Study Of SU011248 (Sunitinib) Given In A Continuous Daily Regimen In Patients With Advanced Renal Cell Cancer

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00137423
• Collaborator: (none)
• Enrollment: 107
• Locations: 10
• Arm: 1
• Duration (Months): 36
• Patients Per Site: 10.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

To evaluate the anti-tumor activity of SU011248 (sunitinib) in cytokine-refractory metastatic renal cell carcinoma (RCC) when administered in a continuous treatment regimen

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Renal Cell Metastasis	Drug: SU011248 (sunitinib)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 107 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 Cytokine-Refractory Metastatic Renal Cell Carcinoma
• Study Start Date: May 1, 2005
• Actual Primary Completion Date: Sep 1, 2007
• Actual Study Completion Date: May 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SU011248 (sunitinib) Single-arm study	Drug: SU011248 (sunitinib); 37.5 mg/day, oral, continuous daily dosing

Outcome Measures

Primary Outcome Measures

1. Objective Response (Complete Response[CR] + Partial Response[PR]) in Subjects [4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation includes 28 day post study follow up]

   Confirmed objective responses using RECIST criteria defined as responses persisting on repeat imaging study for 2 assessments with at least 4 weeks between, and evaluating all target and non-target sites followed since baseline. Two PRs separated by an SD or NE visit in between was considered a confirmed response if the 2 PRs were > 4 weeks apart. CR=disappearance of all target lesions. PR is a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.

Secondary Outcome Measures

1. Duration of Tumor Response [4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation includes 28 day post study follow up]

   Using RECIST criteria: date of 1st objective tumor response (CR or PR) subsequently confirmed to date of 1st objective tumor progression or to death due to any cause within 28 days after last dose of study medication, whichever was first. Censored on day after the date of the last oncologic assessment documenting no tumor progression.

2. Time to Tumor Progression (TTP) [4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation includes 28 day post study follow up]

   Time from date of first dose of study medication to date of first documentation of objective tumor progression using RECIST criteria that occurred on treatment including within 28 days after the last dose of study medication. TTP censored on the day following the date of last oncologic assessment documenting absence of tumor progression. TTP based on the number of subjects with measurable disease at baseline, the correct histological cancer type, and had disease that was refractory to prior cytokine-based therapy(105 in total group).

3. Progression Free Survival (PFS) [4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation includes 28 day post study follow up]

   Using RECIST criteria: Time from date 1st dose study medication to date 1st documentation of objective tumor progression or death due to any cause occurring on treatment including within 28 days after last dose, whichever occurred 1st. Censored on day following the date of last oncologic assessment documenting absence of tumor progression. PFS based on the number of subjects with measurable disease at baseline, the correct histological cancer type, and had disease that was refractory to prior cytokine-based therapy(105 in total group).

4. Overall Survival [4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation includes 28 day post study follow up]

   Overall survival is time from the date of first dose of medication to the date of death due to any cause

5. Summary of FACIT Fatigue Scale Overall Score [Day 1 and day 15 of each treatment cycle from cycle 1 to cycle 4; day 1 of each treatment cycle after cycle 4 up to one year.]

   FACIT Fatigue Scale: Overall score from 13-questionnaire, which measures fatigue / asthenia for patients with chronic, life-threatening illnesses. For each question, a patient rates his / her condition for the past week on a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). Higher scores always represent less fatigue / asthenia. Outcome based on completed questionnaires.

6. Change From Baseline in Euro-QoL Five Dimension (EQ-5D) Weighted Health Index [Day 1 and day 15 of each treatment cycle from cycle 1 to cycle 4; day 1 of each treatment cycle after cycle 4 up to one year.]

   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.

7. Change From Baseline in EuroQoL Visual Analog Scale (EQ-VAS) Overall Health Thermometer Score [Day 1 and day 15 of each treatment cycle from cycle 1 to cycle 4; day 1 of each treatment cycle after cycle 4 up to one year.]

