A Pivotal Study Of SU011248 In The Treatment Of Patients With Cytokine-Refractory Metastatic Renal Cell Carcinoma.

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00077974
• Collaborator: (none)
• Enrollment: 106
• Locations: 15
• Arm: 1
• Duration (Months): 55
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To assess the safety and efficacy of SU011248 in patients with metastatic, refractory renal cell carcinoma

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Renal Cell	Drug: SU011248	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 106 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pivotal Study Of SU011248 In The Treatment Of Patients With Cytokine-Refractory Metastatic Renal Cell Carcinoma
• Study Start Date: Feb 1, 2004
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: SU011248; 50-mg orally taken daily for 4 weeks and off treatment for 2 weeks until progression or unacceptable toxicity; Other Names: Sunitinib, SUTENT

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors(RECIST) [From start of study treatment until Day 28 of Cycles 1-5, Day 28 of even Cycles thereafter]

   Overall confirmed objective response = confirmed Complete Response (CR) or confirmed Partial Response (PR) according to RECIST. CR defined as disappearance of all target lesions. PR defined as >= 30 percent 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. Time to Tumor Progression (TTP) [From start of study treatment until Day 28 of Cycles 1-5, Day 28 of even Cycles thereafter]

   Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to cancer, whichever comes first. TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]).

2. Duration of Response (DR) [Day 28 of Cycles 1-5, Day 28 of even Cycles thereafter or death due to cancer]

   Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of patients with a confirmed objective tumor response.

3. Overall Survival (OS) [From start of study treatment until death]

   Time in weeks from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the subject current status was death).

4. Progression-free Survival (PFS) [From start of study treatment until Day 28 of Cycles 1-5, Day 28 of even Cycles thereafter or death]

   Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").

5. Percent Chance of Patient Survival [From start of study treatment until death]

   Probability of survival 1 year and 2 years after the first dose of study treatment

6. Observed Plasma Trough Concentrations of Sunitinib [Day 28 of Cycle 1 through 4, Day 1 of Cycles 5 and greater]

   Observed plasma trough (predose) (Cmin) concentrations of sunitinib

7. Observed Plasma Trough Concentrations of Sunitinib Metabolite [Day 28 of Cycle 1 through 4, Day 1 of Cycles 5 and greater]

   Observed plasma trough (predose) (Cmin) concentrations of sunitinib metabolite (SU012662)

8. Observed Plasma Trough Concentrations of Sunitinib Plus Metabolite [Day 28 of Cycle 1 through 4, Day 1 of Cycles 5 and greater]

   Observed plasma trough (predose) concentrations of sunitinib plus its metabolite (SU012662)

9. Dose Corrected Plasma Trough Concentrations of Sunitinib [Day 28 of Cycle 1 through 4, Day 1 of Cycles 5 and greater]

   Dose corrected plasma trough (predose) (Cmin) concentrations of sunitinib. Dose-corrected trough concentrations were set to missing for trough samples collected outside acceptable times from dose administration, samples not collected within scheduled day range, samples with missing collection or administration dates or times, samples collected with dose interruption, and samples collected with inconsistent dose level within 10 days of last dose date.

10. Dose Corrected Plasma Trough Concentrations of Sunitinib Metabolite [Day 28 of Cycle 1 through 4, Day 1 of Cycles 5 and greater]

    Dose corrected plasma trough (predose) (Cmin) concentrations of sunitinib metabolite (SU012662). Dose-corrected trough concentrations were set to missing for trough samples collected outside acceptable times from dose administration, samples not collected within scheduled day range, samples with missing collection or administration dates or times, samples collected with dose interruption, and samples collected with inconsistent dose level within 10 days of last dose date.

11. Dose Corrected Plasma Trough Concentrations of Sunitinib Plus Metabolite [Day 28 of Cycle 1 through 4, Day 1 of Cycles 5 and greater]

    Dose corrected plasma trough (predose) (Cmin) concentrations of sunitinib plus its metabolite (SU012662). Dose-corrected trough concentrations were set to missing for trough samples collected outside acceptable times from dose administration, samples not collected within scheduled day range, samples with missing collection or administration dates or times, samples collected with dose interruption, and samples collected with inconsistent dose level within 10 days of last dose date.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Cytokine refractory metastatic renal cell carcinoma with clear cell component

• Radiographic evidence of disease progression during or within 9 months of completion of 1 cytokine therapy

• Prior nephrectomy

Exclusion Criteria:

• Prior treatment with any systemic therapy other than 1 cytokine therapy

• History of or known brain metastases

• Uncontrolled hypertension or other significant cardiac events within the 12 months prior to study start

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Duarte	California	United States	91010-3000
2	Pfizer Investigational Site	Pasadena	California	United States	91105
3	Pfizer Investigational Site	San Francisco	California	United States	94115
4	Pfizer Investigational Site	Boston	Massachusetts	United States	02114
5	Pfizer Investigational Site	Boston	Massachusetts	United States	02115
6	Pfizer Investigational Site	Boston	Massachusetts	United States	02215
7	Pfizer Investigational Site	Ann Arbor	Michigan	United States	48109
8	Pfizer Investigational Site	Rochester	Minnesota	United States	55905
9	Pfizer Investigational Site	New York	New York	United States	10021
10	Pfizer Investigational Site	New York	New York	United States	10022
11	Pfizer Investigational Site	Durham	North Carolina	United States	27705
12	Pfizer Investigational Site	Cleveland	Ohio	United States	44195
13	Pfizer Investigational Site	Portland	Oregon	United States	97213
14	Pfizer Investigational Site	Philadelphia	Pennsylvania	United States	19111
15	Pfizer Investigational Site	Madison	Wisconsin	United States	53792

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: NCT00077974
• Other Study ID Numbers: A6181006; NCT00082849
• First Posted: Feb 18, 2004
• Last Update Posted: Oct 13, 2010
• Last Verified: Oct 1, 2010

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

Study Results

Participant Flow

Arm/Group Title	Sunitinib Malate
Arm/Group Description	50 milligrams per day on Schedule 4/2 (4 weeks daily treatment followed by 2 weeks off treatment in repeated 6-week cycles)
Period Title: Overall Study
STARTED	106
COMPLETED	2
NOT COMPLETED	104

Baseline Characteristics

Arm/Group Title	Sunitinib Malate
Arm/Group Description	50 milligrams per day on Schedule 4/2 (4 weeks daily treatment followed by 2 weeks off treatment in repeated 6-week cycles)
Overall Participants	106
Age, Customized (participants) [Number]
< 65 years	87 82.1%
>= 65 years	19 17.9%
Sex: Female, Male (Count of Participants)
Female	39 36.8%
Male	67 63.2%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors(RECIST)
Description	Overall confirmed objective response = confirmed Complete Response (CR) or confirmed Partial Response (PR) according to RECIST. CR defined as disappearance of all target lesions. PR defined as >= 30 percent decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time Frame	From start of study treatment until Day 28 of Cycles 1-5, Day 28 of even Cycles thereafter

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population included all subjects who enrolled in the study that received at least 1 dose of study medication. This was the primary population for all efficacy analyses and safety analyses.

Arm/Group Title	Sunitinib Malate
Arm/Group Description	50 milligrams per day on Schedule 4/2 (4 weeks daily treatment followed by 2 weeks off treatment in repeated 6-week cycles)
Measure Participants	106
Number [participants]	35 33%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	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	Percent
	Estimated Value	33
	Confidence Interval	() 95%; 24.2 to 42.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Using exact method based on binomial distribution. Percent equals n divided by N times 100.

2. Secondary Outcome

Title	Time to Tumor Progression (TTP)
Description	Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to cancer, whichever comes first. TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]).
Time Frame	From start of study treatment until Day 28 of Cycles 1-5, Day 28 of even Cycles thereafter

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Sunitinib Malate
Arm/Group Description	50 milligrams per day on Schedule 4/2 (4 weeks daily treatment followed by 2 weeks off treatment in repeated 6-week cycles)
Measure Participants	106
Median (95% Confidence Interval) [weeks]	46.3

3. Secondary Outcome

Title	Duration of Response (DR)
Description	Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of patients with a confirmed objective tumor response.
Time Frame	Day 28 of Cycles 1-5, Day 28 of even Cycles thereafter or death due to cancer

Outcome Measure Data

Analysis Population Description

ITT subgroup of patients with a confirmed objective tumor response

Arm/Group Title	Sunitinib Malate
Arm/Group Description	50 milligrams per day on Schedule 4/2 (4 weeks daily treatment followed by 2 weeks off treatment in repeated 6-week cycles)
Measure Participants	35
Median (95% Confidence Interval) [weeks]	60.4

4. Secondary Outcome

Title	Overall Survival (OS)
Description	Time in weeks from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the subject current status was death).
Time Frame	From start of study treatment until death

