Participants will have been diagnosed with advanced progressive thyroid cancer and are about to start treatment with a tyrosine kinase inhibitor (TKI). The purpose of this study is to evaluate the efficacy and tolerability of tyrosine kinase inhibitor therapy (Lenvatinib or Sorafenib for differentiated thyroid cancer \[which includes papillary thyroid cancer, follicular thyroid cancer, and poorly differentiated thyroid cancer\]; and Cabozantinib or Vandetanib for medullary thyroid cancer) through adaptive (intermittent) versus conventional (continuous) regimen.
Population: Patients with advanced progressive 131I-refractory DTC or MTC will be enrolled to this study. Forty-five patients responding to TKI therapy (defined as 50% drop in tumor marker level within the first two months of treatment) will be randomized to receive TKI therapy either through adaptive (intermittent) or conventional (continuous) regimen.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
6
Standard of Care: Lenvatinib 24 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.
Standard of Care: Sorafenib 400 mg twice daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.
Standard of Care: Cabozantinib 140 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.
Standard of Care: Vandetanib 300 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States
Time to Tyrosine Kinase Inhibitor (TKI) Treatment Discontinuation Due to Progressive Disease
Median time-to-discontinuation (TTD) of treatment per study arm, due to Progressive Disease.
Time frame: 2 years
Time to Tyrosine Kinase Inhibitor (TKI) Treatment Discontinuation Due to Intolerability
Median time-to-discontinuation (TTD) of treatment per study arm, due to Intolerability.
Time frame: 2 years
Time to Tyrosine Kinase Inhibitor (TKI) Treatment Discontinuation Due to Disease Related Death
Median time-to-discontinuation (TTD) of treatment per study arm, due to Disease-related death at 2 years.
Time frame: 2 years
Overall Response Rate (ORR)
The response rate will be estimated using binomial theory with Wilson's method for the 95% confidence interval. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter (LD). Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started.
Time frame: Up to 48 months
Progression-free Survival (PFS)
The median progression-free survival rates will be estimated from the Kaplan-Meier curve with the 95% confidence interval obtained from Greenwood's formula. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: Up to 48 months
Overall Survival (OS)
The median overall survival rates will be estimated from the Kaplan-Meier curve with the 95% confidence interval obtained from Greenwood's formula.
Time frame: Up to 48 months
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