The Use of 124-I-PET/CT Whole Body and Lesional Dosimetry in Differentiated Thyroid Cancer

NCT ID: NCT03841617

Last Updated: 2025-12-26

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

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-07-29

Study Completion Date

2035-11-01

Brief Summary

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Study rationale

High risk patients with differentiated thyroid cancer (DTC) require therapy with 131 I under thyroid stimulating hormone (TSH) stimulation. There are two methods of TSH stimulation endogenous by thyroid hormone withdrawal (THW) leading to hypothyroidism and exogenous by injection of human recombinant TSH (rhTSH Thyrogen). The appropriate 131-I activity utilized for treatment is either based on empiric fixed dosage choice or individually determined activity based on 131 I dosimetric calculations. Although dosimetry utilizing radioactive iodine isotope 131 I enables calculation of maximum safe dose, it does not estimate the tumoricidal activity necessary to destroy the metastatic lesions. The alternative radioactive isotope of iodine -124 I, used for positron emission tomography (PET) imaging, might be used for calculation not only the maximum safe131 I dose, but also to predict the absorbed dose in the metastatic lesions.

Study objectives

The primary objective of this study is to compare the 124 I -PET/CT lesional and whole body dosimetry in each individual patient with metastatic radioiodine (RAI)-avid thyroid cancer under preparation with rhTSH and THW. The secondary objective is to evaluate the predicted by PET/CT lesional uptake with the early response to therapy.

Study design

This is a phase 2 pilot prospective cohort study comparing the lesional and whole body dosimetry within each patient undergoing exogenous (rhTSH) and endogenous (THW) TSH stimulation and followed for 5 years.

Interventions

Each study participant will undergo rhTSH and THW-aided 124 I-PET/CT dosimetric evaluations and will be subsequently treated with THW-aided RAI activity based on dosimetric calculations enabling maximum safe dosage. The patients will be followed in 12+/-3 months intervals for 5 years.

Sample size and population

This pilot study will include 30 patients with high risk differentiated thyroid cancer presenting with distant and/or loco-regional metastases.

Detailed Description

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Study Description:

Each study participant will undergo rhTSH and THW-aided 124IPET/ CT dosimetric evaluations and will be subsequently treated with THW-aided RAI activity based on dosimetric calculations enabling maximum safe dosage.

Objectives:

Primary objective: To compare the 124I -PET/CT lesional and whole body dosimetry in each individual patient with metastatic radioiodine (RAI)-avid thyroid cancer under preparation with rhTSH and THW.

Secondary objective: To evaluate the predicted by PET/CT lesional uptake with the early response to therapy.

Endpoints:

Primary Endpoint: The predicted radiation dose measured as rads per lesion compared per each measurable lesion between the dose calculated under rhTSH and under THW.

Secondary Endpoints: Area under the curve analyzing the association of dose per lesion measured in rads and objective response to treatment at 1, 2, 3, 4, 5 years landmarks.

Conditions

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Thyroid Cancer

Keywords

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Thyroid Cancer PET/CT 124-I Radioiodine Metastases

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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124I PET/CT scan after rhTSH

124I PET/CT scan after preparation with human recombinant TSH

Group Type ACTIVE_COMPARATOR

Thyrogen

Intervention Type DRUG

intramuscular injection administered once/day for 2 consecutive days at Week 3; then once annually for subjects who meet criteria.

I-131

Intervention Type RADIATION

therapeutic dose administered orally to treat thyroid cancer at Week 8. 5-7 days later, the post-treatment I-131 Whole Body scan w/ SPECT is performed; then administered once annually, if the patient needs to be re-treated

I-124

Intervention Type RADIATION

one capsule ingested orally once at Week 3, and Week 8; then administered once annually to subjects who meet criteria.