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Sunitinib Malate
Arm/Group Description	50 milligrams per day on Schedule 4/2 (4 weeks daily treatment followed by 2 weeks off treatment in repeated 6-week cycles)
Measure Participants	106
Median (95% Confidence Interval) [weeks]	104.1

5. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").
Time Frame	From start of study treatment until Day 28 of Cycles 1-5, Day 28 of even Cycles thereafter or death

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Sunitinib Malate
Arm/Group Description	50 milligrams per day on Schedule 4/2 (4 weeks daily treatment followed by 2 weeks off treatment in repeated 6-week cycles)
Measure Participants	106
Median (95% Confidence Interval) [weeks]	38.0

6. Secondary Outcome

Title	Percent Chance of Patient Survival
Description	Probability of survival 1 year and 2 years after the first dose of study treatment
Time Frame	From start of study treatment until death

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Sunitinib Malate
Arm/Group Description	50 milligrams per day on Schedule 4/2 (4 weeks daily treatment followed by 2 weeks off treatment in repeated 6-week cycles)
Measure Participants	106
1 year	67.2
2 years	50.2

7. Secondary Outcome

Title	Observed Plasma Trough Concentrations of Sunitinib
Description	Observed plasma trough (predose) (Cmin) concentrations of sunitinib
Time Frame	Day 28 of Cycle 1 through 4, Day 1 of Cycles 5 and greater

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis population

Arm/Group Title	Sunitinib Malate
Arm/Group Description	50 milligrams per day on Schedule 4/2 (4 weeks daily treatment followed by 2 weeks off treatment in repeated 6-week cycles)
Measure Participants	104
Cycle 1 Day 28 (n = 103)	46.82 (24.19)
Cycle 2 Day 28 (n = 81)	50.13 (24.66)
Cycle 3 Day 28 (n = 73)	49.36 (25.26)
Cycle 4 Day 28 (n = 66)	53.18 (22.62)
Cycle 5 Day 1 (n = 63)	1.55 (1.48)
Cycle 6 Day 1 (n = 59)	1.44 (1.37)
Cycle 7 Day 1 (n = 52)	1.51 (1.90)
Cycle 8 Day 1 (n = 48)	1.60 (1.38)
Cycle 9 Day 1 (n = 46)	1.60 (1.58)
Cycle 10 Day 1 (n = 41)	1.69 (1.97)
Cycle 11 Day 1 (n = 38)	2.05 (3.00)
Cycle 12 Day 1 (n = 34)	1.72 (1.66)
Cycle 13 Day 1 (n = 30)	1.74 (1.57)
Cycle 14 Day 1 (n = 30)	1.60 (1.45)
Cycle 15 Day 1 (n = 24)	1.56 (2.17)
Cycle 16 Day 1 (n = 24)	1.46 (1.23)
Cycle 17 Day 1 (n = 19)	1.42 (1.65)
Cycle 18 Day 1 (n = 16)	2.20 (2.17)
Cycle 19 Day 1 (n = 14)	1.34 (1.18)
Cycle 20 Day 1 (n = 12)	2.96 (3.53)
Cycle 21 Day 1 (n = 11)	2.53 (2.07)
Cycle 22 Day 1 (n = 11)	2.18 (2.57)
Cycle 23 Day 1 (n = 7)	3.14 (2.70)
Cycle 24 Day 1 (n = 7)	2.75 (1.86)
Cycle 25 Day 1 (n = 6)	1.99 (1.37)
Cycle 26 Day 1 (n = 6)	2.46 (2.43)
Cycle 27 Day 1 (n = 6)	1.20 (1.21)
Cycle 28 Day 1 (n = 4)	1.75 (1.61)
Cycle 29 Day 1 (n = 5)	2.93 (3.64)
Cycle 30 Day 1 (n = 4)	1.02 (0.90)

8. Secondary Outcome

Title	Observed Plasma Trough Concentrations of Sunitinib Metabolite
Description	Observed plasma trough (predose) (Cmin) concentrations of sunitinib metabolite (SU012662)
Time Frame	Day 28 of Cycle 1 through 4, Day 1 of Cycles 5 and greater

