Study Of SU011248 Administered On A Continuous Daily Dosing Schedule In Patients With Gastrointestinal Stromal Tumor

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00137449
• Collaborator: (none)
• Enrollment: 60
• Locations: 4
• Arm: 1
• Duration (Months): 31
• Patients Per Site: 15
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

To evaluate the antitumor activity of SU011248 in advanced, imatinib mesylate-resistant gastrointestinal stromal tumor (GIST) when administered on a continuous daily dosing schedule

Condition or Disease	Intervention/Treatment	Phase
Gastrointestinal Stromal Tumors	Drug: SU011248	Phase 2

Detailed Description

Subjects experiencing clinical benefit after 1 year on study were offered continued treatment with SU011248 on a separate protocol.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Efficacy And Safety Study Of SU011248 Administered In A Continuous Daily Regimen In Patients With Advanced Gastrointestinal Stromal Tumor
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	Drug: SU011248; 37.5 mg once daily on a continuous daily dosing schedule. Study medication continued as long as patient was obtaining clinical benefit, or until significant toxicity, or withdrawal of consent, for up to 1 year on study.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Clinical Benefit Response (CBR) According to RECIST [Planned duration on this protocol of up to 1 year]

   CBR is defined as a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) for at least 24 weeks on study according to RECIST. Confirmed responses are those that persisted on repeat imaging >= 4 wks after initial response. Participants with no on-study radiographic tumor re-evaluation counted as non-responders.

Secondary Outcome Measures

1. Number of Participants by Best Confirmed Response Category According to RECIST [Planned duration on this protocol of up to 1 year]

   Best confirmed response (BCR) defined as best response [confirmed CR, confirmed PR, SD, PD(progressive disease), not evaluable (NE)] recorded from start of treatment until disease progression / recurrence. Best response of SD must have met SD criteria at least once after first dose at minimum interval of 6 weeks.

2. Number of Participants With Overall Confirmed Objective Disease Response (ORR) [Planned duration on this protocol of up to 1 year]

   Overall confirmed objective disease response is defined as a confirmed CR, or confirmed PR according to RECIST. Confirmed responses are those that persisted on repeat imaging >= 4 wks after initial response.

3. Duration of Stable Disease [Planned duration on this protocol of up to 1 year]

   Duration of SD is the time from the date of first documentation of stable disease to the date of first documentation of objective tumor progression or death due to any cause that occurred within 28 days after last dose of study medication, whichever occurred first.

4. Progression-free Survival (PFS) [Planned duration on this protocol of up to 1 year]

   PFS was defined as the time from the date of first dose of study medication to the date of first documentation of objective tumor progression or to death due to any cause that occurred on treatment including within 28 days after the last dose of study medication, whichever occurred first.

5. Time to Tumor Progression (TTP) [Planned duration on this protocol of up to 1 year]

   TTP was defined as the time from the date of first dose of study medication to the date of first documentation of objective tumor progression that occurred on treatment including within 28 days after the last dose of study medication.

6. Duration of Tumor Response (DR) [Descriptive Statistics] [Planned duration on this protocol of up to 1 year]

   DR was defined as the time from the date of first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the date of the first documentation of objective tumor progression or to death due to any cause that occurred within 28 days after the last dose of study medication, whichever occurred first.

7. Overall Survival (OS) and One-year Survival [Descriptive Statistics] [Survival status was collected by telephone contact every 2 months for up to 2 years from study entry.]

   Overall survival is defined as time from the date of first dose of study medication to the date of death due to any cause. One year survival rate defined as the probability that a patient is alive 1 year after the date of first study medication.

8. Score of FACIT-Fatigue Scale [Baseline, Day 1 & 15 of each treatment cycle]

   FACIT-Fatigue Scale: Overall score from 13-question questionnaire (measures fatigue/asthenia for patients with chronic, life-threatening illnesses). For each question, patient rates condition for the past week on a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). Maximum, minimum mean included data available for >=10 subjects.

9. Score of EQ-VAS (Euro Quality of Life -Visual Analog Scale) [Baseline, Day 1 &15 of each treatment cycle up to 1 year on study]

   EQ-VAS score on the self-rated "thermometer," indicating the patient's own assessment of their health status from 0 (worst) to 100 (best) imaginable health state. Change: median score at observation minus median score at baseline. Maximum changes (Increase or Decrease from baseline) included data available for >=10 subjects.

10. Score of EQ-5D (Euro Quality of Life-5 Dimension) Weighted Health Index [Baseline, Day 1 & 15 of each treatment cycle up to 1 year on study]

    EQ-5D: health status in 5 dimensions (mobility, self-care, pain/discomfort, anxiety/depression, usual activities) with a weighted health Index based on general population values where 0.0 = death and 1.0 = perfect health. Change: median index score at observation minus median index score at baseline (includes data available for >=10 subjects).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histopathologically proven diagnosis of malignant GIST that was not amenable to standard therapy.

