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

This study is ongoing, but not recruiting participants.

Sponsor:

Collaborator:

Amgen

Information provided by (Responsible Party):

Bayer

ClinicalTrials.gov Identifier:

NCT00984282

First received: September 24, 2009

Last updated: January 13, 2017

Last verified: January 2017

History of Changes

Results First Received: August 19, 2013

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Thyroid Neoplasms
Interventions:	Drug: Sorafenib (Nexavar, BAY43-9006) Drug: Placebo

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of 556 enrolled participants, 137 failed screening, 209 were randomized to receive sorafenib, 210 were randomized to placebo. One participant was never treated (placebo) and 2 were randomized by mistake (sorafenib) then re-randomized with different subject numbers. Therefore, 207 participants received sorafenib and 209 received placebo.

Reporting Groups

	Description
DB Sorafenib First, Then Option of OL Sorafenib Treatment	Double-blind period: Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (12 hours apart without food), 28 days comprise a cycle. Open-label (OL) period: Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (12 hours apart without food), 28 days comprise a cycle.
DB Placebo First, Then Option of OL Sorafenib Treatment	Double-blind period: participants received matching placebo tablets orally twice daily, 28 days comprised a cycle. Open-label (OL) period: participants on placebo who switched to sorafenib, received sorafenib 400 mg (2 x 200 mg) orally twice daily, 28 days comprise a cycle.

Participant Flow for 3 periods

Period 1: Double Blind Treatment

	DB Sorafenib First, Then Option of OL Sorafenib Treatment	DB Placebo First, Then Option of OL Sorafenib Treatment
STARTED	207	210
Received Treatment	207 ^[1]	209 ^[2]
COMPLETED	103	172
NOT COMPLETED	104	38
Adverse Event	38	6
Progression, recurrence or relapse	24	3
Physician Decision	1	2
Noncompliance with study medication	3	0
Progression by clinical judgment	1	0
Withdrawal by Subject	14	18
Lost to Follow-up	3	0
Death	8	4
Not treated	0	1
Switched to follow-up	12	4

^[1]	Subjects at Risk/Safety Population - in RG1 (RG= Reporting Group for Safety Data)
^[2]	Subjects at Risk/Safety Population - in RG2 (RG= Reporting Group for Safety Data)

Period 2: Open-label Treatment

	DB Sorafenib First, Then Option of OL Sorafenib Treatment	DB Placebo First, Then Option of OL Sorafenib Treatment
STARTED	86	161
Received Treatment	86 ^[1]	161 ^[2]
COMPLETED	0	0
NOT COMPLETED	86	161
Adverse Event	17	29
Withdrawal by Subject	6	21
Death	5	15
Progression, recurrence or relapse	37	77
Lost to Follow-up	1	0
Ongoing with treatment	19	18
Non-compliant with study medication	1	0
Target lesion removed	0	1

^[1]	Subjects at Risk/Safety Population - in RG3 (RG= Reporting Group for Safety Data)
^[2]	Subjects at Risk/Safety Population - in RG4 (RG= Reporting Group for Safety Data)

Period 3: Long Term Follow-up

	DB Sorafenib First, Then Option of OL Sorafenib Treatment	DB Placebo First, Then Option of OL Sorafenib Treatment
STARTED	114 ^[1]	117 ^[1]
COMPLETED	0	0
NOT COMPLETED	114	117
Withdrawal by Subject	18	15
Death	55	72
Lost to Follow-up	8	4
Ongoing with treatment	33	26

^[1]	Participants entered long-term follow-up if terminated double-blind or open-label periods

Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
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.
Placebo	Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle.
Total	Total of all reporting groups

Baseline Measures

Sorafenib (Nexavar, BAY43-9006)

Placebo

Total

Overall Participants Analyzed
[Units: Participants]

207

210

417

Age
[Units: Years]
Mean (Standard Deviation)

61.5 (11.2)

62.0 (11.7)

61.8 (11.4)

Age, Customized
[Units: Participants]

< 60 years

161

>= 60 years

127

129

256

Gender
[Units: Participants]
Count of Participants

Female

103 49.8%

115 54.8%

218 52.3%

Male

104 50.2%

95 45.2%

199 47.7%

Geographic region
[Units: Participants]

Europe

124

125

249

North America

Asia

ECOG (Eastern Cooperative Oncology Group) performance status ^[1]
[Units: Participants]

Missing

130

129

259

143

^[1]	The ECOG PS required for the study was 0 (fully active), 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature), or 2 (ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours)

Site of target/nontarget lesions at baseline - organ class ^[1]
[Units: Participants]

Lung

178

181

359

Lymph node

113

101

214

Bone

113

^[1]	Participants could have had more than one site.

