An International Phase 2 Study Of SU011248 In Patients With Inoperable Liver Cancer

An Open Label International Multi-Center Phase 2 Activity And Safety Study Of SU011248 In Patients With Unresectable Hepatocellular Carcinoma

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00247676

Enrollment

Registered

2005-11-02

Start date

2006-02-28

Completion date

2009-02-28

Last updated

2010-02-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Liver Neoplasms, Unresectable Hepatocellular Carcinoma

Keywords

Liver neoplasms, sunitinib, Phase 2

Brief summary

The study will consist of two parts. In Part 1 the study will start enrolling 38 patients and then further 25 patients up to a total of 63 eligible patients. If the study gives good results it can be expanded to a total of 160 patients. SU011248 will be administered orally daily for 4 weeks followed by a 2-week rest at a starting dose of 50 mg \[milligrams\] with provision for dose reduction based on tolerability. All patients will receive repeated cycles of SU011248 until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met. After discontinuation of treatment, patients will be followed up in order to collect information on further antineoplastic therapy and survival

Interventions

DRUGSunitinib (SU011248)

Sunitinib 50 mg by oral capsule, daily for 4 weeks in every 6 week cycle until progression or unacceptable toxicity.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Histologically confirmed diagnosis of hepatocellular carcinoma * Patients must present with disease not amenable to curative surgery (i.e. either hepatectomy, or liver transplant). * Evidence of measurable disease by radiographic technique * Adequate organ function.

Exclusion criteria

* Prior treatment with any systemic treatment for liver cancer * Presence of clinically relevant ascites * Severe hemorrhage \<4 weeks of starting study treatment. * Diagnosis of second malignancy within last 3 years * History of or known brain metastases, spinal cord compression, or carcinomatous meningitis * Known human immunodeficiency virus (HIV) * Serious acute or chronic illness * Current treatment on another clinical trial * Pregnant or breastfeeding

Design outcomes

Primary

Measure	Time frame	Description
Best Overall Response	From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter	Number of subjects with best overall response. Complete response (CR)=disappearance of all target lesions. Partial Response (PR)= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions. Progressive disease (PD)= ≥ 20% increase in sum of longest dimensions of lesions taking as a reference smallest sum of the longest dimensions since treatment start, or the appearance of ≥ 1 new lesion. Stable disease (SD)=neither shrinkage for PR or increase for PD taking as reference smallest sum of longest dimensions since treatment start.
Objective Response (CR or PR)	From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter	Number of patients with objective response: confirmed CR or confirmed PR according to RECIST. CR was defined as the disappearance of all target lesions. A PR was defined as a ≥30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. To be assigned a status of PR or CR, changes in tumor measurements in patients with responding tumors had to have been confirmed by repeat studies that were performed ≥ 4 weeks after the criteria for response were first met.