• Failed prior treatment with imatinib mesylate, defined either by progression of disease (according to Response Evaluation Criterion in Solid Tumors (RECIST) or World Health Organization (WHO) criteria), or by significant toxicity during treatment with imatinib mesylate that precluded further treatment. Intolerance to prior imatinib mesylate therapy was defined as follows:

• Life-threatening adverse events (ie, Grade 4) at any dose (attempt to dose reduce or rechallenge not required) or Unacceptable toxicity induced by a moderate dose (eg, 400 mg/day), specifically, Grade 2 toxicity that was unacceptable to the patient (such as nausea) that persisted despite standard countermeasures

• Evidence of unidimensionally measurable disease.

Exclusion Criteria:

• Previous treatment on a SU011248 clinical trial.

• Diagnosis of any second malignancy within the last 3 years, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma, that had been adequately treated with no evidence of recurrent disease for 12 months.

• History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.

• Any of the following within the 12 months prior to starting the study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.

• Ongoing cardiac dysrhythmias of grade 2, atrial fibrillation of any grade, or QTc interval >450 msec for males or >470 msec for females.

• Hypertension that could not be controlled by medications (>150/100 mm/Hg despite optimal medical therapy).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Boston	Massachusetts	United States	02115
2	Pfizer Investigational Site	Lyon Cedex 08		France	69373
3	Pfizer Investigational Site	Villejuif		France	94805
4	Pfizer Investigational Site	Milano		Italy	20133

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00137449
• Other Study ID Numbers: A6181047
• First Posted: Aug 29, 2005
• Last Update Posted: Sep 15, 2009
• Last Verified: Sep 1, 2009

• Additional relevant MeSH terms: Gastrointestinal Stromal Tumors; Sunitinib

Study Results

Participant Flow

Pre-assignment Detail	Must have failed prior treatment with imatinib mesylate (IM) [defined as progression of disease using Response Evaluation Criteria in Solid Tumors(RECIST) or World Health Organization(WHO) criteria, or significant toxicity during treatment with IM precluding further treatment & Eastern Cooperative Oncology Group(ECOG) performance status of 0-1]

Arm/Group Title	AM Dose Sunitinib Malate	PM Dose Sunitinib Malate
Arm/Group Description	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.
Period Title: Overall Study
STARTED	30	30
COMPLETED	14	12
NOT COMPLETED	16	18

Baseline Characteristics

Arm/Group Title	AM Dose Sunitinib Malate	PM Dose Sunitinib Malate	Total
Arm/Group Description	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Total of all reporting groups
Overall Participants	30	30	60
Age (Count of Participants)
<=18 years	0 0%	0 0%	0.0 0%
Between 18 and 65 years	17 56.7%	18 60%	35.0 58.3%
>=65 years	13 43.3%	12 40%	25.0 41.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.3 (14.5)	57.0 (14.8)	58.2 (14.6)
Sex: Female, Male (Count of Participants)
Female	15 50%	17 56.7%	32.0 53.3%
Male	15 50%	13 43.3%	28.0 46.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Clinical Benefit Response (CBR) According to RECIST
Description	CBR is defined as a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) for at least 24 weeks on study according to RECIST. Confirmed responses are those that persisted on repeat imaging >= 4 wks after initial response. Participants with no on-study radiographic tumor re-evaluation counted as non-responders.
Time Frame	Planned duration on this protocol of up to 1 year

Outcome Measure Data

Analysis Population Description

ITT population (all subjects enrolled that received at least 1 dose of study medication) with measurable disease at baseline and correct histological cancer type. CR+PR+(SD for >=24 weeks)

Arm/Group Title	AM Dose Sunitinib Malate	PM Dose Sunitinib Malate	Total (Equals AM Plus PM Dose) Sunitinib Malate
Arm/Group Description	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.
Measure Participants	30	30	60
Number [participants]	15 50%	17 56.7%	32 53.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AM Dose Sunitinib Malate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	CBR Rate (percentage)
	Estimated Value	50.0
	Confidence Interval	() 95%; 31.3 to 68.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PM Dose Sunitinib Malate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	CBR Rate (percentage)
	Estimated Value	56.7
	Confidence Interval	() 95%; 37.4 to 74.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Total (Equals AM Plus PM Dose) Sunitinib Malate
	Comments	Null hypothesis that the true CBR <=20% vs the alternative hypothesis that the true clinical benefit rate is at least 35%. The sample size is determined using a single-stage design with an alpha level of 10% & 90% power. If >=17 CR, PR or SD for at least 24 weeks are observed, null hypothesis can be rejected with a 20% target false positive error rate. If <= 16 CR, PR,or SD for at least 24 weeks are observed, null hypothesis can not be rejected with a target false negative error rate of 10%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	CBR Rate (percentage)
	Estimated Value	53.3
	Confidence Interval	() 95%; 40.0 to 66.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants by Best Confirmed Response Category According to RECIST
Description	Best confirmed response (BCR) defined as best response [confirmed CR, confirmed PR, SD, PD(progressive disease), not evaluable (NE)] recorded from start of treatment until disease progression / recurrence. Best response of SD must have met SD criteria at least once after first dose at minimum interval of 6 weeks.
Time Frame	Planned duration on this protocol of up to 1 year

Outcome Measure Data

Analysis Population Description

ITT population (all subjects enrolled that received at least 1 dose of study medication) with measurable disease at baseline and correct histological cancer type.

