Radioiodine-refractory thyroid cancer radioiodine-resistant thyroid cancer
Conditions
Interventions
I-124 dosimetry
Sponsors
Academisch Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria: • Age >= 18 years at the time of informed consent • Histologically or cytologically confirmed DTC (including papillary, follicular or Hürthle Cell carcinoma) • Progressive (biochemical or anatomic) disease for which lenvatinib is started as standard treatment at the discretion of the treating physician. • Measurable disease at baseline imaging (F-18 FDG PET) according to the definition of the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0 with at least one lesion >=1.0 cm in the longest diameter for a non-lymph node or >=1.5 cm in the short axis for a lymph node. • RAI-R disease on structural imaging, defined as any one of the following: o Metastatic lesions that are not RAI-avid on a diagnostic or intra-therapeutic RAI scan performed prior to enrolment in the current study o RAI-avid metastatic lesions which remained stable in size or progressed according to RECIST 1.1 criteria despite RAI treatment. Absence of response is observed during 6-9 months after high dose I-131 therapy. • No recent treatment for thyroid cancer: o No prior I-131 therapy is allowed =60%) • Life expectancy >=3 months • Ability to swallow and retain orally-administered medication and no clinically significant gastrointestinal abnormalities that may alter absorption • Creatinine =50 mL/min/1.73m2 or 24-hour urine creatinine clearance >=50 mL/min/1.73m2 • Adequate blood coagulation function as evidenced by an international normalized ratio (INR) =1.5 * 10^9/L o Hemoglobin >=9 g/dL (5.6 mmol/L) o Platelets >=100 *10^9/L • Adequate liver function with o Albumin >=25 g/L o Total bilirubin =1 year. • Sexually active women of childbearing potential must agree to use a highly effective method of contraception during the study and for at least 6 months after the last study treatment administration. Sexually active males patients must agree to use condom during the study and for at least 6 months after the last study treatment administration. Also, it is recommended their women of childbearing pot
Exclusion criteria
Exclusion criteria: • Concomitant or previous malignancies within the last 3 years. Patients are eligible for this study if they have been disease-free of the previous malignancy for at least 3 years, have a history of completely resected non-melanoma skin cancer and/or have indolent secondary malignancies. • Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression • Evidence of cardiovascular risk including any of the following: o Clinically relevant arrhythmias o Acute coronary syndromes, severe/unstable angina o Symptomatic congestive heart failure • Use of other investigational drugs within 28 days preceding the first dose of treatment in this study or during the study • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lenvatinib and/or to Thyrotropin alfa (human recombinant thyrotropin) or other known contents of the two drugs. • Inability to follow a low iodine diet or requiring medication with high content in iodide (e.g. amiodarone) • Patients who received iodinated intravenous contrast as part of a radiographic procedure within 6-8 weeks of study registration. Patients are eligible for this study if urinary iodine analysis reveals that the excess iodine has been adequately cleared after the last intravenous contrast administration • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements. • Pregnant, lactating or breast feeding women • Any medical or other condition that in the opinion of the investigator(s) would preclude the participation in a clinical study • Unwillingness or inability to comply with study and follow-up procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Fraction of RAI-R thyroid cancer patients who are eligible for I-131 therapy after 6- or 12-week lenvatinib treatment to an extent that clinically meaningful tumour radiation doses [Gy] can be safely delivered with acceptable I-131 activities [MBq] as determined by I-124 dosimetry of both lesions and healthy organs at risk. | — |
Secondary
| Measure | Time frame |
|---|---|
| • Extent of RAI uptake and retention at baseline and after 6- or 12-week lenvatinib • Optimal duration of lenvatinib treatment (6 weeks or 12 weeks) for maximum redifferentiation to occur. • Agreement between expected absorbed dose per lesion predicted by I-124 PET/CT dosimetry and actual absorbed dose per lesion determined by intra-therapeutic I-131 SPECT/CT dosimetry in patients in which I-131 therapy is warranted. • Metabolic and biochemical treatment response using F-18 FDG PET and unstimulated (TSH-suppressed) thyroglobulin levels, respectively. • Overall survival, best objective response and progression free survival. • Incidence and severity of toxicities according to CTCAE 5.0. • Quality of life An explorative endpoint of this study is to evaluate alterations at the transcriptional and translational level in biopted tumour lesions before and after lenvatinib treatment and to determine whether treatment response is related to genetical profiles. | — |
Countries
Netherlands
Outcome results
None listed