lesions. Patients with too low predicted lesion absorbed dose even administering the Maximum Tolerable Activity (2 Gy to blood) will exit the protocol to receive the standard of care.

PRIMARY END-POINT

Evaluation of complete response (CR) rate on soft tissue metastases 6 months after treatment, or later. The best response will be considered.

SECONDARY END-POINTS

Assessment of:

  • acute toxicity rate and severity
  • the association among pre-treatment glucose metabolism, 124-I uptake and therapy response
  • the association among genetic mutations (BRAF V600E, TERT promoter, others) on thyroid cancer tissue, pre- and post-treatment miRNA expression, pre- and post-treatment glucose metabolism, iodine uptake, and 131-I therapy response

SAMPLE SIZE AND POPULATION

By considering a complete response (CR) rate in patients of soft tissue metastases after fixed activity approach as published by Klubo-Gwiezdzinska et al and by assuming an increment of 15% in CR rate after dosimetry-based administration, 46 evaluable patients will be required to test the above hypotheses.

Being tested
Radioiodine optimized therapy
Keywords
Thyroid cancer, dosimetry, 124-I, therapy optimization
Medical subject headings
Thyroid Neoplasms

What participants receive

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

  • Radioiodine optimized therapyDrug

    124-I blood and lesion dosimetry will be used to optimize the 131-I therapeutic activity. Both 124-I and 131-I administration will be performed after hormon withdrawal.

    Primary tumour tissue and circulating miRNA will be analyzed to check the genetic status.

Study groups in NCT05299437
Study groupRoleWhat they receive
Optimized therapyExperimentalPatients with ascertained metastatic differentiated thyroid cancer will be studied with FDG PET, CT, and for genetic characterization. 100 MBq of 124-I are administered for blood and PET lesion dosimetry. According Jentzen et al, good efficacy (Tumour Control Probability > 80%) is obtained with absorbed dose higher than 80 Gy to soft tissue metastases, and > 650 Gy to bone metastases. These values ae pursued with the limit of 2 Gy to blood. Only soft tissue lesions will be considered as target for the calculation of the complete response rate. However, for ethical reasons, therapeutic activity will be chosen in order to be effective both on soft tissue and bone lesions. Patients with too low predicted lesion absorbed dose even administering the Maximum Tolerable Activity (2 Gy to blood) will exit the protocol to receive the standard of care.
Receives: Drug: Radioiodine optimized therapy

What is being measured

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

  1. Response

    Evaluation of complete response (CR) rate on soft tissue metastases 6 months after treatment, or later. The best response will be considered.

    RECIST 1.1 Evaluation of the best response rate on soft tissue metastases

    Measured: 6 months, repeated through study completion, an average of 2 year

Secondary outcomes (5)

  1. Association between presence/absence of metastatic pre-treatment FDG uptake and response

    Statistical tests will be applied to test the significance of the association.

    Measured: 6 months, repeated through study completion, for an average of 2 year

  2. Association between the presence/absence of specific mutations in neoplastic thyroid tissue and response

    Statistical tests will be applied to test the significance of the association.

    Measured: 6 months, repeated through study completion, for an average of 2 year

  3. Association between circulating miRNA deregulation and response

    Statistical tests will be applied to test the significance of the association.

    Measured: 6 months, repeated through study completion, for an average of 2 years

  4. Progression Free Survival interval (PFS) [months] from the first iodine treatment.

    PFS will be assessed according to the standard clinical practice

    Measured: every 6 months or more frequently, through study completion, for an average of 2 years

  5. Overall Survival [months] from the first iodine treatment.

    Survival status will be collected

    Measured: At the end of the study, an average of 2 years

Timeline

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

  1. First posted29 Mar 2022
  2. Study start12 May 2021
  3. Primary completion30 Mar 2024 (estimated)
  4. Study completion30 Sep 2024 (estimated)

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
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05299437
Sponsor's protocol ID
AIRC 21939
Acronym
131THEROPT124
Status last verified
Mar 2022
First submitted
7 Mar 2022
Last updated
29 Mar 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Klubo-Gwiezdzinska J, Van Nostrand D, Atkins F, Burman K, Jonklaas J, Mete M, Wartofsky L. Efficacy of dosimetric versus empiric prescribed activity of 131I for therapy of differentiated thyroid cancer. J Clin Endocrinol Metab. 2011 Oct;96(10):3217-25. doi: 10.1210/jc.2011-0494. Epub 2011 Aug 17.

    PubMed 21849530

  • Nagarajah J, Janssen M, Hetkamp P, Jentzen W. Iodine Symporter Targeting with 124I/131I Theranostics. J Nucl Med. 2017 Sep;58(Suppl 2):34S-38S. doi: 10.2967/jnumed.116.186866.

    PubMed 28864610

  • Jentzen W, Verschure F, van Zon A, van de Kolk R, Wierts R, Schmitz J, Bockisch A, Binse I. 124I PET Assessment of Response of Bone Metastases to Initial Radioiodine Treatment of Differentiated Thyroid Cancer. J Nucl Med. 2016 Oct;57(10):1499-1504. doi: 10.2967/jnumed.115.170571. Epub 2016 May 19.

    PubMed 27199362

  • Jentzen W, Hoppenbrouwers J, van Leeuwen P, van der Velden D, van de Kolk R, Poeppel TD, Nagarajah J, Brandau W, Bockisch A, Rosenbaum-Krumme S. Assessment of lesion response in the initial radioiodine treatment of differentiated thyroid cancer using 124I PET imaging. J Nucl Med. 2014 Nov;55(11):1759-65. doi: 10.2967/jnumed.114.144089. Epub 2014 Oct 20.

    PubMed 25332440

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Radioiodine optimized therapy in people with Metastatic Differentiated Thyroid Cancer, run by Carlo Chiesa at 2 sites in Italy.

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 7 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 29 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Italy. 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?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Results are not available in the source record.

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

Contact Ettore Seregni, MD (+39 02 2390 ext. 3320, ettore.seregni@istitutotumori.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response (time frame: 6 months, repeated through study completion, an average of 2 year). 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 NCT05299437, which also lists 4 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 29 Mar 2022.

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