Secondary

Measure	Time frame	Description
Best Overall Response of PR or SD With Duration ≥12 Weeks	From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or SD with duration of at least 12 weeks or death due to cancer	Number of patients with best overall response of PR or SD with duration ≥ 12 weeks. Best overall response was defined as the time from the first documentation of tumor response that was subsequently confirmed to the first documentation of disease progression or to death due to any cause. CR=disappearance of all target lesions. PR= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions. SD=neither shrinkage for PR or increase for PD taking as reference smallest sum of longest dimensions since treatment start.
Progression-Free Survival (Overall ITT)	From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death	Time from start of study treatment to first documentation of objective tumor progression, or to death due to any cause.
Progression-Free Survival (ITT Child Pugh Class A Subject Population)	From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death	Time from start of study treatment to first documentation of objective tumor progression, or to death due to any cause.
Time to Tumor Progression (Overall ITT)	From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter	Time from the start of study treatment to the first documentation of objective tumor progression.
Time to Tumor Progression (ITT Child Pugh Class A Subject Population)	From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter	Time from the start of study treatment to the first documentation of objective tumor progression.
Overall Survival (Overall ITT)	From start of study treatment until death.	Time from the date of first dose of study medication to the date of death due to any cause.
Overall Survival (ITT Child Pugh Class A Subject Population)	From start of study treatment until death.	Time from the date of first dose of study medication to the date of death due to any cause.
1-Year Survival Probability	From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter up until 1 year.	Probability of survival 1 year after the first dose of study treatment.
Trough Plasma Concentrations (Ctrough) of Sunitinib	Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)	Ctrough = the concentration prior to study drug administration.
Ctrough of SU-012662 (Metabolite of Sunitinib)	Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)	Ctrough = the concentration prior to study drug administration.
Duration of Objective Response (CR or PR)	From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death due to cancer	Time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of disease progression or to death due to any cause. CR=disappearance of all target lesions. PR= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions.
Dose-Corrected Ctrough of Sunitinib	Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)	Data was dose-corrected to the starting dose (dose-corrected Ctrough = observed Ctrough x \[starting dose/actual dose\]).
Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)	Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)	Data was dose-corrected to the starting dose (dose-corrected Ctrough = observed Ctrough x \[starting dose/actual dose\]).
Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)	Cycle 1 (Days 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)	Data was dose-corrected to the starting dose (dose-corrected Ctrough = observed Ctrough x \[starting dose/actual dose\]).
Circulating Endothelial Cells (CECs) and Circulating Endothelial Progenitor Cells (CEPs)	Cycle 1 (Days 1, 14), Cycle 2 (Days 1, 28), Cycle 5 (Day 1)	Blood samples for the assessment of CECs and circulating CEPs were planned to be obtained for subjects in Part 1 of the study, and for a subset of subjects in Part 2 of the study to complete the angiogenic profile of unresectable hepatocellular carcinoma, in addition to the soluble protein evaluation.
Tissue Tumor Markers Assessed by Tumor Biopsy	Day 28 of Cycle 1 (optional)	Provision of previously collected tumor paraffin blocks (or at least 5-10 4-micron slides prepared from the paraffin block) for correlative laboratory analysis was optional. For all subjects showing OR on study, it was highly recommended to provide previously collected paraffin blocks (or at least 5-10 4-micron slides prepared from the paraffin block). These samples were to be analyzed for markers that may be associated with tumor proliferation or angiogenesis.
Plasma Concentration of Vascular Endothelial Growth Factor (VEGF)	Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28)	Plasma concentrations of VEGF that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by e nzyme-linked immunosorbent assay (ELISA). Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
Plasma Concentration of VEGF-C	Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28)	Plasma concentrations of VEGF-C that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by ELISA. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
Plasma Concentration of Soluble VEGF Receptor-2 (sVEGFR-2)	Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28)	Plasma concentrations of sVEGFR-2 that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by ELISA. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline). Samples below the limit of quantitation and samples with insufficient volume available were excluded.
Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3)	Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28)	Plasma concentrations of sVEGFR-3 that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by ELISA. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
Plasma Concentration of Soluble KIT (sKIT)	Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28)	Plasma concentrations of sKIT that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by ELISA analysis. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
Ctrough of Total Drug (Sunitinib + SU-012662)	Cycle 1 (Days 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)	Ctrough = the concentration prior to study drug administration.
Clinical Benefit Response (CR, PR, or SD With Duration ≥12 Weeks)	From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or SD with duration of at least 12 weeks on study	Number of patients with Clinical Benefit Response: confirmed CR, confirmed PR, or SD for at least 12 weeks on study according to RECIST. CR=disappearance of all target lesions. PR= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions. SD=neither shrinkage for PR or increase for PD taking as reference smallest sum of longest dimensions since treatment start.

Countries

France, South Korea, Taiwan

Participant flow

Recruitment details

This study was designed using a Simon 2-stage design with the objective response rate as the primary efficacy endpoint. Enrollment was halted after the first stage because the minimum number of responders by Response Evaluation Criteria in Solid Tumors (RECIST) needed to continue into Stage 2 was not reached.