Outcome Measures

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1. Primary:

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 ]

Measure Type	Primary
Measure Title	Progression-free Survival (PFS) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation
Measure Description	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.
Time Frame	Final analysis to be performed when approximately 267 progression-free survival events (centrally assessed) had occurred, study duration approximately three years

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set (FAS). The primary population for efficacy analysis was the FAS. The FAS was identical to the intent-to-treat (ITT) population, which was defined as all randomized participants. Participants were analyzed as randomized.

Reporting Groups

	Description
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
Placebo	Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle

Measured Values

	Sorafenib (Nexavar, BAY43-9006)	Placebo
Participants Analyzed [Units: Participants]	207	210
Progression-free Survival (PFS) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation [Units: Days] Median (95% Confidence Interval)	329 (278 to 393)	175 (160 to 238)

Statistical Analysis 1 for Progression-free Survival (PFS) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation

Groups ^[1]	All groups
Statistical Test Type ^[2]	Superiority or Other
Statistical Method ^[3]	Log Rank
P Value ^[4]	<0.0001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The two treatment groups were compared using a stratified one-sided log rank test with an overall alpha of 0.01 stratified by age group and region. The null hypothesis that both treatment arms have the same PFS distribution will be tested against the alternative hypothesis that the distribution of PFS times in the sorafenib arm is different from the control arm according to the Lehmann alternative, which is equivalent to the assumption of proportional hazards of the treatment arms.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	No text entered.
[3]	Other relevant method information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	stratified by age group (< 60 years, >= 60 years) and region (Europe, North-America, Asia)

Statistical Analysis 2 for Progression-free Survival (PFS) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation

Groups ^[1]	All groups
Statistical Test Type ^[2]	Superiority or Other
Statistical Method ^[3]	Regression, Cox
Hazard Ratio (HR) ^[4]	0.587
95% Confidence Interval	0.454 to 0.758

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	No text entered.
[3]	Other relevant method information, such as adjustments or degrees of freedom:
	stratified by age group and region
[4]	Other relevant estimation information:
	No text entered.

2. Secondary:

Overall Survival (OS) [ Time Frame: From randomization of the first subject until the database cut-off (14 Jul 2015), study duration approximately six years ]

Measure Type	Secondary
Measure Title	Overall Survival (OS)
Measure Description	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 Frame	From randomization of the first subject until the database cut-off (14 Jul 2015), study duration approximately six years

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set (FAS)

Reporting Groups

	Description
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
Placebo	Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle

Measured Values

	Sorafenib (Nexavar, BAY43-9006)	Placebo
Participants Analyzed [Units: Participants]	207	210
Overall Survival (OS) [Units: Percentage of participants]	49.8	51.9

Statistical Analysis 1 for Overall Survival (OS)

Groups ^[1]	All groups
Statistical Test Type ^[2]	Superiority or Other
Statistical Method ^[3]	Log Rank
P Value ^[4]	0.2847

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	No text entered.
[3]	Other relevant method information, such as adjustments or degrees of freedom:
	stratified by age group and region
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 2 for Overall Survival (OS)

Groups ^[1]	All groups
Statistical Test Type ^[2]	Superiority or Other
Statistical Method ^[3]	Regression, Cox
Hazard Ratio (HR) ^[4]	0.924
95% Confidence Interval	0.705 to 1.212

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	No text entered.
[3]	Other relevant method information, such as adjustments or degrees of freedom:
	stratified by age group and region
[4]	Other relevant estimation information:
	No text entered.