   EQ-VAS score on the self-rated "thermometer" indicated 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).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically proven renal cell carcinoma with metastases.

• Evidence of unidimensionally measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST).

• Failure of 1 prior cytokine-based therapy for metastatic disease. Patients treated with IFN-á alone must have received IFN-á for at least 4 weeks.

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

• Resolution of all acute toxic effects of prior therapy or surgical procedures to grade

• Adequate organ function

Exclusion Criteria:

• Prior treatment with any systemic therapy other than 1 cytokine-based therapy.

• Previous treatment on a SU011248 (sunitinib) clinical trial.

• Major surgery, radiation therapy, or systemic therapy within 4 weeks of starting the study treatment.

• Diagnosis of any second malignancy within the last 3 years, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma that has 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 on screening Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan.

• 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 cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy).

• Ongoing treatment with therapeutic doses of Coumadin (however, low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed).

• Known human immunodeficiency virus (HIV) infection.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Stanford	California	United States	94305
2	Pfizer Investigational Site	Las Vegas	Nevada	United States	89135
3	Pfizer Investigational Site	Villejuif		France	94805
4	Pfizer Investigational Site	Berlin		Germany	10117
5	Pfizer Investigational Site	Muenchen		Germany	81664
6	Pfizer Investigational Site	Thessaloniki		Greece	56429
7	Pfizer Investigational Site	Nijmegen	Gld	Netherlands	6525 GA
8	Pfizer Investigational Site	Lund		Sweden	SE-221 85
9	Pfizer Investigational Site	Stockholm		Sweden	171 76
10	Pfizer Investigational Site	St. Gallen		Switzerland	CH-9007

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: NCT00137423
• Other Study ID Numbers: A6181061
• First Posted: Aug 29, 2005
• Last Update Posted: Sep 30, 2009
• Last Verified: Sep 1, 2009

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Sunitinib

Study Results

Participant Flow

Recruitment Details	Patients must have failed 1 prior cytokine-based therapy for metastatic renal cell carcinoma and had to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Pre-assignment Detail	ECOG performance status definition 0=fully active, able to carry on all pre-disease activities without restriction 1= restricted in physically strenuous activity but ambulatory & able to carry out work of a light or sedentary nature (eg light house work or office work)

Arm/Group Title	AM Dose Sunitinib Malate (SU011248)	PM Dose Sunitinib Malate (SU011248)
Arm/Group Description	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the morning repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.Per the statistical analysis plan, the primary outcome of objective response was evaluated in patients who had measurable disease at baseline, the correct histological cancer type, & were refractory to prior cytokine-based therapy. Of 107 subjects enrolled, 2 patients did not have measurable disease at baseline, and therefore, were excluded from the analysis.	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the evening repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.Per the statistical analysis plan, the primary outcome of objective response was evaluated in patients who had measurable disease at baseline, the correct histological cancer type, & were refractory to prior cytokine-based therapy. Of 107 subjects enrolled, 2 patients did not have measurable disease at baseline, and therefore, were excluded from the analysis.
Period Title: Overall Study
STARTED	54	53
COMPLETED	15	9
NOT COMPLETED	39	44

Baseline Characteristics

Arm/Group Title	AM Dose Sunitinib Malate (SU011248)	PM Dose Sunitinib Malate (SU011248)	Total
Arm/Group Description	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the morning repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.Per the statistical analysis plan, the primary outcome of objective response was evaluated in patients who had measurable disease at baseline, the correct histological cancer type, & were refractory to prior cytokine-based therapy. Of 107 subjects enrolled, 2 patients did not have measurable disease at baseline, and therefore, were excluded from the analysis.	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the evening repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.Per the statistical analysis plan, the primary outcome of objective response was evaluated in patients who had measurable disease at baseline, the correct histological cancer type, & were refractory to prior cytokine-based therapy. Of 107 subjects enrolled, 2 patients did not have measurable disease at baseline, and therefore, were excluded from the analysis.	Total of all reporting groups
Overall Participants	54	53	107
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.3 (9.27)	57.2 (11.48)	58.2 (10.43)
Sex: Female, Male (Count of Participants)
Female	8 14.8%	11 20.8%	19 17.8%
Male	46 85.2%	42 79.2%	88 82.2%

