We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Nexavar® Versus Placebo in Locally Advanced/Metastatic RAI-Refractory Differentiated Thyroid Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00984282
Recruitment Status : Completed
First Posted : September 25, 2009
Results First Posted : December 10, 2013
Last Update Posted : September 13, 2018
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Bayer

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
Trial of sorafenib versus placebo in the treatment of locally advanced or metastatic differentiated thyroid cancer refractory to radioiodine

Condition or disease Intervention/treatment Phase
Thyroid Neoplasms Drug: Sorafenib (Nexavar, BAY43-9006) Drug: Placebo Phase 3

Detailed Description:
Eligible subjects were randomized 1:1 to sorafenib 800 mg daily or matching placebo. Progression was assessed every 8 weeks by modified RECIST criteria. Subjects had the option to unblind study treatment after progression and to receive open label sorafenib regardless of initial treatment assignment. Following discontinuation of study treatment, subjects were followed for survival every 3 months in long-term follow-up. Subjects who terminated study treatment (either double only or double blind and open label) for reasons other than death, lost to follow-up or consent withdrawn entered long-term follow up
Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 417 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind Randomized Phase III Study Evaluating the Efficacy and Safety of Sorafenib Compared to Placebo in Locally Advanced/Metastatic RAI-Refractory Differentiated Thyroid Cancer
Actual Study Start Date : October 15, 2009
Actual Primary Completion Date : August 31, 2012
Actual Study Completion Date : August 30, 2017

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Sorafenib (Nexavar, BAY43-9006)
Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (12 hours apart without food), 28 days comprise a cycle
 Drug: Sorafenib (Nexavar, BAY43-9006)
Sorafenib 400 mg will be administered orally, twice daily (approximately every 12 hours).
Placebo Comparator: Placebo
Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle
 Drug: Placebo
Placebo (2 tablets) will be administered orally, twice daily (approximately every 12 hours).


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Progression-free Survival (PFS) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation [ Time Frame: Final analysis to be performed when approximately 267 progression-free survival events (centrally assessed) had occurred, study duration approximately three years ]
    PFS=time from randomization to first observed disease progression (radiological according to central assessment or clinical due to bone irradiation, whichever is earlier), or death due to any cause, if death occurred before progression. Progression was assessed by RECIST criteria, version 1.0, modified for bone lesions. PFS for participants without disease progression or death at the time of analysis or unblinding were censored at the last date of tumor assessment before unblinding. Participants with no tumor evaluation after baseline were censored at Day 1. PD (Progression Disease)=At least a 20% increase in sum of longest diameters (LD) of measured lesions taking as reference the smallest sum LD on study since the treatment started or the appearance of 1 or more new lesions. New lesions also constituted PD. In exceptional circumstances, unequivocal progression of a nonmeasured lesion may have been accepted as evidence of disease progression in participants with measurable disease.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: From randomization of the first subject until the database cut-off (30 AUG 2017), study duration approximately eight years ]
    Overall survival was defined as the time (days) from date of randomization to date of death due to any cause. Subjects still alive at the time of analysis were censored at their date of last contact. Since the median value could not be estimated due to censored data, the percentage of participants who died is presented.

  2. Time to Progression (TTP) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation [ Time Frame: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years ]
    Time to progression was defined at the time (days) from randomization to progression (based on central assessment [radiological and clinical progression due to bone irradiation])

  3. Disease Control Rate (DCR) Based on Central Assessment [ Time Frame: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years ]
    Disease control rate was defined as the proportion of subjects whose best response was complete response (CR), partial response (PR), or stable disease (SD). Per Response Evaluation Criteria in Solid Tumors (RECIST) criteria, CR and PR were to be confirmed by another scan at least 4 weeks later; SD had to be documented at least 4 weeks after date of randomization. CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). PR = At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum. SD = steady state of disease which is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

  4. Response Rate Based on Central Assessment [ Time Frame: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years ]
    Response rate was defined as the proportion of subjects whose best response was CR or PR. Per RECIST, CR and PR was to be confirmed by another scan at least 4 weeks later. CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). PR = At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum.

  5. Duration of Response (DOR) Based on Central Assessment [ Time Frame: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years ]
    Duration of response was defined as the time from the first documented objective response of PR or CR, whichever was noted earlier, to disease progression or death (if death occurred before progression was documented). CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). PR = At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum.

  6. Maximum Percent Reduction in Target Lesion Size Based on Central Assessment [ Time Frame: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years ]
    The magnitude of change from baseline in target lesion size in evaluable participants with scans was determined.

  7. AUC(0-12h),ss (Area Under the Concentration Time Curve From Time 0 to 12 Hours at Steady State) [ Time Frame: A single pharmacokinetic plasma sample was collected at steady state (after 14 days of uninterrupted, unmodified sorafenib dosing) ]
    Sorafenib AUC(0-12h),ss (area under the concentration time curve from time 0 to 12 hours at steady state) was estimated from the steady state plasma concentration.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Locally advanced or metastatic differentiated thyroid cancer (papillary, follicular and Hurthle cell)
  • Poorly differentiated and other thyroid variants (e.g. insular, tall cell, etc.) are eligible provided that the histology has no medullary differentiation nor anaplastic features
  • Progression within 14 months (RECIST [Response Evaluation Criteria in Solid Tumors] should be used as a basis for the assessment of disease progression)
  • RAI (radioactive iodine) refractory

Exclusion Criteria:

  • Histologic subtypes of thyroid cancer other than differentiated (i.e. like anaplastic and medullary carcinoma, lymphoma or sarcoma)
  • Prior anti-cancer treatment with tyrosine kinase inhibitors, monoclonal antibodies (licensed or investigational) that target VEGF (vascular endothelial growth factor) or VEGF Receptors or other targeted agents
  • Prior anti-cancer treatment for thyroid cancer with use of chemotherapy (low dose chemotherapy for radiosensitization is allowed) or Thalidomide or any of its derivatives
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00984282


Locations
Show Show 81 study locations
Sponsors and Collaborators
Bayer
Amgen
Investigators
Layout table for investigator information
Study Director: Bayer Study Director Bayer
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00984282    
Other Study ID Numbers: 14295
2009-012007-25 ( EudraCT Number )
First Posted: September 25, 2009    Key Record Dates
Results First Posted: December 10, 2013
Last Update Posted: September 13, 2018
Last Verified: August 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bayer:
RAI-Refractory
Differentiated
Follicular
Papillary
Hurthle
Additional relevant MeSH terms:
Layout table for MeSH terms
Thyroid Neoplasms
Thyroid Diseases
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
 Head and Neck Neoplasms
Sorafenib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action