Participants by arm

Arm	Count
50 Milligram (mg) Sunitinib Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.	37
Total	37

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	11
Overall Study	Death	5
Overall Study	Lack of Efficacy	15
Overall Study	Other	3
Overall Study	Withdrawal by Subject	2

Baseline characteristics

Characteristic	50 Milligram (mg) Sunitinib
Age Continuous	59.0 years STANDARD_DEVIATION 12.4
Sex: Female, Male Female	3 Participants
Sex: Female, Male Male	34 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	37 / 37
serious Total, serious adverse events	24 / 37

Outcome results

Primary

Best Overall Response

Number of subjects with best overall response. Complete response (CR)=disappearance of all target lesions. Partial Response (PR)= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions. Progressive disease (PD)= ≥ 20% increase in sum of longest dimensions of lesions taking as a reference smallest sum of the longest dimensions since treatment start, or the appearance of ≥ 1 new lesion. Stable disease (SD)=neither shrinkage for PR or increase for PD taking as reference smallest sum of longest dimensions since treatment start.

Time frame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter

Population: Intent-to-treat (ITT) population includes all patients enrolled in the study that received at least 1 dose of study medication.

Arm	Measure	Group	Value (NUMBER)
50 Milligram (mg) Sunitinib	Best Overall Response	Not Evaluable	7 participants
50 Milligram (mg) Sunitinib	Best Overall Response	CR	0 participants
50 Milligram (mg) Sunitinib	Best Overall Response	PR	1 participants
50 Milligram (mg) Sunitinib	Best Overall Response	SD	15 participants
50 Milligram (mg) Sunitinib	Best Overall Response	Progressive Disease	11 participants
50 Milligram (mg) Sunitinib	Best Overall Response	Missing	3 participants

Primary

Objective Response (CR or PR)

Number of patients with objective response: confirmed CR or confirmed PR according to RECIST. CR was defined as the disappearance of all target lesions. A PR was defined as a ≥30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. To be assigned a status of PR or CR, changes in tumor measurements in patients with responding tumors had to have been confirmed by repeat studies that were performed ≥ 4 weeks after the criteria for response were first met.

Time frame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter

Population: ITT

Arm	Measure	Value (NUMBER)
50 Milligram (mg) Sunitinib	Objective Response (CR or PR)	1 participants

95% CI: [0.1, 14.2]

Secondary

1-Year Survival Probability

Probability of survival 1 year after the first dose of study treatment.

Time frame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter up until 1 year.

Population: ITT

Arm	Measure	Value (NUMBER)
50 Milligram (mg) Sunitinib	1-Year Survival Probability	0.324 Probability

95% CI: [0.168, 0.479]

Secondary

Best Overall Response of PR or SD With Duration ≥12 Weeks

Number of patients with best overall response of PR or SD with duration ≥ 12 weeks. Best overall response was defined as the time from the first documentation of tumor response that was subsequently confirmed to the first documentation of disease progression or to death due to any cause. CR=disappearance of all target lesions. PR= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions. SD=neither shrinkage for PR or increase for PD taking as reference smallest sum of longest dimensions since treatment start.

Time frame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or SD with duration of at least 12 weeks or death due to cancer

Population: ITT

Arm	Measure	Value (NUMBER)
50 Milligram (mg) Sunitinib	Best Overall Response of PR or SD With Duration ≥12 Weeks	14 participants

Secondary

Circulating Endothelial Cells (CECs) and Circulating Endothelial Progenitor Cells (CEPs)

Blood samples for the assessment of CECs and circulating CEPs were planned to be obtained for subjects in Part 1 of the study, and for a subset of subjects in Part 2 of the study to complete the angiogenic profile of unresectable hepatocellular carcinoma, in addition to the soluble protein evaluation.

Time frame: Cycle 1 (Days 1, 14), Cycle 2 (Days 1, 28), Cycle 5 (Day 1)

Population: ITT. Blood samples for CECs and CEP cells were collected during the study, but evaluations of these samples were not performed.

Secondary

Clinical Benefit Response (CR, PR, or SD With Duration ≥12 Weeks)

Number of patients with Clinical Benefit Response: confirmed CR, confirmed PR, or SD for at least 12 weeks on study according to RECIST. CR=disappearance of all target lesions. PR= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions. SD=neither shrinkage for PR or increase for PD taking as reference smallest sum of longest dimensions since treatment start.

Time frame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or SD with duration of at least 12 weeks on study

Population: ITT

Arm	Measure	Value (NUMBER)
50 Milligram (mg) Sunitinib	Clinical Benefit Response (CR, PR, or SD With Duration ≥12 Weeks)	14 participants

95% CI: [22.5, 55.2]

Secondary

Ctrough of SU-012662 (Metabolite of Sunitinib)

Ctrough = the concentration prior to study drug administration.