Outcome Measures

1. Primary Outcome

Title	Objective Response (Complete Response[CR] + Partial Response[PR]) in Subjects
Description	Confirmed objective responses using RECIST criteria defined as responses persisting on repeat imaging study for 2 assessments with at least 4 weeks between, and evaluating all target and non-target sites followed since baseline. Two PRs separated by an SD or NE visit in between was considered a confirmed response if the 2 PRs were > 4 weeks apart. CR=disappearance of all target lesions. PR is a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time Frame	4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation includes 28 day post study follow up

Outcome Measure Data

Analysis Population Description

ITT; CR,PR calculated from patients with measurable disease at baseline+correct histological cancer type+ refractory to prior cytokine-based therapy n= 53,52 (AM,PM)

Arm/Group Title	AM Dose Sunitinib Malate (SU011248)	PM Dose Sunitinib Malate (SU011248)
Arm/Group Description	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the morning repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the evening repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.
Measure Participants	54	53
Number [participants]	15 27.8%	6 11.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AM Dose Sunitinib Malate (SU011248)
	Comments	Objective response rate required a sample size of 100 to test null hypothesis that true response rate was <=5% versus alternative hypothesis that true response rate was >=15% with 90% power and alpha level of 0.05. If number of OR> =11 null hypothesis that true response rate was <=5% could be rejected with a target α error rate of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Objective Response Rate
	Estimated Value	28.3
	Confidence Interval	() 95%; 16.8 to 42.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PM Dose Sunitinib Malate (SU011248)
	Comments	Objective response rate required a sample size of 100 to test null hypothesis that true response rate was <=5% versus alternative hypothesis that true response rate was >=15% with 90% power and alpha level of 0.05. If number of OR> =11 null hypothesis that true response rate was <=5% could be rejected with a target α error rate of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Objective Response Rate
	Estimated Value	11.5
	Confidence Interval	() 95%; 4.4 to 23.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Duration of Tumor Response
Description	Using RECIST criteria: date of 1st objective tumor response (CR or PR) subsequently confirmed to date of 1st objective tumor progression or to death due to any cause within 28 days after last dose of study medication, whichever was first. Censored on day after the date of the last oncologic assessment documenting no tumor progression.
Time Frame	4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation includes 28 day post study follow up

Outcome Measure Data

Analysis Population Description

ITT; DR time from start of 1st documentation of objective tumor response to 1st documentation of objective tumor progression or death & calculated for the subgroup of subjects with a confirmed objective tumor response. Descriptive statistics for responders who had an event. Total number responders n= 15,6(AM,PM). Response duration n=7,3(AM,PM).

Arm/Group Title	AM Dose Sunitinib Malate (SU011248)	PM Dose Sunitinib Malate (SU011248)
Arm/Group Description	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the morning repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the evening repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.
Measure Participants	54	53
Median (Full Range) [weeks]	24.0	32.0

3. Secondary Outcome

Title	Time to Tumor Progression (TTP)
Description	Time from date of first dose of study medication to date of first documentation of objective tumor progression using RECIST criteria that occurred on treatment including within 28 days after the last dose of study medication. TTP censored on the day following the date of last oncologic assessment documenting absence of tumor progression. TTP based on the number of subjects with measurable disease at baseline, the correct histological cancer type, and had disease that was refractory to prior cytokine-based therapy(105 in total group).
Time Frame	4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation includes 28 day post study follow up

Outcome Measure Data

Analysis Population Description

ITT;TTP calculated based on subgroup with baseline disease assessment, measurable disease at baseline, correct histological type and refractory to cytokine.Estimates based on Kaplan-Meier method with 95% CI calculated based on Brookmeyer and Crowley. n=53,52(AM,PM).