Arm/Group Title	AM Dose Sunitinib Malate	PM Dose Sunitinib Malate	Total (Equals AM Plus PM Dose) Sunitinib Malate
Arm/Group Description	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.
Measure Participants	30	30	60
Complete Response (CR)	0 0%	0 0%	0 0%
Partial Response (PR)	3 10%	5 16.7%	8 13.3%
Stable Disease (SD)	20 66.7%	20 66.7%	40 66.7%
Progressive disease (PD)	2 6.7%	4 13.3%	6 10%
Not evaluable (NE)	5 16.7%	1 3.3%	6 10%

3. Secondary Outcome

Title	Number of Participants With Overall Confirmed Objective Disease Response (ORR)
Description	Overall confirmed objective disease response is defined as a confirmed CR, or confirmed PR according to RECIST. Confirmed responses are those that persisted on repeat imaging >= 4 wks after initial response.
Time Frame	Planned duration on this protocol of up to 1 year

Outcome Measure Data

Analysis Population Description

ITT population (all subjects enrolled that received at least 1 dose of study medication) with measurable disease at baseline and correct histological cancer type.

Arm/Group Title	AM Dose Sunitinib Malate	PM Dose Sunitinib Malate	Total (Equals AM Plus PM Dose) Sunitinib Malate
Arm/Group Description	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.
Measure Participants	30	30	60
Number [participants]	3 10%	5 16.7%	8 13.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AM Dose Sunitinib Malate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ORR rate (percentage)
	Estimated Value	10.0
	Confidence Interval	() 95%; 2.1 to 26.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	PR or CR responding tumor measurements confirmed by repeat studies performed at > 4 weeks after the criteria for response first met.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PM Dose Sunitinib Malate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ORR rate (percentage)
	Estimated Value	16.7
	Confidence Interval	() 95%; 5.6 to 34.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	PR or CR responding tumor measurements confirmed by repeat studies performed at > 4 weeks after the criteria for response first met.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Total (Equals AM Plus PM Dose) Sunitinib Malate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ORR rate (percentage)
	Estimated Value	13.3
	Confidence Interval	() 95%; 5.9 to 24.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	PR or CR responding tumor measurements confirmed by repeat studies performed at > 4 weeks after the criteria for response first met.

4. Secondary Outcome

Title	Duration of Stable Disease
Description	Duration of SD is the time from the date of first documentation of stable disease to the date of first documentation of objective tumor progression or death due to any cause that occurred within 28 days after last dose of study medication, whichever occurred first.
Time Frame	Planned duration on this protocol of up to 1 year

Outcome Measure Data

Analysis Population Description

ITT population (all subjects enrolled that received at least 1 dose of study medication) with measurable disease at baseline and correct histological cancer type.

Arm/Group Title	AM Dose Sunitinib Malate	PM Dose Sunitinib Malate	Total (Equals AM Plus PM Dose) Sunitinib Malate
Arm/Group Description	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.
Measure Participants	30	30	60
>= 12 weeks	19 63.3%	14 46.7%	33 55%
>= 24 weeks	12 40%	12 40%	24 40%

5. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	PFS was defined as the time from the date of first dose of study medication to the date of first documentation of objective tumor progression or to death due to any cause that occurred on treatment including within 28 days after the last dose of study medication, whichever occurred first.
Time Frame	Planned duration on this protocol of up to 1 year

Outcome Measure Data

Analysis Population Description

ITT population (all subjects enrolled that received at least 1 dose of study medication) with measurable disease at baseline and correct histological cancer type.

Arm/Group Title	AM Dose Sunitinib Malate	PM Dose Sunitinib Malate	Total (Equals AM Plus PM Dose) Sunitinib Malate
Arm/Group Description	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.
Measure Participants	30	30	60
Patient was censored	12 40%	10 33.3%	22 36.7%
Patient observed to have an event	18 60%	20 66.7%	38 63.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AM Dose Sunitinib Malate
	Comments	95% CI calculated based on the method of Brookmeyer and Crowley. Median reported is progression free survival weeks.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	median
	Estimated Value	27.0
	Confidence Interval	() 95%; 22.0 to 73.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PM Dose Sunitinib Malate
	Comments	95% CI calculated based on the method of Brookmeyer and Crowley.Median reported is progression free survival weeks.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	median
	Estimated Value	35.1
	Confidence Interval	() 95%; 24.4 to 51.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Total (Equals AM Plus PM Dose) Sunitinib Malate
	Comments	95% CI calculated based on the method of Brookmeyer and Crowley.Median reported is progression free survival weeks.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	median
	Estimated Value	33.6
	Confidence Interval	() 95%; 24.1 to 49.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Time to Tumor Progression (TTP)
Description	TTP was defined as the time from the date of first dose of study medication to the date of first documentation of objective tumor progression that occurred on treatment including within 28 days after the last dose of study medication.
Time Frame	Planned duration on this protocol of up to 1 year

Outcome Measure Data

Analysis Population Description

ITT population (all subjects enrolled that received at least 1 dose of study medication) with measurable disease at baseline and correct histological cancer type.