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis population

Arm/Group Title	Sunitinib Malate
Arm/Group Description	50 milligrams per day on Schedule 4/2 (4 weeks daily treatment followed by 2 weeks off treatment in repeated 6-week cycles)
Measure Participants	106
Cycle 1 Day 28 (n = 103)	26.44 (15.66)
Cycle 2 Day 28 (n = 81)	28.21 (17.21)
Cycle 3 Day 28 (n = 73)	28.32 (18.38)
Cycle 4 Day 28 (n = 66)	28.54 (16.93)
Cycle 5 Day 1 (n = 63)	2.50 (1.60)
Cycle 6 Day 1 (n = 59)	2.64 (1.67)
Cycle 7 Day 1 (n = 52)	2.64 (1.98)
Cycle 8 Day 1 (n = 48)	2.66 (1.68)
Cycle 9 Day 1 (n = 46)	2.81 (2.32)
Cycle 10 Day 1 (n = 41)	2.54 (1.87)
Cycle 11 Day 1 (n = 38)	2.78 (3.40)
Cycle 12 Day 1 (n = 34)	2.67 (2.29)
Cycle 13 Day 1 (n = 30)	2.77 (2.03)
Cycle 14 Day 1 (n = 30)	2.49 (2.05)
Cycle 15 Day 1 (n = 24)	2.51 (2.98)
Cycle 16 Day 1 (n = 24)	2.30 (1.84)
Cycle 17 Day 1 (n = 19)	1.83 (1.49)
Cycle 18 Day 1 (n = 16)	2.16 (1.07)
Cycle 19 Day 1 (n = 14)	2.06 (1.82)
Cycle 20 Day 1 (n = 12)	2.92 (1.86)
Cycle 21 Day 1 (n = 11)	3.13 (2.19)
Cycle 22 Day 1 (n = 11)	3.24 (3.12)
Cycle 23 Day 1 (n = 7)	3.10 (2.25)
Cycle 24 Day 1 (n = 7)	2.64 (1.68)
Cycle 25 Day 1 (n = 6)	1.99 (1.07)
Cycle 26 Day 1 (n = 6)	2.60 (2.26)
Cycle 27 Day 1 (n = 6)	1.36 (1.22)
Cycle 28 Day 1 (n = 4)	1.81 (1.20)
Cycle 29 Day 1 (n = 5)	2.43 (2.12)
Cycle 30 Day 1 (n = 4)	1.10 (0.73)

9. Secondary Outcome

Title	Observed Plasma Trough Concentrations of Sunitinib Plus Metabolite
Description	Observed plasma trough (predose) concentrations of sunitinib plus its metabolite (SU012662)
Time Frame	Day 28 of Cycle 1 through 4, Day 1 of Cycles 5 and greater

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis population

Arm/Group Title	Sunitinib Malate
Arm/Group Description	50 milligrams per day on Schedule 4/2 (4 weeks daily treatment followed by 2 weeks off treatment in repeated 6-week cycles)
Measure Participants	106
Cycle 1 Day 28 (n = 103)	73.26 (36.85)
Cycle 2 Day 28 (n = 81)	78.34 (39.03)
Cycle 3 Day 28 (n = 73)	77.68 (39.84)
Cycle 4 Day 28 (n = 66)	81.71 (36.55)
Cycle 5 Day 1 (n = 63)	4.04 (2.80)
Cycle 6 Day 1 (n = 59)	4.08 (2.72)
Cycle 7 Day 1 (n = 52)	4.15 (3.57)
Cycle 8 Day 1 (n = 48)	4.26 (2.78)
Cycle 9 Day 1 (n = 46)	4.41 (3.65)
Cycle 10 Day 1 (n = 41)	4.23 (3.69)
Cycle 11 Day 1 (n = 38)	4.83 (6.34)
Cycle 12 Day 1 (n = 34)	4.39 (3.69)
Cycle 13 Day 1 (n = 30)	4.52 (3.36)
Cycle 14 Day 1 (n = 30)	4.09 (3.37)
Cycle 15 Day 1 (n = 24)	4.07 (5.00)
Cycle 16 Day 1 (n = 24)	3.75 (2.63)
Cycle 17 Day 1 (n = 19)	3.25 (3.03)
Cycle 18 Day 1 (n = 16)	4.35 (2.90)
Cycle 19 Day 1 (n = 14)	3.40 (2.87)
Cycle 20 Day 1 (n = 12)	5.88 (5.19)
Cycle 21 Day 1 (n = 11)	5.66 (4.09)
Cycle 22 Day 1 (n = 11)	5.43 (5.61)
Cycle 23 Day 1 (n = 7)	6.24 (4.78)
Cycle 24 Day 1 (n = 7)	5.39 (3.31)
Cycle 25 Day 1 (n = 6)	3.97 (2.32)
Cycle 26 Day 1 (n = 6)	5.06 (4.61)
Cycle 27 Day 1 (n = 6)	2.55 (2.41)
Cycle 28 Day 1 (n = 4)	3.56 (2.77)
Cycle 29 Day 1 (n = 5)	5.36 (5.74)
Cycle 30 Day 1 (n = 4)	2.13 (1.57)