Arm/Group Title	AM Dose Sunitinib Malate (SU011248)	PM Dose Sunitinib Malate (SU011248)
Arm/Group Description	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the morning repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the evening repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.
Measure Participants	54	53
Median (95% Confidence Interval) [weeks]	35.7	35.9

4. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Using RECIST criteria: Time from date 1st dose study medication to date 1st documentation of objective tumor progression or death due to any cause occurring on treatment including within 28 days after last dose, whichever occurred 1st. Censored on day following the date of last oncologic assessment documenting absence of tumor progression. PFS based on the number of subjects with measurable disease at baseline, the correct histological cancer type, and had disease that was refractory to prior cytokine-based therapy(105 in total group).
Time Frame	4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation includes 28 day post study follow up

Outcome Measure Data

Analysis Population Description

ITT; Calculation based on subgroup of patients with baseline disease assessment, measurable disease at baseline, correct histological type and are refractory to cytokine. Estimates based on Kaplan-Meier method with 95% CI calculated based on Brookmeyer and Crowley. N=53,52(AM,PM).

Arm/Group Title	AM Dose Sunitinib Malate (SU011248)	PM Dose Sunitinib Malate (SU011248)
Arm/Group Description	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the morning repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the evening repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.
Measure Participants	54	53
Median (95% Confidence Interval) [weeks]	35.7	35.3

5. Secondary Outcome

Title	Overall Survival
Description	Overall survival is time from the date of first dose of medication to the date of death due to any cause
Time Frame	4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation includes 28 day post study follow up

Outcome Measure Data

Analysis Population Description

ITT; Patients who are alive at the time of analysis or who are lost to follow up are censored on the last date they were known to be alive. Estimates are based on the Kaplan-Meier method with 95% CI calculated based on Brookmeyer and Crowley method. n=54,53(AM,PM).

Arm/Group Title	AM Dose Sunitinib Malate (SU011248)	PM Dose Sunitinib Malate (SU011248)
Arm/Group Description	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the morning repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the evening repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.
Measure Participants	54	53
Median (95% Confidence Interval) [weeks]	91.4	76.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AM Dose Sunitinib Malate (SU011248)
	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	77.4
	Confidence Interval	() 95%; 63.6 to 86.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	valid presentation only if at least 1 patient has overall survival >=1 year. Based on normal approximation, 95% CI will be derived by log transformation of the cumulative hazard rate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PM Dose Sunitinib Malate (SU011248)
	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	66.0
	Confidence Interval	() 95%; 51.6 to 77.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	valid presentation only if at least 1 patient has overall survival >=1 year. Based on normal approximation, 95% CI will be derived by log transformation of the cumulative hazard rate.

6. Secondary Outcome

Title	Summary of FACIT Fatigue Scale Overall Score
Description	FACIT Fatigue Scale: Overall score from 13-questionnaire, which measures fatigue / asthenia for patients with chronic, life-threatening illnesses. For each question, a patient rates his / her condition for the past week on a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). Higher scores always represent less fatigue / asthenia. Outcome based on completed questionnaires.
Time Frame	Day 1 and day 15 of each treatment cycle from cycle 1 to cycle 4; day 1 of each treatment cycle after cycle 4 up to one year.

Outcome Measure Data

Analysis Population Description

ITT; Results summarized by cohort & time point through Cycle 13 (the last cycle for which more than 3 subjects completed the questionnaire on either arm). If more than 50% of the items in the scale were answered, then missing items were imputed with the mean of the non-missing items scored at that visit. Outcome based on completed questionnaires.