Time frame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)

Population: PK

Arm	Measure	Group	Value (MEAN)	Dispersion
50 Milligram (mg) Sunitinib	Ctrough of SU-012662 (Metabolite of Sunitinib)	Cycle 2, Day 28 (n=19)	18.04 ng/mL	Standard Deviation 15.02
50 Milligram (mg) Sunitinib	Ctrough of SU-012662 (Metabolite of Sunitinib)	Cycle 3, Day 1 (n=16)	1.14 ng/mL	Standard Deviation 1.48
50 Milligram (mg) Sunitinib	Ctrough of SU-012662 (Metabolite of Sunitinib)	Cycle 3, Day 28 (n=16)	17.50 ng/mL	Standard Deviation 14.2
50 Milligram (mg) Sunitinib	Ctrough of SU-012662 (Metabolite of Sunitinib)	Cycle 5, Day 28 (n=12)	11.19 ng/mL	Standard Deviation 5.81
50 Milligram (mg) Sunitinib	Ctrough of SU-012662 (Metabolite of Sunitinib)	Cycle 1, Day 1 (n=37)	0.00 ng/mL	Standard Deviation 0
50 Milligram (mg) Sunitinib	Ctrough of SU-012662 (Metabolite of Sunitinib)	Cycle 1, Day 14 (n=32)	20.49 ng/mL	Standard Deviation 8.68
50 Milligram (mg) Sunitinib	Ctrough of SU-012662 (Metabolite of Sunitinib)	Cycle 1, Day 28 (n=29)	20.77 ng/mL	Standard Deviation 12.93
50 Milligram (mg) Sunitinib	Ctrough of SU-012662 (Metabolite of Sunitinib)	Cycle 2, Day 1 (n=25)	2.29 ng/mL	Standard Deviation 3.55

Secondary

Ctrough of Total Drug (Sunitinib + SU-012662)

Ctrough = the concentration prior to study drug administration.

Time frame: Cycle 1 (Days 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)

Population: PK

Arm	Measure	Group	Value (MEAN)	Dispersion
50 Milligram (mg) Sunitinib	Ctrough of Total Drug (Sunitinib + SU-012662)	Cycle 1, Day 14 (n=32)	95.54 ng/mL	Standard Deviation 41.72
50 Milligram (mg) Sunitinib	Ctrough of Total Drug (Sunitinib + SU-012662)	Cycle 1, Day 28 (n=28)	87.99 ng/mL	Standard Deviation 45.21
50 Milligram (mg) Sunitinib	Ctrough of Total Drug (Sunitinib + SU-012662)	Cycle 2, Day 1 (n=14)	9.92 ng/mL	Standard Deviation 11.52
50 Milligram (mg) Sunitinib	Ctrough of Total Drug (Sunitinib + SU-012662)	Cycle 2, Day 28 (n=19)	65.73 ng/mL	Standard Deviation 53.39
50 Milligram (mg) Sunitinib	Ctrough of Total Drug (Sunitinib + SU-012662)	Cycle 3, Day 1 (n=8)	4.49 ng/mL	Standard Deviation 2.98
50 Milligram (mg) Sunitinib	Ctrough of Total Drug (Sunitinib + SU-012662)	Cycle 3, Day 28 (n=16)	61.41 ng/mL	Standard Deviation 38.95
50 Milligram (mg) Sunitinib	Ctrough of Total Drug (Sunitinib + SU-012662)	Cycle 5, Day 28 (n=11)	47.11 ng/mL	Standard Deviation 17.84

Secondary

Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)

Data was dose-corrected to the starting dose (dose-corrected Ctrough = observed Ctrough x \[starting dose/actual dose\]).