3. Secondary:

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 ]

Measure Type	Secondary
Measure Title	Time to Progression (TTP) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation
Measure Description	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])
Time Frame	From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS

Reporting Groups

	Description
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
Placebo	Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle

Measured Values

	Sorafenib (Nexavar, BAY43-9006)	Placebo
Participants Analyzed [Units: Participants]	207	210
Time to Progression (TTP) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation [Units: Days] Median (95% Confidence Interval)	337 (283 to 451)	175 (160 to 238)

Statistical Analysis 1 for Time to Progression (TTP) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation

Groups ^[1]	All groups
Statistical Test Type ^[2]	Superiority or Other
Statistical Method ^[3]	Log Rank
P Value ^[4]	<0.0001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	No text entered.
[3]	Other relevant method information, such as adjustments or degrees of freedom:
	stratified by age group and region
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 2 for Time to Progression (TTP) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation

Groups ^[1]	All groups
Statistical Test Type ^[2]	Superiority or Other
Statistical Method ^[3]	Regression, Cox
Hazard Ratio (HR) ^[4]	0.557
95% Confidence Interval	0.429 to 0.724

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	No text entered.
[3]	Other relevant method information, such as adjustments or degrees of freedom:
	stratified by age group and region
[4]	Other relevant estimation information:
	No text entered.

4. Secondary:

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 ]

Measure Type	Secondary
Measure Title	Disease Control Rate (DCR) Based on Central Assessment
Measure Description	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.
Time Frame	From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per protocol set (PPS). A participant was included in the PPS if he/she was randomized and was evaluable for tumor response based on imaging data, had exposure to study medication, and had no major protocol deviations.

Reporting Groups

	Description
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
Placebo	Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle

Measured Values

	Sorafenib (Nexavar, BAY43-9006)	Placebo
Participants Analyzed [Units: Participants]	196	201
Disease Control Rate (DCR) Based on Central Assessment [Units: Percentage of participants] Number (95% Confidence Interval)	86.2 (80.6 to 90.7)	74.6 (68.0 to 80.5)

Statistical Analysis 1 for Disease Control Rate (DCR) Based on Central Assessment

Groups ^[1]	All groups
Statistical Test Type ^[2]	Superiority or Other
Statistical Method ^[3]	Cochran-Mantel-Haenszel
P Value ^[4]	0.0015
Difference of response rates ^[5]	11.7
95% Confidence Interval	3.9 to 19.4

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	No text entered.
[3]	Other relevant method information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	stratified by age group and region
[5]	Other relevant estimation information:
	Difference of disease control rates sorafenib minus placebo. Cochran-Mantel-Haenszel confidence interval stratified by age group and region

5. Secondary:

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 ]

Measure Type	Secondary
Measure Title	Response Rate Based on Central Assessment
Measure Description	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.
Time Frame	From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PPS

Reporting Groups

	Description
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
Placebo	Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle

Measured Values

	Sorafenib (Nexavar, BAY43-9006)	Placebo
Participants Analyzed [Units: Participants]	196	201
Response Rate Based on Central Assessment [Units: Percentage of participants] Number (95% Confidence Interval)	12.24 (8.01 to 17.67)	0.5 (0.01 to 2.74)

Statistical Analysis 1 for Response Rate Based on Central Assessment

Groups ^[1]	All groups
Statistical Test Type ^[2]	Superiority or Other
Statistical Method ^[3]	Cochran-Mantel-Haenszel
P Value ^[4]	<0.0001
Difference in response rate ^[5]	11.8
95% Confidence Interval	7.0 to 16.5

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	No text entered.
[3]	Other relevant method information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	stratified by age group and region
[5]	Other relevant estimation information:
	Difference of response rates sorafenib minus placebo. Cochran-Mantel-Haenszel confidence interval stratified by age group and region

6. Secondary:

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 ]

Measure Type	Secondary
Measure Title	Duration of Response (DOR) Based on Central Assessment
Measure Description	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.
Time Frame	From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS - responders only

Reporting Groups

	Description
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
Placebo	Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle

Measured Values

	Sorafenib (Nexavar, BAY43-9006)	Placebo
Participants Analyzed [Units: Participants]	24	1
Duration of Response (DOR) Based on Central Assessment [Units: Days] Median (Full Range)	309 (226 to 505)	NA ^[1]

