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

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.

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Study Overview

• Status: Recruiting
• Conditions: Thyroid Cancer
• Intervention / Treatment: Drug: Thyrogen; Radiation: I-131; Radiation: I-124; Other: Thyroid hormone withdrawal

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Padmasree Veeraraghavan, N.P.; Phone Number: (301) 451-7710; Email: padmasree.veeraraghavan@nih.gov
• Study Contact Backup: Name: Joanna Klubo-Gwiezdzinska, M.D.; Phone Number: (301) 496-5052; Email: joanna.klubo-gwiezdzinska@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY8664111010 800-411-1222; Email: prpl@cc.nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITERIA:

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

  • underwent total thyroidectomy +/- 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 -na(SqrRoot) ve 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 124I PET/CT scan after rhTSH; 124I PET/CT scan after preparation with human recombinant TSH	Drug: Thyrogen; intramuscular injection administered once/day for 2 consecutive days at Week 3; then once annually for subjects who meet criteria.; Radiation: 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; Radiation: I-124; one capsule ingested orally once at Week 3, and Week 8; then administered once annually to subjects who meet criteria.
Active Comparator: 124I PET/CT scan after thyroid hormone withdrawal; 124I PET/CT scan after preparation with thyroid hormone withdrawal	Radiation: 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; Radiation: I-124; one capsule ingested orally once at Week 3, and Week 8; then administered once annually to subjects who meet criteria.; Other: Thyroid hormone withdrawal; withdrawal of thyroid hormone during weeks 4 through 8

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Joanna Klubo-Gwiezdzinska, M.D., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2019
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: February 13, 2019
• First Submitted That Met QC Criteria: February 14, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 15, 2024

More Information

Terms related to this study

• Keywords: PET/CT; Metastases; Thyroid Cancer; 124-I; Radioiodine
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: 190050; 19-DK-0050

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: .Subject level data will be shared upon request after appropriate collaboration agreements are in place.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No