10. Secondary Outcome

Title	Dose Corrected Plasma Trough Concentrations of Sunitinib
Description	Dose corrected plasma trough (predose) (Cmin) concentrations of sunitinib. Dose-corrected trough concentrations were set to missing for trough samples collected outside acceptable times from dose administration, samples not collected within scheduled day range, samples with missing collection or administration dates or times, samples collected with dose interruption, and samples collected with inconsistent dose level within 10 days of last dose date.
Time Frame	Day 28 of Cycle 1 through 4, Day 1 of Cycles 5 and greater

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis population

Arm/Group Title	Sunitinib Malate
Arm/Group Description	50 milligrams per day on Schedule 4/2 (4 weeks daily treatment followed by 2 weeks off treatment in repeated 6-week cycles)
Measure Participants	106
Cycle 1 Day 28 (n = 33)	53.64 (22.54)
Cycle 2 Day 28 (n = 26)	55.94 (25.52)
Cycle 3 Day 28 (n = 20)	69.44 (33.21)
Cycle 4 Day 28 (n = 25)	64.33 (41.46)
Cycle 5 Day 1 (n = 28)	1.94 (3.24)
Cycle 6 Day 1 (n = 41)	2.15 (2.94)
Cycle 7 Day 1 (n = 35)	2.04 (4.10)
Cycle 8 Day 1 (n = 32)	2.32 (2.77)
Cycle 9 Day 1 (n = 32)	2.07 (2.62)
Cycle 10 Day 1 (n = 32)	2.68 (4.32)
Cycle 11 Day 1 (n = 25)	3.42 (6.86)
Cycle 12 Day 1 (n = 28)	1.94 (1.63)
Cycle 13 Day 1 (n = 23)	2.23 (2.49)
Cycle 14 Day 1 (n = 24)	2.41 (2.46)
Cycle 15 Day 1 (n = 16)	1.58 (1.09)
Cycle 16 Day 1 (n = 18)	2.42 (2.48)
Cycle 17 Day 1 (n = 17)	2.23 (2.66)
Cycle 18 Day 1 (n = 14)	3.05 (4.57)
Cycle 19 Day 1 (n = 11)	1.92 (1.58)
Cycle 20 Day 1 (n = 11)	5.09 (7.47)
Cycle 21 Day 1 (n = 8)	3.41 (3.24)
Cycle 22 Day 1 (n = 9)	3.91 (5.45)
Cycle 23 Day 1 (n = 6)	4.53 (3.89)
Cycle 24 Day 1 (n = 6)	3.82 (3.68)
Cycle 25 Day 1 (n = 5)	3.14 (3.24)
Cycle 26 Day 1 (n = 5)	4.09 (5.70)
Cycle 27 Day 1 (n = 5)	2.12 (2.58)
Cycle 28 Day 1 (n = 4)	2.97 (3.36)
Cycle 29 Day 1 (n = 4)	4.02 (5.60)
Cycle 30 Day 1 (n = 3)	1.36 (1.50)

11. Secondary Outcome

Title	Dose Corrected Plasma Trough Concentrations of Sunitinib Metabolite
Description	Dose corrected plasma trough (predose) (Cmin) concentrations of sunitinib metabolite (SU012662). Dose-corrected trough concentrations were set to missing for trough samples collected outside acceptable times from dose administration, samples not collected within scheduled day range, samples with missing collection or administration dates or times, samples collected with dose interruption, and samples collected with inconsistent dose level within 10 days of last dose date.
Time Frame	Day 28 of Cycle 1 through 4, Day 1 of Cycles 5 and greater

