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

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

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.

Study Overview

• Status: Completed
• Conditions: Thyroid Neoplasms
• Intervention / Treatment: Drug: Sorafenib (Nexavar, BAY43-9006); Drug: Other Multikinase inhibitors

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 667

Contacts and Locations

Study Locations

• Algeria
  • Multiple Locations, Algeria
• Argentina
  • Multiple Locations, Argentina
• Brazil
  • Multiple Locations, Brazil
• Egypt
  • Multiple Locations, Egypt
• France
  • Multiple Locations, France
• Germany
  • Multiple Locations, Germany
• Greece
  • Multiple Locations, Greece
• India
  • Multiple Locations, India
• Japan
  • Multiple Locations, Japan
• Lebanon
  • Multiple Locations, Lebanon
• Mexico
  • Multiple Locations, Mexico
• Netherlands
  • Multiple Locations, Netherlands
• Philippines
  • Multiple Locations, Philippines
• Russian Federation
  • Multiple Locations, Russian Federation
• Saudi Arabia
  • Multiple Locations, Saudi Arabia
• Spain
  • Multiple Locations, Spain
• Taiwan
  • Multiple Locations, Taiwan
• Turkey
  • Multiple Locations, Turkey
• United States
  • Alabama
    • Birmingham, Alabama, United States
  • California
    • Los Angeles, California, United States
    • Torrance, California, United States
  • Colorado
    • Aurora, Colorado, United States
  • District of Columbia
    • Washington, District of Columbia, United States
  • Florida
    • Plantation, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
  • Hawaii
    • Honolulu, Hawaii, United States
  • Illinois
    • Chicago, Illinois, United States
  • Louisiana
    • New Orleans, Louisiana, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • Michigan
    • Ann Arbor, Michigan, United States
  • New York
    • Bronx, New York, United States
  • North Carolina
    • Durham, North Carolina, United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
  • Texas
    • Dallas, Texas, United States

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Any setting that provides treatment for progressive asymptomatic RAI refractory DTC

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MKI patients; 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); Patients can get sorafenib at any time during study.; Drug: Other Multikinase inhibitors; Patients can get MKIs at any time during study.
non-MKI patients; 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); Patients can get sorafenib at any time during study.; Drug: Other Multikinase inhibitors; Patients can get MKIs at any time during study.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bayer
• Investigators: Study Director: Bayer Study Director, Bayer

Publications and helpful links

General Publications

• Brose MS, Smit JWA, Lin CC, Tori M, Bowles DW, Worden F, Shen DH, Huang SM, Tsai HJ, Alevizaki M, Peeters RP, Takahashi S, Rumyantsev P, Guan R, Babajanyan S, Ozgurdal K, Sugitani I, Pitoia F, Lamartina L. Multikinase Inhibitors for the Treatment of Asymptomatic Radioactive Iodine-Refractory Differentiated Thyroid Cancer: Global Noninterventional Study (RIFTOS MKI). Thyroid. 2022 Sep;32(9):1059-1068. doi: 10.1089/thy.2022.0061.
• Porcelli T, Luongo C, Sessa F, Klain M, Masone S, Troncone G, Bellevicine C, Schlumberger M, Salvatore D. Long-term management of lenvatinib-treated thyroid cancer patients: a real-life experience at a single institution. Endocrine. 2021 Aug;73(2):358-366. doi: 10.1007/s12020-021-02634-z. Epub 2021 Feb 3.
• Brose MS, Smit J, Lin CC, Pitoia F, Fellous M, DeSanctis Y, Schlumberger M, Tori M, Sugitani I. Timing of multikinase inhibitor initiation in differentiated thyroid cancer. Endocr Relat Cancer. 2017 May;24(5):237-242. doi: 10.1530/ERC-17-0016. Epub 2017 Mar 7.

Helpful Links

• Click here to find results for studies related to Bayer Healthcare products.

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2015
• Primary Completion (Actual): June 10, 2020
• Study Completion (Actual): July 24, 2020

Study Registration Dates

• First Submitted: November 25, 2014
• First Submitted That Met QC Criteria: November 28, 2014
• First Posted (Estimated): December 1, 2014

Study Record Updates

• Last Update Posted (Actual): June 8, 2023
• Last Update Submitted That Met QC Criteria: June 7, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Progressive radioactive iodine refractory differentiated thyroid carcinoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: 17852; NX1401 (Other Identifier: Company internal)

Drug and device information, study documents

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