Time frame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)

Population: PK

Arm	Measure	Group	Value (MEAN)	Dispersion
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)	Cycle 1, Day 1 (n=37)	0.00 ng/mL	Standard Deviation 0
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)	Cycle 1, Day 14 (n=29)	21.07 ng/mL	Standard Deviation 8.35
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)	Cycle 1, Day 28 (n=18)	24.20 ng/mL	Standard Deviation 10.32
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)	Cycle 2, Day 1 (n=12)	3.63 ng/mL	Standard Deviation 2.54
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)	Cycle 2, Day 28 (n=15)	22.86 ng/mL	Standard Deviation 14.93
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)	Cycle 3, Day 1 (n=7)	2.71 ng/mL	Standard Deviation 1
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)	Cycle 3, Day 28 (n=10)	24.67 ng/mL	Standard Deviation 17.05
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)	Cycle 5, Day 28 (n=10)	18.38 ng/mL	Standard Deviation 8.74

Secondary

Dose-Corrected Ctrough of Sunitinib

Data was dose-corrected to the starting dose (dose-corrected Ctrough = observed Ctrough x \[starting dose/actual dose\]).

Time frame: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)

Population: PK

Arm	Measure	Group	Value (MEAN)	Dispersion
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of Sunitinib	Cycle 1, Day 1 (n=37)	0.00 ng/mL	Standard Deviation 0
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of Sunitinib	Cycle 1, Day 14 (n=29)	78.52 ng/mL	Standard Deviation 34.97
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of Sunitinib	Cycle 1, Day 28 (n=18)	78.20 ng/mL	Standard Deviation 35.44
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of Sunitinib	Cycle 2, Day 1 (n=11)	6.55 ng/mL	Standard Deviation 9.08
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of Sunitinib	Cycle 2, Day 28 (n=15)	62.88 ng/mL	Standard Deviation 35.27
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of Sunitinib	Cycle 3, Day 1 (n=6)	3.01 ng/mL	Standard Deviation 1.67
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of Sunitinib	Cycle 3, Day 28 (n=10)	63.83 ng/mL	Standard Deviation 30.77
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of Sunitinib	Cycle 5, Day 28 (n=10)	58.50 ng/mL	Standard Deviation 30.39

Secondary

Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)

Data was dose-corrected to the starting dose (dose-corrected Ctrough = observed Ctrough x \[starting dose/actual dose\]).

Time frame: Cycle 1 (Days 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)

Population: PK

Arm	Measure	Group	Value (MEAN)	Dispersion
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)	Cycle 1, Day 14 (n=29)	99.59 ng/mL	Standard Deviation 40.43
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)	Cycle 1, Day 28 (n=18)	102.40 ng/mL	Standard Deviation 41.92
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)	Cycle 2, Day 1 (n=13)	8.89 ng/mL	Standard Deviation 11.08
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)	Cycle 2, Day 28 (n=15)	85.75 ng/mL	Standard Deviation 48.87
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)	Cycle 3, Day 1 (n=8)	4.63 ng/mL	Standard Deviation 2.85
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)	Cycle 3, Day 28 (n=10)	88.50 ng/mL	Standard Deviation 44.2
50 Milligram (mg) Sunitinib	Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)	Cycle 5, Day 28 (n=10)	76.87 ng/mL	Standard Deviation 35.89

Secondary

Duration of Objective Response (CR or PR)

Time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of disease progression or to death due to any cause. CR=disappearance of all target lesions. PR= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions.

Time frame: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death due to cancer

Population: From the Overall ITT population, only 1 subject had Objective Response for evaluation of duration of objective response.

Arm	Measure	Value (NUMBER)
50 Milligram (mg) Sunitinib	Duration of Objective Response (CR or PR)	32.4 Weeks

Secondary

Overall Survival (ITT Child Pugh Class A Subject Population)

Time from the date of first dose of study medication to the date of death due to any cause.

Time frame: From start of study treatment until death.

Population: ITT Child Pugh Class A (assessment of liver function) subject population

Arm	Measure	Value (MEDIAN)
50 Milligram (mg) Sunitinib	Overall Survival (ITT Child Pugh Class A Subject Population)	40.4 Weeks

Secondary

Overall Survival (Overall ITT)

Time from the date of first dose of study medication to the date of death due to any cause.

Time frame: From start of study treatment until death.

Population: ITT

Arm	Measure	Value (MEDIAN)
50 Milligram (mg) Sunitinib	Overall Survival (Overall ITT)	34.6 Weeks

Secondary

Plasma Concentration of Soluble KIT (sKIT)

Plasma concentrations of sKIT that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by ELISA analysis. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.