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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Onyx Pharmaceuticals
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00984282
First received: September 24, 2009
Last updated: May 8, 2014
Last verified: May 2014
  Purpose

Trial of sorafenib versus placebo in the treatment of locally advanced or metastatic differentiated thyroid cancer refractory to radioiodine


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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:
  • Overall Survival (OS) [ Time Frame: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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])

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    The magnitude of change from baseline in target lesion size in evaluable participants with scans was determined.

  • 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) ] [ Designated as safety issue: No ]
    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.


Enrollment: 417
Study Start Date: October 2009
Estimated Study Completion Date: June 2016
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00984282

  Show 98 Study Locations
Sponsors and Collaborators
Bayer
Onyx Pharmaceuticals
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided by Bayer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00984282     History of Changes
Other Study ID Numbers: 14295, 2009-012007-25
Study First Received: September 24, 2009
Results First Received: August 19, 2013
Last Updated: May 8, 2014
Health Authority: China: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Korea: Food and Drug Administration
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Saudi Arabia: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Sweden: Medical Products Agency
United States: Food and Drug Administration
Japan: Pharmaceuticals and Medical Devices Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Spain: Spanish Agency of Medicines
Austria: Agency for Health and Food Safety
Russia: Ministry of Health of the Russian Federation
Bulgaria: Bulgarian Drug Agency-BDA
Belgium: Federal Agency for Medicines and Healthcare Products- FAMHP
Denmark: The Danish Health and Medicines Authority-DHMA

Keywords provided by Bayer:
RAI-Refractory
Differentiated
Follicular
Papillary
Hurthle

Additional relevant MeSH terms:
Neoplasms
Thyroid Neoplasms
Thyroid Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Endocrine System Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 14, 2014