Arm/Group Title	AM Dose Sunitinib Malate	PM Dose Sunitinib Malate
Arm/Group Description	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the morning repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the evening repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.Per the statistical analysis plan, the primary outcome of objective response was evaluated in patients who had measurable disease at baseline, the correct histological cancer type, & were refractory to prior cytokine-based therapy. Of 107 subjects enrolled, 2 patients did not have measurable disease at baseline, and therefore, were excluded from the analysis.
Measure Participants	54	53
Baseline Score n=52,52	39.5 (11.41)	39.6 (10.15)
Maximum Post-Baseline Score n=53,52	43.4 (7.86)	42.7 (8.19)
Minimum Post-Baseline Score n=53,52	28.0 (12.34)	29.4 (13.65)

7. Secondary Outcome

Title	Change From Baseline in Euro-QoL Five Dimension (EQ-5D) 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.
Time Frame	Day 1 and day 15 of each treatment cycle from cycle 1 to cycle 4; day 1 of each treatment cycle after cycle 4 up to one year.

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	AM Dose Sunitinib Malate (SU011248)	PM Dose Sunitinib Malate (SU011248)
Arm/Group Description	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the morning repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.Per the statistical analysis plan, the primary outcome of objective response was evaluated in patients who had measurable disease at baseline, the correct histological cancer type, & were refractory to prior cytokine-based therapy. Of 107 subjects enrolled, 2 patients did not have measurable disease at baseline, and therefore, were excluded from the analysis.	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the evening repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.Per the statistical analysis plan, the primary outcome of objective response was evaluated in patients who had measurable disease at baseline, the correct histological cancer type, & were refractory to prior cytokine-based therapy. Of 107 subjects enrolled, 2 patients did not have measurable disease at baseline, and therefore, were excluded from the analysis.
Measure Participants	54	53
Maximum Increase	0.0	0.0
Maximum Decrease	0.0	-0.1

8. Secondary Outcome

Title	Change From Baseline in EuroQoL Visual Analog Scale (EQ-VAS) Overall Health Thermometer Score
Description	EQ-VAS score on the self-rated "thermometer" indicated 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).
Time Frame	Day 1 and day 15 of each treatment cycle from cycle 1 to cycle 4; day 1 of each treatment cycle after cycle 4 up to one year.

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	AM Dose Sunitinib Malate (SU011248)	PM Dose Sunitinib Malate (SU011248)
Arm/Group Description	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the morning repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.Per the statistical analysis plan, the primary outcome of objective response was evaluated in patients who had measurable disease at baseline, the correct histological cancer type, & were refractory to prior cytokine-based therapy. Of 107 subjects enrolled, 2 patients did not have measurable disease at baseline, and therefore, were excluded from the analysis.	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the evening repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.Per the statistical analysis plan, the primary outcome of objective response was evaluated in patients who had measurable disease at baseline, the correct histological cancer type, & were refractory to prior cytokine-based therapy. Of 107 subjects enrolled, 2 patients did not have measurable disease at baseline, and therefore, were excluded from the analysis.
Measure Participants	54	53
Maximum Increase	0.0	0.0
Maximum Decrease	-10.0	-9.0

