Metastatic Thyroid Cancer Therapy Optimization With 124I PET Dosimetry

NCT ID: NCT05299437

Last Updated: 2022-03-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-12

Study Completion Date

2024-09-30

Brief Summary

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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

Detailed Description

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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.

Conditions

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Metastatic Differentiated Thyroid Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Optimized therapy

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.

Group Type EXPERIMENTAL

Radioiodine optimized therapy

Intervention Type 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.

Interventions

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Radioiodine optimized therapy

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Associazione Italiana per la Ricerca sul Cancro

OTHER

Sponsor Role collaborator

Carlo Chiesa

OTHER

Sponsor Role lead

Responsible Party

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Carlo Chiesa

Medical Physics Expert

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Carlo Chiesa, PhD

Role: PRINCIPAL_INVESTIGATOR

Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori

Locations

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Nuclear Medicine, Ospedale Sacro Cuore - Don Calabria

Negrar, Verona, Italy

Site Status RECRUITING

Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori

Milan, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Ettore Seregni, MD

Role: CONTACT

+39 02 2390 ext. 3320

Daria Scienza, MD

Role: CONTACT

+39 02 2390 ext. 2220

Facility Contacts

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Matteo Salgarello, MD

Role: primary

+39 045 601 ext. 4611

Laura Olivari, MD

Role: backup

+39 333 1885362

Marco Maccauro, MD

Role: primary

+39 02 2390 ext. 2510

Valentina Fuoco, MD

Role: backup

+39 02 2390 ext. 3887

References

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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.

Reference Type BACKGROUND
PMID: 21849530 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28864610 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27199362 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25332440 (View on PubMed)

Other Identifiers

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AIRC 21939

Identifier Type: -

Identifier Source: org_study_id

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