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis population

Arm/Group Title	Sunitinib Malate
Arm/Group Description	50 milligrams per day on Schedule 4/2 (4 weeks daily treatment followed by 2 weeks off treatment in repeated 6-week cycles)
Measure Participants	106
Cycle 1 Day 28 (n = 33)	31.85 (18.15)
Cycle 2 Day 28 (n = 26)	28.15 (19.80)
Cycle 3 Day 28 (n = 20)	40.53 (20.38)
Cycle 4 Day 28 (n = 25)	38.04 (24.29)
Cycle 5 Day 1 (n = 28)	2.99 (2.55)
Cycle 6 Day 1 (n = 41)	3.35 (2.52)
Cycle 7 Day 1 (n = 35)	3.11 (3.13)
Cycle 8 Day 1 (n = 32)	3.37 (2.34)
Cycle 9 Day 1 (n = 32)	3.45 (2.80)
Cycle 10 Day 1 (n = 32)	3.61 (3.62)
Cycle 11 Day 1 (n = 25)	4.37 (8.13)
Cycle 12 Day 1 (n = 28)	3.24 (2.82)
Cycle 13 Day 1 (n = 23)	3.68 (2.79)
Cycle 14 Day 1 (n = 24)	3.54 (2.60)
Cycle 15 Day 1 (n = 16)	2.80 (1.82)
Cycle 16 Day 1 (n = 18)	3.40 (2.27)
Cycle 17 Day 1 (n = 17)	2.55 (2.23)
Cycle 18 Day 1 (n = 14)	2.59 (1.69)
Cycle 19 Day 1 (n = 11)	2.93 (2.33)
Cycle 20 Day 1 (n = 11)	4.53 (3.82)
Cycle 21 Day 1 (n = 8)	3.97 (2.78)
Cycle 22 Day 1 (n = 9)	5.31 (6.73)
Cycle 23 Day 1 (n = 6)	4.26 (3.16)
Cycle 24 Day 1 (n = 6)	3.62 (2.49)
Cycle 25 Day 1 (n = 5)	3.00 (2.18)
Cycle 26 Day 1 (n = 5)	4.49 (5.29)
Cycle 27 Day 1 (n = 5)	2.36 (2.57)
Cycle 28 Day 1 (n = 4)	2.94 (2.63)
Cycle 29 Day 1 (n = 4)	3.32 (3.28)
Cycle 30 Day 1 (n = 3)	1.18 (1.08)

12. Secondary Outcome

Title	Dose Corrected Plasma Trough Concentrations of Sunitinib Plus Metabolite
Description	Dose corrected plasma trough (predose) (Cmin) concentrations of sunitinib plus its metabolite (SU012662). Dose-corrected trough concentrations were set to missing for trough samples collected outside acceptable times from dose administration, samples not collected within scheduled day range, samples with missing collection or administration dates or times, samples collected with dose interruption, and samples collected with inconsistent dose level within 10 days of last dose date.
Time Frame	Day 28 of Cycle 1 through 4, Day 1 of Cycles 5 and greater

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis population

Arm/Group Title	Sunitinib Malate
Arm/Group Description	50 milligrams per day on Schedule 4/2 (4 weeks daily treatment followed by 2 weeks off treatment in repeated 6-week cycles)
Measure Participants	106
Cycle 1 Day 28 (n = 33)	85.49 (37.49)
Cycle 2 Day 28 (n = 26)	84.09 (42.11)
Cycle 3 Day 28 (n = 20)	109.97 (48.38)
Cycle 4 Day 28 (n = 25)	102.37 (62.69)
Cycle 5 Day 1 (n = 28)	4.93 (5.49)
Cycle 6 Day 1 (n = 41)	5.50 (5.14)
Cycle 7 Day 1 (n = 35)	5.15 (6.97)
Cycle 8 Day 1 (n = 32)	5.69 (4.86)
Cycle 9 Day 1 (n = 32)	5.52 (5.22)
Cycle 10 Day 1 (n = 32)	6.29 (7.80)
Cycle 11 Day 1 (n = 25)	7.78 (14.94)
Cycle 12 Day 1 (n = 28)	5.19 (4.08)
Cycle 13 Day 1 (n = 23)	5.91 (5.03)
Cycle 14 Day 1 (n = 24)	5.95 (4.80)
Cycle 15 Day 1 (n = 16)	4.39 (2.48)
Cycle 16 Day 1 (n = 18)	5.82 (4.21)
Cycle 17 Day 1 (n = 17)	4.78 (4.79)
Cycle 18 Day 1 (n = 14)	5.64 (6.01)
Cycle 19 Day 1 (n = 11)	4.85 (3.77)
Cycle 20 Day 1 (n = 11)	9.63 (11.00)
Cycle 21 Day 1 (n = 8)	7.38 (5.80)
Cycle 22 Day 1 (n = 9)	9.23 (12.13)
Cycle 23 Day 1 (n = 6)	8.79 (6.77)
Cycle 24 Day 1 (n = 6)	7.44 (5.84)
Cycle 25 Day 1 (n = 5)	6.13 (5.29)
Cycle 26 Day 1 (n = 5)	8.58 (10.94)
Cycle 27 Day 1 (n = 5)	4.48 (5.14)
Cycle 28 Day 1 (n = 4)	5.90 (5.96)
Cycle 29 Day 1 (n = 4)	7.34 (8.85)
Cycle 30 Day 1 (n = 3)	2.54 (2.58)