Arm/Group Title	AM Dose Sunitinib Malate	PM Dose Sunitinib Malate	Total (Equals AM Plus PM Dose) Sunitinib Malate
Arm/Group Description	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.
Measure Participants	30	30	60
Patient was censored	18 60%	13 43.3%	31 51.7%
Patient observed to have an event	12 40%	17 56.7%	29 48.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AM Dose Sunitinib Malate
	Comments	95% CI calculated based on the method of Brookmeyer and Crowley.Time to progression in weeks reported as median.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	median
	Estimated Value	57
	Confidence Interval	() 95%; 24.1 to 73.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PM Dose Sunitinib Malate
	Comments	95% CI calculated based on the method of Brookmeyer and Crowley.Time to progression in weeks reported as median.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	median
	Estimated Value	42.1
	Confidence Interval	() 95%; 26.1 to 65.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Total (Equals AM Plus PM Dose) Sunitinib Malate
	Comments	95% CI calculated based on the method of Brookmeyer and Crowley.Time to progression in weeks reported as median.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	median
	Estimated Value	42.1
	Confidence Interval	() 95%; 26.1 to 65.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Duration of Tumor Response (DR) [Descriptive Statistics]
Description	DR was defined as the time from the date of first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the date of the first documentation of objective tumor progression or to death due to any cause that occurred within 28 days after the last dose of study medication, whichever occurred first.
Time Frame	Planned duration on this protocol of up to 1 year

Outcome Measure Data

Analysis Population Description

ITT population (all subjects enrolled that received at least 1 dose of study medication) with measurable disease at baseline and correct histological cancer type. Number of responders (AM=3, PM=5, Total=8)

Arm/Group Title	AM Dose Sunitinib Malate	PM Dose Sunitinib Malate	Total (Equals AM Plus PM Dose) Sunitinib Malate
Arm/Group Description	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.
Measure Participants	30	30	60
Median (Full Range) [weeks]	32.7	40.3	33.9

8. Secondary Outcome

Title	Overall Survival (OS) and One-year Survival [Descriptive Statistics]
Description	Overall survival is defined as time from the date of first dose of study medication to the date of death due to any cause. One year survival rate defined as the probability that a patient is alive 1 year after the date of first study medication.
Time Frame	Survival status was collected by telephone contact every 2 months for up to 2 years from study entry.

Outcome Measure Data

Analysis Population Description

ITT population (all subjects enrolled that received at least 1 dose of study medication).

Arm/Group Title	AM Dose Sunitinib Malate	PM Dose Sunitinib Malate	Total (Equals AM Plus PM Dose) Sunitinib Malate
Arm/Group Description	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.
Measure Participants	30	30	60
Number of subjects alive	16 53.3%	17 56.7%	33 55%
Number of subjects dead	14 46.7%	13 43.3%	27 45%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AM Dose Sunitinib Malate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	1 year survival rate
	Estimated Value	60.0
	Confidence Interval	() 95%; 40.5 to 75.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PM Dose Sunitinib Malate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	1 year survival rate
	Estimated Value	79.7
	Confidence Interval	() 95%; 60.3 to 90.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Total (Equals AM Plus PM Dose) Sunitinib Malate
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	1 year survival rate
	Estimated Value	69.7
	Confidence Interval	() 95%; 56.3 to 79.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Score of FACIT-Fatigue Scale
Description	FACIT-Fatigue Scale: Overall score from 13-question questionnaire (measures fatigue/asthenia for patients with chronic, life-threatening illnesses). For each question, patient rates condition for the past week on a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). Maximum, minimum mean included data available for >=10 subjects.
Time Frame	Baseline, Day 1 & 15 of each treatment cycle

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	AM Dose Sunitinib Malate	PM Dose Sunitinib Malate	Total (Equals AM Plus PM Dose) Sunitinib Malate
Arm/Group Description	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.
Measure Participants	30	30	60
Baseline Score	35.9 (11.13)	36.3 (13.69)	36.1 (12.35)
Maximum Post-Baseline Score	40.6 (10.38)	42.8 (8.61)	41.7 (9.50)
Minimum Post-Baseline Score	26.9 (12.39)	26.0 (13.87)	26.4 (13.06)

10. Secondary Outcome

Title	Score of EQ-VAS (Euro Quality of Life -Visual Analog Scale)
Description	EQ-VAS score on the self-rated "thermometer," indicating the patient's own assessment of their health status from 0 (worst) to 100 (best) imaginable health state. Change: median score at observation minus median score at baseline. Maximum changes (Increase or Decrease from baseline) included data available for >=10 subjects.
Time Frame	Baseline, Day 1 &15 of each treatment cycle up to 1 year on study

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	AM Dose Sunitinib Malate	PM Dose Sunitinib Malate	Total (Equals AM Plus PM Dose) Sunitinib Malate
Arm/Group Description	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.
Measure Participants	30	30	60
Maximum Increase	7.5	10.0	18.0
Maximum Decrease	0.0	-10.0	-7.5