Adverse Events

Arm/Group Title	AM Dose Sunitinib Malate (SU011248)		PM Dose Sunitinib Malate (SU011248)
Arm/Group Description	Patients received a starting dose of 37.5 mg/day of sunitinib malate in the morning repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.		Patients received a starting dose of 37.5 mg/day of sunitinib malate in the evening repeated 4-week cycles continuing for up to 1 year in absence of any withdrawal criteria.
All Cause Mortality
	AM Dose Sunitinib Malate (SU011248)		PM Dose Sunitinib Malate (SU011248)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	AM Dose Sunitinib Malate (SU011248)		PM Dose Sunitinib Malate (SU011248)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/ (NaN)		20/ (NaN)
Blood and lymphatic system disorders
Thrombocytopenia	3/54 (5.6%)		1/53 (1.9%)
Anaemia	1/54 (1.9%)		2/53 (3.8%)
Cardiac disorders
Cardiac arrest	0/54 (0%)		1/53 (1.9%)
Cardiac failure congestive	0/54 (0%)		1/53 (1.9%)
Ear and labyrinth disorders
Vertigo	1/54 (1.9%)		0/53 (0%)
Eye disorders
Eye pain	0/54 (0%)		1/53 (1.9%)
Gastrointestinal disorders
Abdominal pain	4/54 (7.4%)		3/53 (5.7%)
Haematemesis	1/54 (1.9%)		2/53 (3.8%)
Vomiting	2/54 (3.7%)		1/53 (1.9%)
Nausea	0/54 (0%)		2/53 (3.8%)
Oesophagitis	1/54 (1.9%)		1/53 (1.9%)
Subileus	2/54 (3.7%)		0/53 (0%)
Constipation	0/54 (0%)		1/53 (1.9%)
Diarrhoea	0/54 (0%)		1/53 (1.9%)
Gastritis haemorrhagic	0/54 (0%)		1/53 (1.9%)
Gastrointestinal haemorrhage	1/54 (1.9%)		0/53 (0%)
Melaena	1/54 (1.9%)		0/53 (0%)
Pancreatitis acute	1/54 (1.9%)		0/53 (0%)
Salivary hypersecretion	1/54 (1.9%)		0/53 (0%)
Stomatitis	1/54 (1.9%)		0/53 (0%)
General disorders
Asthenia	1/54 (1.9%)		2/53 (3.8%)
Disease progression	0/54 (0%)		3/53 (5.7%)
Fatigue	0/54 (0%)		2/53 (3.8%)
Gait disturbance	1/54 (1.9%)		1/53 (1.9%)
Mucosal inflammation	2/54 (3.7%)		0/53 (0%)
Oedema peripheral	2/54 (3.7%)		0/53 (0%)
Pyrexia	0/54 (0%)		2/53 (3.8%)
Hypothermia	1/54 (1.9%)		0/53 (0%)
Multi-organ failure	1/54 (1.9%)		0/53 (0%)
Organ failure	0/54 (0%)		1/53 (1.9%)
Performance status decreased	0/54 (0%)		1/53 (1.9%)
Hepatobiliary disorders
Cholangitis acute	1/54 (1.9%)		0/53 (0%)
Infections and infestations
Perirectal abscess	1/54 (1.9%)		1/53 (1.9%)
Pneumonia	1/54 (1.9%)		0/53 (0%)
Respiratory tract infection	1/54 (1.9%)		0/53 (0%)
Sepsis	1/54 (1.9%)		0/53 (0%)
Urinary tract infection	1/54 (1.9%)		0/53 (0%)
Injury, poisoning and procedural complications
Burn oesophageal	1/54 (1.9%)		0/53 (0%)
Fall	1/54 (1.9%)		0/53 (0%)
Wound	1/54 (1.9%)		0/53 (0%)
Investigations
Aspiration pleural cavity	1/54 (1.9%)		0/53 (0%)
Blood creatinine increased	0/54 (0%)		1/53 (1.9%)
Metabolism and nutrition disorders