Adverse Events

Arm/Group Title	Sunitinib Malate
Arm/Group Description	50 milligrams per day on Schedule 4/2 (4 weeks daily treatment followed by 2 weeks off treatment in repeated 6-week cycles)
All Cause Mortality
	Sunitinib Malate
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sunitinib Malate
	Affected / at Risk (%)	# Events
Total	46/106 (43.4%)
Blood and lymphatic system disorders
Anaemia	2/106 (1.9%)
Thrombocytopenia	1/106 (0.9%)
Cardiac disorders
Acute myocardial infarction	2/106 (1.9%)
Cardiac failure congestive	1/106 (0.9%)
Myocardial infarction	2/106 (1.9%)
Myocardial ischaemia	1/106 (0.9%)
Endocrine disorders
Adrenocortical insufficiency acute	1/106 (0.9%)
Gastrointestinal disorders
Abdominal pain	1/106 (0.9%)
Diarrhoea	1/106 (0.9%)
Intestinal obstruction	1/106 (0.9%)
Nausea	1/106 (0.9%)
Pancreatitis	1/106 (0.9%)
Rectal haemorrhage	1/106 (0.9%)
Stomatitis	1/106 (0.9%)
Vomiting	2/106 (1.9%)
General disorders
Disease progression	7/106 (6.6%)
Fatigue	1/106 (0.9%)
Impaired healing	1/106 (0.9%)
Non-cardiac chest pain	2/106 (1.9%)
Oedema peripheral	1/106 (0.9%)
Hepatobiliary disorders
Portal vein thrombosis	1/106 (0.9%)
Infections and infestations
Abscess	1/106 (0.9%)
Anorectal infection	1/106 (0.9%)
Clostridium difficile colitis	1/106 (0.9%)
Gastroenteritis viral	1/106 (0.9%)
Infection	2/106 (1.9%)
Pancreatic abscess	1/106 (0.9%)
Perirectal abscess	1/106 (0.9%)
Pneumonia	3/106 (2.8%)
Sepsis	1/106 (0.9%)
Staphylococcal infection	1/106 (0.9%)
Urinary tract infection	1/106 (0.9%)
Injury, poisoning and procedural complications
Femur fracture	1/106 (0.9%)
Skeletal injury	1/106 (0.9%)
Investigations
Ejection fraction decreased	1/106 (0.9%)
International normalised ratio increased	1/106 (0.9%)
Oxygen saturation decreased	1/106 (0.9%)
Platelet count decreased	1/106 (0.9%)
Metabolism and nutrition disorders
Dehydration	5/106 (4.7%)
Failure to thrive	1/106 (0.9%)
Hypercalcaemia	1/106 (0.9%)
Hyperglycaemia	1/106 (0.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/106 (1.9%)
Musculoskeletal pain	1/106 (0.9%)
Osteonecrosis	2/106 (1.9%)
Nervous system disorders
Convulsion	1/106 (0.9%)
Hypoglycaemic encephalopathy	1/106 (0.9%)
Reversible posterior leukoencephalopathy syndrome	1/106 (0.9%)
Speech disorder	1/106 (0.9%)
Spinal cord compression	2/106 (1.9%)
Syncope	1/106 (0.9%)
Psychiatric disorders
Depression	1/106 (0.9%)
Mental status changes	2/106 (1.9%)
Renal and urinary disorders
Renal failure	3/106 (2.8%)
Renal failure acute	2/106 (1.9%)
Ureteric obstruction	1/106 (0.9%)
Reproductive system and breast disorders
Uterine haemorrhage	1/106 (0.9%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/106 (1.9%)
Pleural effusion	2/106 (1.9%)
Pneumothorax	1/106 (0.9%)
Pulmonary embolism	1/106 (0.9%)
Skin and subcutaneous tissue disorders
Petechiae	1/106 (0.9%)
Purpura	1/106 (0.9%)
Surgical and medical procedures
Fracture treatment	1/106 (0.9%)
Tumour excision	1/106 (0.9%)
Vascular disorders
Aortic stenosis	1/106 (0.9%)
Other (Not Including Serious) Adverse Events
	Sunitinib Malate
	Affected / at Risk (%)	# Events
Total	106/106 (100%)
Blood and lymphatic system disorders
Anaemia	19/106 (17.9%)