11. Secondary Outcome

Title	Score of EQ-5D (Euro Quality of Life-5 Dimension) Weighted Health Index
Description	EQ-5D: health status in 5 dimensions (mobility, self-care, pain/discomfort, anxiety/depression, usual activities) with a weighted health Index based on general population values where 0.0 = death and 1.0 = perfect health. Change: median index score at observation minus median index score at baseline (includes data available for >=10 subjects).
Time Frame	Baseline, Day 1 & 15 of each treatment cycle up to 1 year on study

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	AM Dose Sunitinib Malate	PM Dose Sunitinib Malate	Total (Equals AM Plus PM Dose) Sunitinib Malate
Arm/Group Description	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.
Measure Participants	30	30	60
Maximum Increase	0.1	0.0	0.1
Maximum Decrease	-0.1	-0.8	-0.1

Adverse Events

Arm/Group Title	AM Dose Sunitinib Malate		PM Dose Sunitinib Malate
Arm/Group Description	Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.		Subjects received sunitinib malate at a starting dose of 37.5 mg/day in repeated 4-week cycles and cycles could be repeated for up to 1 year in the absence of any withdrawal criteria. Subjects were randomized to receive either morning (AM) or afternoon (PM) dose. Doses could be increased to 50 mg daily.
All Cause Mortality
	AM Dose Sunitinib Malate		PM Dose Sunitinib Malate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	AM Dose Sunitinib Malate		PM Dose Sunitinib Malate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/ (NaN)		12/ (NaN)
Blood and lymphatic system disorders
Anaemia	3/30 (10%)		0/30 (0%)
Gastrointestinal disorders
Vomiting	4/30 (13.3%)		1/30 (3.3%)
Diarrhoea	3/30 (10%)		0/30 (0%)
Nausea	2/30 (6.7%)		1/30 (3.3%)
Gastrointestinal haemorrhage	1/30 (3.3%)		1/30 (3.3%)
Abdominal pain	0/30 (0%)		1/30 (3.3%)
Abdominal wall haemorrhage	1/30 (3.3%)		0/30 (0%)
Constipation	0/30 (0%)		1/30 (3.3%)
Dental caries	0/30 (0%)		1/30 (3.3%)
Gastrointestinal perforation	1/30 (3.3%)		0/30 (0%)
Intestinal obstruction	0/30 (0%)		1/30 (3.3%)
Oesophagitis haemorrhagic	0/30 (0%)		1/30 (3.3%)
Peritonitis	1/30 (3.3%)		0/30 (0%)
Pneumatosis intestinalis	0/30 (0%)		1/30 (3.3%)
General disorders
Disease progression	1/30 (3.3%)		3/30 (10%)
Asthenia	3/30 (10%)		0/30 (0%)
General physical health deterioration	3/30 (10%)		0/30 (0%)
Pyrexia	0/30 (0%)		2/30 (6.7%)
Chest pain	0/30 (0%)		1/30 (3.3%)
Chills	0/30 (0%)		1/30 (3.3%)
Death	1/30 (3.3%)		0/30 (0%)
Fatigue	1/30 (3.3%)		0/30 (0%)
Hernia pain	1/30 (3.3%)		0/30 (0%)
Infections and infestations
Wound infection	1/30 (3.3%)		1/30 (3.3%)
Catheter related infection	0/30 (0%)		1/30 (3.3%)
Emphysematous cystitis	0/30 (0%)		1/30 (3.3%)
Pyelonephritis	0/30 (0%)		1/30 (3.3%)
Sepsis	0/30 (0%)		1/30 (3.3%)
Septic shock	1/30 (3.3%)		0/30 (0%)
Urinary tract infection	0/30 (0%)		1/30 (3.3%)
Urinary tract infection staphylococcal	1/30 (3.3%)		0/30 (0%)
Investigations
Blood thyroid stimulating hormone increased	1/30 (3.3%)		0/30 (0%)
Weight decreased	0/30 (0%)		1/30 (3.3%)
Metabolism and nutrition disorders
Dehydration	1/30 (3.3%)		1/30 (3.3%)
Anorexia	1/30 (3.3%)		0/30 (0%)
Cachexia	1/30 (3.3%)		0/30 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/30 (0%)		1/30 (3.3%)
Pain in extremity	1/30 (3.3%)		0/30 (0%)