[1]	only one subject with PR

No statistical analysis provided for Duration of Response (DOR) Based on Central Assessment

7. Secondary:

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 ]

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

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PPS

Reporting Groups

	Description
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
Placebo	Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle

Measured Values

	Sorafenib (Nexavar, BAY43-9006)	Placebo
Participants Analyzed [Units: Participants]	196	201
Maximum Percent Reduction in Target Lesion Size Based on Central Assessment [Units: Percentage of participants]
Reduction ≥ 30%	17.3	1.0
Reduction ≥ 20% but < 30%	15.3	1.5
Reduction ≥ 10% but < 20%	22.4	3.5
Reduction > 0% but < 10%	22.4	21.9
Growth ≥ 0%	12.8	62.7
Not assessed	9.7	9.5

No statistical analysis provided for Maximum Percent Reduction in Target Lesion Size Based on Central Assessment

8. Secondary:

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) ]

Measure Type	Secondary
Measure Title	AUC(0-12h),ss (Area Under the Concentration Time Curve From Time 0 to 12 Hours at Steady State)
Measure Description	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.
Time Frame	A single pharmacokinetic plasma sample was collected at steady state (after 14 days of uninterrupted, unmodified sorafenib dosing)

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic (PK) analysis set=participants with PK data collected after 14 days of uninterrupted and unmodified dosing of sorafenib. If an interruption occurred within 14 days prior to the sample, no doses may be missed for 3 days prior to the sample, and no more than 3 doses could be missed 4 to 14 days prior to the sample collection date.

Reporting Groups

	Description
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

Measured Values

	Sorafenib (Nexavar, BAY43-9006)
Participants Analyzed [Units: Participants]	113
AUC(0-12h),ss (Area Under the Concentration Time Curve From Time 0 to 12 Hours at Steady State) [Units: mg*h/L] Geometric Mean (Standard Deviation)	75.4 (1.5)

No statistical analysis provided for AUC(0-12h),ss (Area Under the Concentration Time Curve From Time 0 to 12 Hours at Steady State)

Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The investigator must discuss any publication with the sponsor prior to release and obtain written consent of the sponsor on the intended publication. He/she must send a draft manuscript of the publication 30 days in advance of submission in order to obtain approval prior to submission of the final version for publication. In case of a difference of opinion, the contents will be discussed in order to find a solution which satisfies both parties.

Results Point of Contact:

Name/Title: Therapeutic Area Head
Organization: BAYER
e-mail: clinical-trials-contact@bayerhealthcare.com

Publications of Results:

Worden F, Fassnacht M, Shi Y, Hadjieva T, Bonichon F, Gao M, Fugazzola L, Ando Y, Hasegawa Y, Park DJ, Shong YK, Smit JW, Chung J, Kappeler C, Meinhardt G, Schlumberger M, Brose MS. Safety and tolerability of sorafenib in patients with radioiodine-refractory thyroid cancer. Endocr Relat Cancer. 2015 Dec;22(6):877-87. doi: 10.1530/ERC-15-0252.

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

Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, Bastholt L, de la Fouchardiere C, Pacini F, Paschke R, Shong YK, Sherman SI, Smit JW, Chung J, Kappeler C, Peña C, Molnár I, Schlumberger MJ; DECISION investigators. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. 2014 Jul 26;384(9940):319-28. doi: 10.1016/S0140-6736(14)60421-9. Epub 2014 Apr 24.

Brose MS, Nutting CM, Sherman SI, Shong YK, Smit JW, Reike G, Chung J, Kalmus J, Kappeler C, Schlumberger M. Rationale and design of decision: a double-blind, randomized, placebo-controlled phase III trial evaluating the efficacy and safety of sorafenib in patients with locally advanced or metastatic radioactive iodine (RAI)-refractory, differentiated thyroid cancer. BMC Cancer. 2011 Aug 11;11:349. doi: 10.1186/1471-2407-11-349.

Responsible Party:	Bayer
ClinicalTrials.gov Identifier:	NCT00984282 History of Changes
Other Study ID Numbers:	14295 2009-012007-25 ( EudraCT Number )
Study First Received:	September 24, 2009
Results First Received:	August 19, 2013
Last Updated:	January 13, 2017

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