Metastatic Thyroid Cancer Therapy Optimization With 124I PET Dosimetry

NCT05299437 | Unknown Phase 2 DMC

• 1 other identifier: AIRC 21939
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief 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 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

Conditions

Metastatic Differentiated Thyroid Cancer

Keywords

Thyroid cancer, dosimetry, 124-I, therapy optimization

Outcome Measures

Primary Outcomes (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

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

Secondary Outcomes (5)

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

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

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

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

• Association between circulating miRNA deregulation and response

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

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

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

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

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

Other Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Through study completion, an average of 2 years

Study Arms (1)

Optimized therapy

EXPERIMENTAL

Patients 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.

Drug: Radioiodine optimized therapy

Interventions

Radioiodine optimized therapy DRUG

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.

Optimized therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• Carlo Chiesa: lead
• Associazione Italiana per la Ricerca sul Cancro: collaborator

Study Sites (2)

Nuclear Medicine, Ospedale Sacro Cuore - Don Calabria

Negrar, Verona, 37129, Italy

RECRUITING

Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori

Milan, 20133, Italy

RECRUITING

Related Publications (4)

• 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.

  PMID: 21849530 BACKGROUND

• 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.

  PMID: 28864610 BACKGROUND

• 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.

  PMID: 27199362 BACKGROUND

• 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.

  PMID: 25332440 BACKGROUND

MeSH Terms

Conditions

Thyroid Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Study Officials

• Carlo Chiesa, PhD

  Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ettore Seregni, MD

CONTACT

+39 02 2390; ettore.seregni@istitutotumori.mi.it

Daria Scienza, MD

CONTACT

+39 02 2390; daria.scienza@istitutotumori.mi.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Physics Expert

Study Record Dates

• First Submitted: March 7, 2022
• First Posted: March 29, 2022
• Study Start: May 12, 2021
• Primary Completion: March 30, 2024
• Study Completion: September 30, 2024
• Last Updated: March 29, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)