Nervous system disorders
Cerebrovascular accident	0/30 (0%)		1/30 (3.3%)
Syncope	1/30 (3.3%)		0/30 (0%)
Transient ischaemic attack	0/30 (0%)		1/30 (3.3%)
Psychiatric disorders
Confusional state	1/30 (3.3%)		0/30 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/30 (3.3%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	AM Dose Sunitinib Malate		PM Dose Sunitinib Malate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/ (NaN)		30/ (NaN)
Blood and lymphatic system disorders
Anaemia	15/30 (50%)		14/30 (46.7%)
Neutropenia	9/30 (30%)		9/30 (30%)
Thrombocytopenia	7/30 (23.3%)		6/30 (20%)
Leukopenia	4/30 (13.3%)		2/30 (6.7%)
Lymphopenia	1/30 (3.3%)		0/30 (0%)
Macrocytosis	1/30 (3.3%)		0/30 (0%)
Cardiac disorders
Angina pectoris	0/30 (0%)		1/30 (3.3%)
Palpitations	1/30 (3.3%)		0/30 (0%)
Ear and labyrinth disorders
Ear pain	1/30 (3.3%)		2/30 (6.7%)
Vertigo	2/30 (6.7%)		1/30 (3.3%)
Endocrine disorders
Hypothyroidism	4/30 (13.3%)		4/30 (13.3%)
Hyperthyroidism	1/30 (3.3%)		1/30 (3.3%)
Eye disorders
Eyelash discolouration	1/30 (3.3%)		3/30 (10%)
Conjunctival haemorrhage	1/30 (3.3%)		0/30 (0%)
Conjunctivitis	1/30 (3.3%)		0/30 (0%)
Diplopia	1/30 (3.3%)		0/30 (0%)
Eye pruritus	0/30 (0%)		1/30 (3.3%)
Eye swelling	1/30 (3.3%)		0/30 (0%)
Eyelid oedema	1/30 (3.3%)		0/30 (0%)
Vision blurred	1/30 (3.3%)		0/30 (0%)
Gastrointestinal disorders
Diarrhoea	17/30 (56.7%)		10/30 (33.3%)
Abdominal pain	11/30 (36.7%)		13/30 (43.3%)
Nausea	11/30 (36.7%)		10/30 (33.3%)
Vomiting	14/30 (46.7%)		7/30 (23.3%)
Abdominal pain upper	5/30 (16.7%)		8/30 (26.7%)
Constipation	8/30 (26.7%)		5/30 (16.7%)
Stomatitis	7/30 (23.3%)		6/30 (20%)
Gastrooesophageal reflux disease	4/30 (13.3%)		4/30 (13.3%)
Flatulence	3/30 (10%)		2/30 (6.7%)
Abdominal distension	2/30 (6.7%)		2/30 (6.7%)
Abdominal discomfort	2/30 (6.7%)		1/30 (3.3%)
Abdominal pain lower	0/30 (0%)		3/30 (10%)
Dyspepsia	2/30 (6.7%)		1/30 (3.3%)
Oral pain	1/30 (3.3%)		2/30 (6.7%)
Dry mouth	1/30 (3.3%)		1/30 (3.3%)
Gastrointestinal haemorrhage	1/30 (3.3%)		1/30 (3.3%)
Gingival bleeding	2/30 (6.7%)		0/30 (0%)
Gingival pain	1/30 (3.3%)		1/30 (3.3%)
Glossodynia	2/30 (6.7%)		0/30 (0%)
Rectal haemorrhage	0/30 (0%)		2/30 (6.7%)
Toothache	1/30 (3.3%)		1/30 (3.3%)
Abdominal wall haemorrhage	1/30 (3.3%)		0/30 (0%)
Anal fissure	1/30 (3.3%)		0/30 (0%)
Anal pruritus	1/30 (3.3%)		0/30 (0%)
Ascites	1/30 (3.3%)		0/30 (0%)
Cheilitis	1/30 (3.3%)		0/30 (0%)
Dental caries	0/30 (0%)		1/30 (3.3%)
Dysphagia	0/30 (0%)		1/30 (3.3%)
Enterocutaneous fistula	0/30 (0%)		1/30 (3.3%)
Faeces discoloured	1/30 (3.3%)		0/30 (0%)
Food poisoning	1/30 (3.3%)		0/30 (0%)
Gastritis	1/30 (3.3%)		0/30 (0%)
Gastrointestinal perforation	1/30 (3.3%)		0/30 (0%)
Haemorrhoids	0/30 (0%)		1/30 (3.3%)
Intestinal obstruction	0/30 (0%)		1/30 (3.3%)
Lip swelling	0/30 (0%)		1/30 (3.3%)
Oesophagitis	0/30 (0%)		1/30 (3.3%)
Oesophagitis haemorrhagic	0/30 (0%)		1/30 (3.3%)
Peritonitis	1/30 (3.3%)		0/30 (0%)
Pneumatosis intestinalis	0/30 (0%)		1/30 (3.3%)
Stomach discomfort	1/30 (3.3%)		0/30 (0%)
Subileus	1/30 (3.3%)		0/30 (0%)
Tongue ulceration	1/30 (3.3%)		0/30 (0%)
General disorders
Asthenia	13/30 (43.3%)		10/30 (33.3%)
Fatigue	12/30 (40%)		10/30 (33.3%)
Mucosal inflammation	3/30 (10%)		8/30 (26.7%)
Oedema peripheral	8/30 (26.7%)		3/30 (10%)
Pyrexia	5/30 (16.7%)		6/30 (20%)
