The Use of 124-I-PET/CT Whole Body and Lesional Dosimetry in Differentiated Thyroid Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- 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)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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-
- •Pregnant or lactating women per self report.
- •Adults who are incapable of providing informed consent.
研究组 & 干预措施
124I PET/CT scan after rhTSH
124I PET/CT scan after preparation with human recombinant TSH
干预措施: I-124 (Radiation)
124I PET/CT scan after rhTSH
124I PET/CT scan after preparation with human recombinant TSH
干预措施: Thyrogen (Drug)
124I PET/CT scan after thyroid hormone withdrawal
124I PET/CT scan after preparation with thyroid hormone withdrawal
干预措施: Thyroid hormone withdrawal (Other)
124I PET/CT scan after thyroid hormone withdrawal
124I PET/CT scan after preparation with thyroid hormone withdrawal
干预措施: I-131 (Radiation)
124I PET/CT scan after thyroid hormone withdrawal
124I PET/CT scan after preparation with thyroid hormone withdrawal
干预措施: I-124 (Radiation)
124I PET/CT scan after rhTSH
124I PET/CT scan after preparation with human recombinant TSH
干预措施: I-131 (Radiation)
结局指标
主要结局
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)
时间窗: 9 weeks
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)
次要结局
未报告次要终点