NCT03841617

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_2

Timeline
116mo left

Started Jul 2019

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress42%
Jul 2019Nov 2035

First Submitted

Initial submission to the registry

February 13, 2019

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 15, 2019

Completed
5 months until next milestone

Study Start

First participant enrolled

July 29, 2019

Completed
16.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2035

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2035

Last Updated

April 20, 2026

Status Verified

April 2, 2026

Enrollment Period

16.3 years

First QC Date

February 13, 2019

Last Update Submit

April 17, 2026

Conditions

Keywords

Thyroid CancerPET/CT124-IRadioiodineMetastases

Outcome Measures

Primary Outcomes (1)

  • 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)

    9 weeks

Study Arms (2)

124I PET/CT scan after rhTSH

ACTIVE COMPARATOR

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

Drug: ThyrogenRadiation: I-131Radiation: I-124

124I PET/CT scan after thyroid hormone withdrawal

ACTIVE COMPARATOR

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

Radiation: I-131Radiation: I-124Other: Thyroid hormone withdrawal

Interventions

I-131RADIATION

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

124I PET/CT scan after rhTSH124I PET/CT scan after thyroid hormone withdrawal

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

124I PET/CT scan after rhTSH
I-124RADIATION

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 rhTSH124I PET/CT scan after thyroid hormone withdrawal

withdrawal of thyroid hormone during weeks 4 through 8

124I PET/CT scan after thyroid hormone withdrawal

Eligibility Criteria

Age18 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

MeSH Terms

Conditions

Thyroid NeoplasmsNeoplasm Metastasis

Interventions

Thyrotropin AlfaIodine-131Iodine-124

Condition Hierarchy (Ancestors)

Endocrine Gland NeoplasmsNeoplasms by SiteNeoplasmsHead and Neck NeoplasmsEndocrine System DiseasesThyroid DiseasesNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

ThyrotropinPituitary Hormones, AnteriorPituitary HormonesPeptide HormonesHormonesHormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

  • Joanna Klubo-Gwiezdzinska, M.D.

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

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Padmasree Veeraraghavan, R.N.

CONTACT

Joanna Klubo-Gwiezdzinska, M.D.

CONTACT

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 13, 2019

First Posted

February 15, 2019

Study Start

July 29, 2019

Primary Completion (Estimated)

November 1, 2035

Study Completion (Estimated)

November 1, 2035

Last Updated

April 20, 2026

Record last verified: 2026-04-02

Data Sharing

IPD Sharing
Will not share

Subject level data will be shared upon request after appropriate collaboration agreements are in place.

Locations