Chills	3/30 (10%)		4/30 (13.3%)
Chest pain	1/30 (3.3%)		4/30 (13.3%)
General physical health deterioration	5/30 (16.7%)		0/30 (0%)
Disease progression	1/30 (3.3%)		3/30 (10%)
Pain	0/30 (0%)		3/30 (10%)
Death	1/30 (3.3%)		0/30 (0%)
Face oedema	1/30 (3.3%)		0/30 (0%)
Feeling hot	0/30 (0%)		1/30 (3.3%)
Hernia pain	1/30 (3.3%)		0/30 (0%)
Temperature intolerance	1/30 (3.3%)		0/30 (0%)
Hepatobiliary disorders
Liver disorder	1/30 (3.3%)		1/30 (3.3%)
Hepatomegaly	0/30 (0%)		1/30 (3.3%)
Infections and infestations
Nasopharyngitis	3/30 (10%)		1/30 (3.3%)
Urinary tract infection	1/30 (3.3%)		2/30 (6.7%)
Herpes zoster	1/30 (3.3%)		1/30 (3.3%)
Wound infection	1/30 (3.3%)		1/30 (3.3%)
Bronchitis	0/30 (0%)		1/30 (3.3%)
Catheter related infection	0/30 (0%)		1/30 (3.3%)
Emphysematous cystitis	0/30 (0%)		1/30 (3.3%)
Folliculitis	1/30 (3.3%)		0/30 (0%)
Incision site cellulitis	1/30 (3.3%)		0/30 (0%)
Laryngitis	1/30 (3.3%)		0/30 (0%)
Pneumonia	1/30 (3.3%)		0/30 (0%)
Pyelonephritis	0/30 (0%)		1/30 (3.3%)
Sepsis	0/30 (0%)		1/30 (3.3%)
Septic shock	1/30 (3.3%)		0/30 (0%)
Tooth infection	1/30 (3.3%)		0/30 (0%)
Upper respiratory tract infection	0/30 (0%)		1/30 (3.3%)
Urinary tract infection staphylococcal	1/30 (3.3%)		0/30 (0%)
Vaginal infection	0/30 (0%)		1/30 (3.3%)
Injury, poisoning and procedural complications
Contusion	1/30 (3.3%)		0/30 (0%)
Fall	1/30 (3.3%)		0/30 (0%)
Joint injury	0/30 (0%)		1/30 (3.3%)
Muscle strain	0/30 (0%)		1/30 (3.3%)
Investigations
Blood thyroid stimulating hormone increased	5/30 (16.7%)		4/30 (13.3%)
Weight decreased	2/30 (6.7%)		4/30 (13.3%)
Blood alkaline phosphatase increased	3/30 (10%)		2/30 (6.7%)
Aspartate aminotransferase increased	2/30 (6.7%)		2/30 (6.7%)
Gamma-glutamyltransferase increased	3/30 (10%)		1/30 (3.3%)
Alanine aminotransferase increased	1/30 (3.3%)		2/30 (6.7%)
Blood creatinine increased	2/30 (6.7%)		0/30 (0%)
Alanine aminotransferase	0/30 (0%)		1/30 (3.3%)
Blood bilirubin increased	0/30 (0%)		1/30 (3.3%)
Blood potassium decreased	1/30 (3.3%)		0/30 (0%)
Blood urea increased	1/30 (3.3%)		0/30 (0%)
Breath sounds absent	0/30 (0%)		1/30 (3.3%)
Mean cell haemoglobin increased	1/30 (3.3%)		0/30 (0%)
Mean cell volume abnormal	1/30 (3.3%)		0/30 (0%)
Metabolism and nutrition disorders
Anorexia	8/30 (26.7%)		7/30 (23.3%)
Hypoalbuminaemia	3/30 (10%)		5/30 (16.7%)
Hypokalaemia	2/30 (6.7%)		2/30 (6.7%)
Hypophosphataemia	2/30 (6.7%)		1/30 (3.3%)
Decreased appetite	2/30 (6.7%)		0/30 (0%)
Dehydration	1/30 (3.3%)		1/30 (3.3%)
Hyperkalaemia	1/30 (3.3%)		1/30 (3.3%)
Cachexia	1/30 (3.3%)		0/30 (0%)
Hyperglycaemia	0/30 (0%)		1/30 (3.3%)
Hypocalcaemia	1/30 (3.3%)		0/30 (0%)
Hyponatraemia	1/30 (3.3%)		0/30 (0%)
Musculoskeletal and connective tissue disorders
Back pain	7/30 (23.3%)		6/30 (20%)
Pain in extremity	9/30 (30%)		2/30 (6.7%)
Arthralgia	5/30 (16.7%)		2/30 (6.7%)
Muscle spasms	4/30 (13.3%)		3/30 (10%)
Musculoskeletal pain	3/30 (10%)		2/30 (6.7%)
Myalgia	2/30 (6.7%)		3/30 (10%)
Bone pain	2/30 (6.7%)		0/30 (0%)
Flank pain	0/30 (0%)		1/30 (3.3%)
Muscle fatigue	1/30 (3.3%)		0/30 (0%)
Muscular weakness	0/30 (0%)		1/30 (3.3%)
Neck pain	1/30 (3.3%)		0/30 (0%)
Nodule on extremity	1/30 (3.3%)		0/30 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	1/30 (3.3%)		0/30 (0%)
Nervous system disorders
Headache	8/30 (26.7%)		6/30 (20%)