Anorexia	1/54 (1.9%)		3/53 (5.7%)
Dehydration	1/54 (1.9%)		3/53 (5.7%)
Hyperkalaemia	1/54 (1.9%)		1/53 (1.9%)
Hypoglycaemia	1/54 (1.9%)		1/53 (1.9%)
Diabetes mellitus	1/54 (1.9%)		0/53 (0%)
Hypercalcaemia	0/54 (0%)		1/53 (1.9%)
Hyperglycaemia	1/54 (1.9%)		0/53 (0%)
Hypernatraemia	0/54 (0%)		1/53 (1.9%)
Hyponatraemia	0/54 (0%)		1/53 (1.9%)
Malnutrition	1/54 (1.9%)		0/53 (0%)
Musculoskeletal and connective tissue disorders
Bone lesion	1/54 (1.9%)		0/53 (0%)
Flank pain	0/54 (0%)		1/53 (1.9%)
Muscular weakness	1/54 (1.9%)		0/53 (0%)
Osteonecrosis	1/54 (1.9%)		0/53 (0%)
Pain in extremity	1/54 (1.9%)		0/53 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	1/54 (1.9%)		0/53 (0%)
Malignant ascites	0/54 (0%)		1/53 (1.9%)
Malignant neoplasm progression	0/54 (0%)		1/53 (1.9%)
Tumour pain	0/54 (0%)		1/53 (1.9%)
Nervous system disorders
Dizziness	2/54 (3.7%)		1/53 (1.9%)
Syncope	0/54 (0%)		2/53 (3.8%)
Brain oedema	0/54 (0%)		1/53 (1.9%)
Cerebrovascular accident	0/54 (0%)		1/53 (1.9%)
Depressed level of consciousness	1/54 (1.9%)		0/53 (0%)
Dysaesthesia	1/54 (1.9%)		0/53 (0%)
Paresis	1/54 (1.9%)		0/53 (0%)
Peripheral sensory neuropathy	0/54 (0%)		1/53 (1.9%)
Psychiatric disorders
Confusional state	1/54 (1.9%)		1/53 (1.9%)
Renal and urinary disorders
Anuria	2/54 (3.7%)		0/53 (0%)
Urinary retention	1/54 (1.9%)		1/53 (1.9%)
Haematuria	0/54 (0%)		1/53 (1.9%)
Obstructive uropathy	1/54 (1.9%)		0/53 (0%)
Renal failure	0/54 (0%)		1/53 (1.9%)
Renal failure acute	0/54 (0%)		1/53 (1.9%)
Renal haemorrhage	0/54 (0%)		1/53 (1.9%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/54 (1.9%)		0/53 (0%)
Pelvic pain	1/54 (1.9%)		0/53 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/54 (3.7%)		1/53 (1.9%)
Epistaxis	2/54 (3.7%)		0/53 (0%)
Haemoptysis	2/54 (3.7%)		0/53 (0%)
Nocturnal dyspnoea	1/54 (1.9%)		0/53 (0%)
Pleural effusion	0/54 (0%)		1/53 (1.9%)
Skin and subcutaneous tissue disorders
Dermatitis allergic	0/54 (0%)		1/53 (1.9%)
Palmar-plantar erythrodysaesthesia syndrome	1/54 (1.9%)		0/53 (0%)
Surgical and medical procedures
Pleurodesis	1/54 (1.9%)		0/53 (0%)
Other (Not Including Serious) Adverse Events
	AM Dose Sunitinib Malate (SU011248)		PM Dose Sunitinib Malate (SU011248)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/ (NaN)		53/ (NaN)
Blood and lymphatic system disorders
Anaemia	7/54 (13%)		9/53 (17%)
Thrombocytopenia	8/54 (14.8%)		6/53 (11.3%)
Neutropenia	5/54 (9.3%)		7/53 (13.2%)
Leukopenia	3/54 (5.6%)		3/53 (5.7%)
Ear and labyrinth disorders
Vertigo	4/54 (7.4%)		3/53 (5.7%)
Gastrointestinal disorders
Diarrhoea	41/54 (75.9%)		40/53 (75.5%)
Stomatitis	25/54 (46.3%)		21/53 (39.6%)
Nausea	25/54 (46.3%)		19/53 (35.8%)
Dyspepsia	22/54 (40.7%)		15/53 (28.3%)
