A Phase 2 interventional study of Thyrogen and I-131 in Thyroid Cancer, sponsored by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Recruiting at 1 site in United States. Open to participants aged 18 Years to 90 Years. Per ClinicalTrials.gov, last updated 2026-09-09.
Sponsored by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) · Phase 2, Interventional, and Treatment
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.
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.
Patients with established thyroid cancer diagnosis based on the pathology report reviewed at the National Institutes of Health, who:
Underwent imaging with either a CT or MRI of the brain and spine with gadolinium contrast to screen for the brain/spine metastases.
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)
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.
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.
124I PET/CT scan after preparation with human recombinant TSH
Drug: Thyrogen · Radiation: I-131 · Radiation: I-124
124I PET/CT scan after preparation with thyroid hormone withdrawal
Radiation: I-131 · Radiation: I-124 · Other: Thyroid hormone withdrawal
intramuscular injection administered once/day for 2 consecutive days at Week 3; then once annually for subjects who meet criteria.
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
one capsule ingested orally once at Week 3, and Week 8; then administered once annually to subjects who meet criteria.
withdrawal of thyroid hormone during weeks 4 through 8
Comparison of the whole body and lesional 124I uptake within each patient prepared for imaging with human recombinant TSH (rhTSH) and thyroid hormone withdrawal (THW)
Whole body and lesional uptake of 124I calculated after preparation with human recombinant TSH (rhTSH) compared to dosimetry calculated after preparation using thyroid hormone withdrawal (THW)
Time frame: 9 weeks
Plan to share: No — Subject level data will be shared upon request after appropriate collaboration agreements are in place.
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)