Dysgeusia	3/30 (10%)		2/30 (6.7%)
Ageusia	2/30 (6.7%)		1/30 (3.3%)
Dizziness	2/30 (6.7%)		1/30 (3.3%)
Hyperaesthesia	1/30 (3.3%)		1/30 (3.3%)
Hypogeusia	2/30 (6.7%)		0/30 (0%)
Neuropathy peripheral	2/30 (6.7%)		0/30 (0%)
Paraesthesia	1/30 (3.3%)		1/30 (3.3%)
Amnesia	0/30 (0%)		1/30 (3.3%)
Cerebrovascular accident	0/30 (0%)		1/30 (3.3%)
Formication	1/30 (3.3%)		0/30 (0%)
Psychomotor skills impaired	1/30 (3.3%)		0/30 (0%)
Somnolence	1/30 (3.3%)		0/30 (0%)
Syncope	1/30 (3.3%)		0/30 (0%)
Transient ischaemic attack	0/30 (0%)		1/30 (3.3%)
Tremor	0/30 (0%)		1/30 (3.3%)
Psychiatric disorders
Depression	3/30 (10%)		2/30 (6.7%)
Insomnia	3/30 (10%)		1/30 (3.3%)
Anxiety	0/30 (0%)		2/30 (6.7%)
Confusional state	1/30 (3.3%)		0/30 (0%)
Renal and urinary disorders
Dysuria	1/30 (3.3%)		2/30 (6.7%)
Pollakiuria	1/30 (3.3%)		2/30 (6.7%)
Renal impairment	1/30 (3.3%)		1/30 (3.3%)
Renal pain	2/30 (6.7%)		0/30 (0%)
Urinary tract disorder	1/30 (3.3%)		1/30 (3.3%)
Haematuria	1/30 (3.3%)		0/30 (0%)
Nephrotic syndrome	0/30 (0%)		1/30 (3.3%)
Proteinuria	0/30 (0%)		1/30 (3.3%)
Renal failure	0/30 (0%)		1/30 (3.3%)
Urinary incontinence	1/30 (3.3%)		0/30 (0%)
Reproductive system and breast disorders
Breast pain	1/30 (3.3%)		1/30 (3.3%)
Vaginal haemorrhage	2/30 (6.7%)		0/30 (0%)
Menorrhagia	1/30 (3.3%)		0/30 (0%)
Metrorrhagia	1/30 (3.3%)		0/30 (0%)
Pelvic pain	0/30 (0%)		1/30 (3.3%)
Vulvovaginal burning sensation	1/30 (3.3%)		0/30 (0%)
Vulvovaginal dryness	0/30 (0%)		1/30 (3.3%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	7/30 (23.3%)		5/30 (16.7%)
Dyspnoea	3/30 (10%)		4/30 (13.3%)
Cough	0/30 (0%)		5/30 (16.7%)
Pharyngolaryngeal pain	1/30 (3.3%)		2/30 (6.7%)
Dry throat	1/30 (3.3%)		0/30 (0%)
Dyspnoea exertional	0/30 (0%)		1/30 (3.3%)
Haemoptysis	1/30 (3.3%)		0/30 (0%)
Hiccups	0/30 (0%)		1/30 (3.3%)
Nasal dryness	1/30 (3.3%)		0/30 (0%)
Pulmonary embolism	0/30 (0%)		1/30 (3.3%)
Throat irritation	1/30 (3.3%)		0/30 (0%)
Throat tightness	1/30 (3.3%)		0/30 (0%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome	8/30 (26.7%)		7/30 (23.3%)
Hair colour changes	7/30 (23.3%)		6/30 (20%)
Rash	6/30 (20%)		2/30 (6.7%)
Dry skin	4/30 (13.3%)		2/30 (6.7%)
Eczema	1/30 (3.3%)		5/30 (16.7%)
Yellow skin	3/30 (10%)		3/30 (10%)
Pruritus	4/30 (13.3%)		0/30 (0%)
Alopecia	1/30 (3.3%)		2/30 (6.7%)
Skin discolouration	1/30 (3.3%)		2/30 (6.7%)
Skin ulcer	2/30 (6.7%)		1/30 (3.3%)
Dermatitis	1/30 (3.3%)		1/30 (3.3%)
Hyperhidrosis	1/30 (3.3%)		1/30 (3.3%)
Periorbital oedema	0/30 (0%)		2/30 (6.7%)
Acne	1/30 (3.3%)		0/30 (0%)
Blister	1/30 (3.3%)		0/30 (0%)
Dermal cyst	1/30 (3.3%)		0/30 (0%)
Erythema	1/30 (3.3%)		0/30 (0%)
Increased tendency to bruise	1/30 (3.3%)		0/30 (0%)
Ingrowing nail	1/30 (3.3%)		0/30 (0%)
Nail disorder	1/30 (3.3%)		0/30 (0%)
Rash macular	1/30 (3.3%)		0/30 (0%)
Skin reaction	0/30 (0%)		1/30 (3.3%)
Urticaria	1/30 (3.3%)		0/30 (0%)
Surgical and medical procedures
Sinus operation	1/30 (3.3%)		0/30 (0%)
Vascular disorders
Hypertension	10/30 (33.3%)		8/30 (26.7%)
Capillary fragility	0/30 (0%)		1/30 (3.3%)
Hypertensive crisis	0/30 (0%)		1/30 (3.3%)
Pallor	0/30 (0%)		1/30 (3.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Pfizer has the right to review disclosure, requesting a delay of < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential info other than study results.