124I PET/CT scan after thyroid hormone withdrawal

124I PET/CT scan after preparation with thyroid hormone withdrawal

Group Type ACTIVE_COMPARATOR

I-131

Intervention Type RADIATION

therapeutic dose administered orally to treat thyroid cancer at Week 8. 5-7 days later, the post-treatment I-131 Whole Body scan w/ SPECT is performed; then administered once annually, if the patient needs to be re-treated

I-124

Intervention Type RADIATION

one capsule ingested orally once at Week 3, and Week 8; then administered once annually to subjects who meet criteria.

Thyroid hormone withdrawal

Intervention Type OTHER

withdrawal of thyroid hormone during weeks 4 through 8

Interventions

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Thyrogen

intramuscular injection administered once/day for 2 consecutive days at Week 3; then once annually for subjects who meet criteria.

Intervention Type DRUG

I-131

therapeutic dose administered orally to treat thyroid cancer at Week 8. 5-7 days later, the post-treatment I-131 Whole Body scan w/ SPECT is performed; then administered once annually, if the patient needs to be re-treated

Intervention Type RADIATION

I-124

one capsule ingested orally once at Week 3, and Week 8; then administered once annually to subjects who meet criteria.

Intervention Type RADIATION

Thyroid hormone withdrawal

withdrawal of thyroid hormone during weeks 4 through 8

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Patients with established thyroid cancer diagnosis based on the pathology report reviewed at the National Institutes of Health, who:

* underwent total thyroidectomy plus or minus neck lymph node dissection as clinically indicated,
* are presenting with known per structural imaging (US neck, CT or MRI neck/chest/abdomen/pelvis) persistent/recurrent disease either locally advanced or presenting with distant metastases; or
* are presenting with suspected persistent/recurrent locoregional or distant metastases based on the high risk features such as advanced tumor per pathology report (tumor size \>4 cm, exrathyroidal extension, higher risk pathology such as tall cell, columnar cell, poorly differentiated variant, follicular thyroid cancer with gross vascular invasion, positive margins after the surgery, bulky lymphadenopathy in the central and/or lateral neck), detectable/increasing baseline/suppressed thyroglobulin (Tg) level or detectable/increasing anti-Tg antibody titers if anti-Tg antibodies are present.
* are either RAI -naive or requiring repeated RAI therapy for locally advanced disease or distant metastases or underwent therapy with BRAF inhibitor (dabrafenib or vemurafenib\*) or selumetinib\*\* for at least 4 weeks that may re-induce RAI uptake.
* Underwent imaging with either a CT or MRI of the brain and spine with gadolinium contrast to screen for the brain/spine metastases.

* Age greater than or equal to 18 years of age.
* 24 hour urine iodine excretion of less than or equal to 150 micro grams/24 hour.

* BRAF inhibitors are recommended by 2021 NCCN guidelines as one of the management options for BRAF mutant tumors(13,14)

* Selumetinib has an FDA orphan drug designation for adjuvant treatment of metastatic thyroid cancer to re-induce RAI uptake

Exclusion Criteria

-Patients with RAI-non avid disease documented by negative post-therapy whole body scans performed after previous RAI treatments and not subjected to re-differentiation therapy.

* Serious underlying medical conditions that restrict diagnostic testing or therapy such as renal failure, congestive cardiac failure or active coexisting non-thyroid carcinoma, severe depression which might be exacerbated by thyroid hormone withdrawal.
* Patients with spinal or brain metastases as they are at risk of TSH-stimulation induced swelling of metastatic lesions leading to potentially detrimental side effects. These patients will be evaluated per the standard of care protocol 77-DK-0096.

* Pregnant or lactating women per self report.
* Adults who are incapable of providing informed consent.
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Joanna Klubo-Gwiezdzinska, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Locations

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National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Padmasree Veeraraghavan, R.N.

Role: CONTACT

Phone: (301) 451-7710

Email: [email protected]

Joanna Klubo-Gwiezdzinska, M.D.

Role: CONTACT

Phone: (301) 496-5052

Email: [email protected]

Facility Contacts

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For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Role: primary

Related Links

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Other Identifiers

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19-DK-0050

Identifier Type: -

Identifier Source: secondary_id

190050

Identifier Type: -

Identifier Source: org_study_id