Vomiting	16/54 (29.6%)		18/53 (34%)
Abdominal pain	14/54 (25.9%)		13/53 (24.5%)
Constipation	14/54 (25.9%)		8/53 (15.1%)
Abdominal pain upper	13/54 (24.1%)		6/53 (11.3%)
Oral pain	4/54 (7.4%)		6/53 (11.3%)
Flatulence	1/54 (1.9%)		8/53 (15.1%)
Glossodynia	5/54 (9.3%)		3/53 (5.7%)
Gastrooesophageal reflux disease	0/54 (0%)		7/53 (13.2%)
Haemorrhoids	4/54 (7.4%)		3/53 (5.7%)
Rectal haemorrhage	5/54 (9.3%)		2/53 (3.8%)
Dysphagia	2/54 (3.7%)		4/53 (7.5%)
Gingival bleeding	3/54 (5.6%)		3/53 (5.7%)
General disorders
Asthenia	24/54 (44.4%)		20/53 (37.7%)
Fatigue	19/54 (35.2%)		22/53 (41.5%)
Mucosal inflammation	16/54 (29.6%)		9/53 (17%)
Pyrexia	9/54 (16.7%)		10/53 (18.9%)
Chest pain	9/54 (16.7%)		9/53 (17%)
Oedema peripheral	9/54 (16.7%)		5/53 (9.4%)
Chills	4/54 (7.4%)		3/53 (5.7%)
Infections and infestations
Nasopharyngitis	6/54 (11.1%)		4/53 (7.5%)
Bronchitis	4/54 (7.4%)		2/53 (3.8%)
Oral herpes	3/54 (5.6%)		3/53 (5.7%)
Urinary tract infection	5/54 (9.3%)		1/53 (1.9%)
Investigations
Weight decreased	15/54 (27.8%)		17/53 (32.1%)
Blood lactate dehydrogenase increased	6/54 (11.1%)		2/53 (3.8%)
Blood creatinine increased	1/54 (1.9%)		6/53 (11.3%)
Blood alkaline phosphatase increased	2/54 (3.7%)		4/53 (7.5%)
Metabolism and nutrition disorders
Anorexia	21/54 (38.9%)		20/53 (37.7%)
Dehydration	1/54 (1.9%)		8/53 (15.1%)
Vitamin B12 deficiency	6/54 (11.1%)		2/53 (3.8%)
Hyperkalaemia	3/54 (5.6%)		3/53 (5.7%)
Musculoskeletal and connective tissue disorders
Pain in extremity	11/54 (20.4%)		11/53 (20.8%)
Arthralgia	9/54 (16.7%)		8/53 (15.1%)
Back pain	8/54 (14.8%)		6/53 (11.3%)
Myalgia	2/54 (3.7%)		8/53 (15.1%)
Nervous system disorders
Dysgeusia	13/54 (24.1%)		15/53 (28.3%)
Headache	6/54 (11.1%)		8/53 (15.1%)
Dizziness	9/54 (16.7%)		4/53 (7.5%)
Ageusia	4/54 (7.4%)		7/53 (13.2%)
Psychiatric disorders
Insomnia	4/54 (7.4%)		8/53 (15.1%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	17/54 (31.5%)		11/53 (20.8%)
Cough	6/54 (11.1%)		10/53 (18.9%)
Haemoptysis	8/54 (14.8%)		6/53 (11.3%)
Dyspnoea	6/54 (11.1%)		7/53 (13.2%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome	28/54 (51.9%)		23/53 (43.4%)
Hair colour changes	18/54 (33.3%)		20/53 (37.7%)
Rash	12/54 (22.2%)		11/53 (20.8%)
Dry skin	10/54 (18.5%)		12/53 (22.6%)
Erythema	11/54 (20.4%)		8/53 (15.1%)
Skin discolouration	4/54 (7.4%)		7/53 (13.2%)
Alopecia	6/54 (11.1%)		3/53 (5.7%)
Hyperkeratosis	2/54 (3.7%)		4/53 (7.5%)
Pruritus	1/54 (1.9%)		5/53 (9.4%)
Vascular disorders
Hypertension	25/54 (46.3%)		23/53 (43.4%)
Haemorrhage	4/54 (7.4%)		4/53 (7.5%)

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 disclosures, 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.