An Observational Study in Differentiated Thyroid Cancer Which is Radioactive Iodine (RAI) Refractory to Assess the Use of Multikinase Inhibitors

Study Overview
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Brief Summary
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The purpose of the study was to assess the use of Multikinase Inhibitors (MKIs) in the treatment of patients with a progressive differentiated thyroid carcinoma (DTC) refractory to radioactive iodine (RAI) who do not have any symptoms.

Detailed Description
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The primary objective of this study was to compare time to symptomatic progression (TTSP) from study entry in asymptomatic patients with RAI-refractory progressive DTC for whom there is a decision to initiate MKIs at study entry with that of asymptomatic patients with RAI-refractory progressive DTC for whom there is a decision to not initiate MKIs at study entry.

Official Title
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RIFTOS MKI - Radioactive Iodine reFractory Asymptomatic Patients in Differentiated Thyroid Cancer - an Observational Study to Assess the Use of Multikinase Inhibitors

Conditions
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Thyroid Neoplasms

Intervention / Treatment
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* Drug: Sorafenib (Nexavar, BAY43-9006)
* Drug: Other Multikinase inhibitors


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically/cytologically documented DTC (papillary, follicular, Hurthle cell, and poorly differentiated carcinoma) DTC refractory to RAI Radiological progression and preferably according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 No symptoms due to DTC >/=1cm diameter of lesion confirmed by radiological exam Life expectancy of at least 6 months Exclusion Criteria: Plan to be treated according to a clinical trial protocol for intervention including a locoregional therapy or systemic therapy Previous treatment with MKIs for advanced disease Hospice patients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MKI patients<br>Asymptomatic patients with RAI-refractory progressive DTC for whom there is a decision to initiate MKIs at study entry. For patients on sorafenib, treatment start and stop dates will be collected along with any adverse events observed. | Drug: Sorafenib (Nexavar, BAY43-9006)<br>* Patients can get sorafenib at any time during study.<br>Drug: Other Multikinase inhibitors<br>* Patients can get MKIs at any time during study.<br>|
| non-MKI patients<br>Asymptomatic patients with RAI-refractory progressive DTC for whom there is a decision to not initiate MKIs at study entry. For patients on sorafenib, treatment start and stop dates will be collected along with any adverse events observed. | Drug: Sorafenib (Nexavar, BAY43-9006)<br>* Patients can get sorafenib at any time during study.<br>Drug: Other Multikinase inhibitors<br>* Patients can get MKIs at any time during study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to symptomatic progression (TTSP) from study entry | TTSP is defined as the time interval from the day of study entry to the date of first symptomatic progression. Patients who do not have a symptomatic progression at the time of analysis will be censored at the date of their last evaluable assessment. | Up to 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) from time of study entry | Defined as the time interval from the date of study entry to death due to any cause. Patients alive at the time of analysis will be censored at the last date known to be alive. | Up to 6 years | 
| Progression free survival (PFS) from time of study entry | Defined as the time interval from the date of study entry to date of first progression or death due to any cause, whichever comes first. The actual date of tumor assessments will be used for this calculation. Patients without a progression or death will be censored at their last evaluable date of tumor evaluation. | Up to 6 years | 
| OS from time of being diagnosed as radioactive iodine (RAI) refractory | Defined as the time interval from the day of being diagnosed as RAI refractory to death due to any cause. Patients alive at the time of analysis will be censored at the last date known to be alive. | Up to 6 years | 
| Post-progression survival (PPS) from time of symptomatic progression | Defined as the time interval from the date of symptomatic progression to death due to any cause. Patients without symptomatic progression will be excluded from analysis and patients who are alive at the time of analysis will be censored at the last date when they were known to be alive. | Up to 6 years | 
| OS from initiation of the first Multikinase Inhibitor (MKI) | Defined as the time interval from the day of start of the first MKI to death due to any cause. Patients alive at the time of analysis will be censored at the last date when they were known to be alive. | Up to 6 years | 
| PFS from initiation of first MKI | Defined as the time interval from the day of start of first MKI to date of first progression or death due to any cause, whichever comes first. The actual date of tumor assessments will be used for this calculation. Patients without a progression or death will be censored at their last evaluable date of tumor evaluation. | Up to 6 years | 
| OS from initiation of any systemic treatment regimen | Defined as the time interval from the date of start of any systemic treatment regimen to death due to any cause. Patients alive at the time of analysis will be censored at the last date known to be alive. | Up to 6 years | 
| PFS from initiation of any systemic treatment regimen | Defined as the time interval from the date of start of any systemic treatment regimen to date of first progression or death due to any cause, whichever comes first. Patients without a progression or death will be censored at their last evaluable date of tumor evaluation. | Up to 6 years | 
| Duration of each systemic treatment regimen | Defined as the time interval from the day of start of a treatment to the date of permanent discontinuation of a treatment (regardless of the reason for discontinuation including death). It includes interruption or drug holiday. | Up to 6 years | 
| Response assessment to each systemic treatment regimen according to the categories Complete Response, Partial Response, Stable Disease, Clinical Progression, Radiological Progression, and Not evaluable at this visit | In case of Clinical Progression the CRF will ask for the presence of specific symptoms. | Up to 6 years | 
| OS from initiation of sorafenib | Defined as the time interval from the day of start of sorafenib to death due to any cause. Patients alive at the time of analysis will be censored at the last date known to be alive. | Up to 6 years | 
| PFS from initiation of sorafenib | Defined as the time interval from the date of start of sorafenib to date of first progression or death due to any cause, whichever comes first. Patients without a progression or death will be censored at their last evaluable date of tumor evaluation. | Up to 6 years | 
| Daily dose of sorafenib per patient throughout the treatment period |  | Up to 6 years | 
| Number of adverse events during treatment with sorafenib |  | Up to 6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Progressive radioactive iodine refractory differentiated thyroid carcinoma