Neutropenia	11/106 (10.4%)
Thrombocytopenia	11/106 (10.4%)
Endocrine disorders
Hypothyroidism	21/106 (19.8%)
Eye disorders
Lacrimation increased	7/106 (6.6%)
Gastrointestinal disorders
Abdominal discomfort	7/106 (6.6%)
Abdominal pain	19/106 (17.9%)
Abdominal pain upper	10/106 (9.4%)
Constipation	40/106 (37.7%)
Diarrhoea	67/106 (63.2%)
Dry mouth	10/106 (9.4%)
Dyspepsia	49/106 (46.2%)
Dysphagia	7/106 (6.6%)
Flatulence	11/106 (10.4%)
Gastrooesophageal reflux disease	12/106 (11.3%)
Glossodynia	11/106 (10.4%)
Haematochezia	6/106 (5.7%)
Haemorrhoids	9/106 (8.5%)
Nausea	66/106 (62.3%)
Oral pain	12/106 (11.3%)
Stomatitis	43/106 (40.6%)
Vomiting	51/106 (48.1%)
General disorders
Chest discomfort	7/106 (6.6%)
Chest pain	18/106 (17%)
Chills	20/106 (18.9%)
Fatigue	84/106 (79.2%)
Mucosal inflammation	28/106 (26.4%)
Oedema	10/106 (9.4%)
Oedema peripheral	22/106 (20.8%)
Pain	13/106 (12.3%)
Pyrexia	19/106 (17.9%)
Infections and infestations
Nasopharyngitis	10/106 (9.4%)
Sinusitis	9/106 (8.5%)
Upper respiratory tract infection	22/106 (20.8%)
Urinary tract infection	9/106 (8.5%)
Investigations
Aspartate aminotransferase increased	6/106 (5.7%)
Blood creatinine increased	9/106 (8.5%)
Ejection fraction decreased	19/106 (17.9%)
Haemoglobin decreased	8/106 (7.5%)
Lipase increased	12/106 (11.3%)
Neutrophil count decreased	11/106 (10.4%)
Platelet count decreased	16/106 (15.1%)
Weight decreased	18/106 (17%)
Weight increased	7/106 (6.6%)
White blood cell count decreased	12/106 (11.3%)
Metabolism and nutrition disorders
Anorexia	43/106 (40.6%)
Dehydration	11/106 (10.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	24/106 (22.6%)
Back pain	27/106 (25.5%)
Bone pain	13/106 (12.3%)
Flank pain	9/106 (8.5%)
Muscle spasms	10/106 (9.4%)
Muscular weakness	8/106 (7.5%)
Musculoskeletal chest pain	12/106 (11.3%)
Musculoskeletal pain	14/106 (13.2%)
Myalgia	21/106 (19.8%)
Pain in extremity	37/106 (34.9%)
Nervous system disorders
Dizziness	19/106 (17.9%)
Dysgeusia	54/106 (50.9%)
Headache	32/106 (30.2%)
Hypoaesthesia	7/106 (6.6%)
Paraesthesia	10/106 (9.4%)
Peripheral sensory neuropathy	6/106 (5.7%)
Psychiatric disorders
Anxiety	10/106 (9.4%)
Depression	12/106 (11.3%)
Insomnia	14/106 (13.2%)
Renal and urinary disorders
Dysuria	10/106 (9.4%)
Respiratory, thoracic and mediastinal disorders
Cough	26/106 (24.5%)
Dysphonia	7/106 (6.6%)
Dyspnoea	27/106 (25.5%)
Dyspnoea exertional	12/106 (11.3%)
Epistaxis	25/106 (23.6%)
Haemoptysis	9/106 (8.5%)
Nasal congestion	7/106 (6.6%)
Oropharyngeal pain	11/106 (10.4%)
Productive cough	8/106 (7.5%)
Skin and subcutaneous tissue disorders
Alopecia	14/106 (13.2%)
Blister	10/106 (9.4%)
Dry skin	23/106 (21.7%)
Erythema	15/106 (14.2%)
Hair colour changes	21/106 (19.8%)
Hyperhidrosis	6/106 (5.7%)
Palmar-plantar erythrodysaesthesia syndrome	30/106 (28.3%)
Periorbital oedema	12/106 (11.3%)
Pruritus	8/106 (7.5%)
Rash	38/106 (35.8%)
Skin discolouration	35/106 (33%)
Skin exfoliation	12/106 (11.3%)
Skin lesion	10/106 (9.4%)
Skin reaction	8/106 (7.5%)
Vascular disorders
Hot flush	7/106 (6.6%)
Hypertension	38/106 (35.8%)

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 information other than study results.