A Study of Sunitinib In Young Patients With Advanced Gastrointestinal Stromal Tumor

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01396148
• Collaborator: (none)
• Enrollment: 6
• Locations: 9
• Arms: 2
• Actual Duration (Months): 62
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Children and young adults with gastrointestinal stromal tumors (GIST) will be treated with sunitinib. The safety (including pharmacokinetics) and tolerability of sunitinib will be studied in these patients. In addition, tumor responses and overall survival will be assessed.

Condition or Disease	Intervention/Treatment	Phase
Gastrointestinal Stromal Tumors	Drug: sunitinib malate dose escalation; Drug: sunitinib malate	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Non-Randomized
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A PHASE I/II STUDY OF SUNITINIB IN YOUNG PATIENTS WITH ADVANCED GASTROINTESTINAL STROMAL TUMOR
• Actual Study Start Date: Jun 1, 2012
• Actual Primary Completion Date: Aug 1, 2017
• Actual Study Completion Date: Aug 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Children with GIST children ages 6yrs-<18yrs	Drug: sunitinib malate dose escalation; sunitinib starting dose will be 15mg/m^2 daily on a 4 weeks on/2 weeks off schedule (Schedule 4/2).
Experimental: Young adults with GIST young adults ages 18yrs-<21 yrs	Drug: sunitinib malate; sunitinib 50mg daily on Schedule 4/2

Outcome Measures

Primary Outcome Measures

1. Estimated Steady-State Maximum Plasma Concentration (Cmax,ss) of Sunitinib and Its Metabolite [pre-dose on Day 1, Day 12-18 and Day 25-29 of Cycle 1,2, 3 and 2, 4, 6, 8 hours post-dose on Day 1 Cycle 1]

   Estimated steady-state maximum plasma concentration (Cmax,ss) of Sunitinib and its metabolite SU012662. Summarized data for all time points was reported.

2. Estimated Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose AUC(0-24) of Sunitinib and Its Metabolite [pre-dose on Day 1, Day 12-18 and Day 25-29 of Cycle 1,2, 3 and 2, 4, 6, 8 hours post-dose on Day 1 Cycle 1]

   Estimated area under the plasma concentration versus time curve from time zero to 24 hours post dose (AUC24) of Sunitinib and its metabolite SU012662. Summarized data for all time points was reported.

3. Estimated Oral Clearance (CL/F) of Sunitinib and Its Metabolite [pre-dose on Day 1, Day 12-18 and Day 25-29 of Cycle 1,2, 3 and 2, 4, 6, 8 hours post-dose on Day 1 Cycle 1]

   SU012662 is the metabolite of Sunitinib. Oral clearance (CL/F) is a quantitative measure of the rate at which a drug substance is removed from the blood (CL) normalized by the oral bioavailability of the drug (F). Summarized data for all time points was reported.

4. Maximum Observed Plasma Concentration (Cmax) of Sunitinib and Its Metabolite [Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose]

   SU012662 is the metabolite of Sunitinib.

5. Time to Reach Maximum Observed Plasma Concentration (Tmax) for Sunitinib and Its Metabolite [Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose]

   SU012662 is the metabolite of Sunitinib.

6. Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours Post Dose AUC(0-8) for Sunitinib and Its Metabolite [Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose]

   AUC(0-8) was defined as area under the plasma concentration time-curve from time zero to 8 hours post dose. SU012662 is the metabolite of Sunitinib.

Secondary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline up to end of study (up to Cycle 18, each cycle was of 42 days)]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to end of study (up to Cycle 18) that were absent before treatment or that worsened relative to pretreatment state. AEs included both non-serious adverse events (AEs) and SAEs.

2. Number of Participants With Treatment-Emergent Adverse Events (AEs) Greater Than or Equal to (>=) Grade 3, Based on National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE), Version 4.0 [Baseline up to end of study (up to Cycle 18, each cycle was of 42 days)]

   An AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. As per NCI CTCAE, Grade 3 events =medically significant but not immediately life-threatening, unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment, Grade 4 events =participant to be in imminent danger of death. Grade 5 events =death. Treatment-emergent events are events between first dose of study drug and up to end of study (up to Cycle 18) that were absent before treatment or that worsened relative to pretreatment state. Number of participants with AEs of any of the Grade 3 or above (Grade 4, 5) were reported.

3. Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline up to end of study (up to Cycle 18, each cycle was of 42 days)]

   An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both non-serious adverse events (AEs) and SAEs.

4. Number of Participants With Clinically Significant Laboratory Abnormalities [Baseline up to end of study (up to Cycle 18, each cycle was of 42 days)]

   Criteria for clinically significant laboratory abnormalities: Hemoglobin (Hb), hematocrit: less than (<) 0.8*lower limit of normal (LLN), platelet: <75 or greater than (>) 700*10^3/millimeter (mm)^3*upper limit of normal (ULN), leukocyte: <2.5 or >17.5*10^3/mm^3*ULN; total bilirubin 1.5*ULN, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase: >3.0*ULN, total protein, albumin: <0.8*LLN or >1.2*ULN ;blood urea nitrogen, creatinine: >1.3*ULN, uric acid >1.2*ULN; sodium <0.95*LLN or >1.05*ULN, potassium, calcium: <0.9*LLN or >1.1*ULN, albumin, total protein <0.8*LLN or >1.2*ULN; glucose <0.6*LLN or >1.5*ULN, creatine kinase >2.0*ULN; urine (red blood cell, white blood cell >6/high power field).

5. Number of Participants With Objective Response [Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days)]

   Objective response in participants was defined as the number of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Confirmed response were those that persisted on repeat imaging study for at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and non-target). PR was defined as at least 30 percentage (%) decrease in the sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non-target lesions not increased or absent.

6. Duration of Response [Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days)]

   Duration of response was defined as time (in months) from the first documentation of objective tumor response (confirmed CR or PR) to the first documentation of disease progression or death due to any cause. Confirmed response were those that persisted on repeat imaging study for at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and non-target). PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non-target lesions not increased or absent. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

7. Progression-Free Survival [Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days)]

   Progression free survival was defined as time (in months) from date of enrollment to the first documentation of disease progression or to death (due to any cause), whichever occurred first. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

8. Overall Survival [Baseline until death or discontinuation from the study whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days)]

   Overall survival was defined as time (in months) from enrollment to the date of death due to any cause. Analysis was performed using Kaplan-Meier method.

9. Number of Participants With Adverse Events Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) for Pharmacokinetic (PK) Subgroups [Cycle 1 Day 28 up to Cycle 3 (each cycle 42 days)]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI CTCAE version 4.0, Grade1= asymptomatic or mild symptoms, Grade 2= Moderate;local or noninvasive intervention indicated; Grade 3 events =medically significant but not immediately life-threatening, unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment, Grade 4 events =participant to be in imminent danger of death. Grade 5 events =death. Participants with any of the Grade 1 to Grade 5 AEs were reported. The PK evaluable participants were divided into 2 PK subgroups on Day 28 of Cycle 1: those with total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) value less than (<) the median Ctrough value(lower exposure) and those with total drug (sunitinib + SU012662) Ctrough values greater than or equal to (>=) the median Ctrough value(higher exposure).

10. Pearson Correlation Coefficient Between Percent Change From Baseline in Laboratory Parameters With Total Drug (Sunitinib + SU012662) Concentration [Baseline, Day 28 of Cycle 1, Cycle 2 and Cycle 3 (each cycle was of 42 days)]

    Pearson correlation coefficient between percent change from baseline in laboratory parameters with total drug (Sunitinib + SU012662) concentration were calculated on Day 28 of Cycles 1, 2, and 3. Laboratory parameters included absolute neutrophil count, platelet count, lymphocyte count and hemoglobin.

11. Pearson Correlation Coefficient Between Percent Change From Baseline in Vital Sign Results With Total Drug (Sunitinib + SU012662) Concentration [Baseline, Day 28 of Cycle 1, Cycle 2 and Cycle 3 (each cycle was of 42 days)]

    Pearson correlation coefficient between percent change from baseline in vital sign results with total drug (Sunitinib + SU012662) concentration were calculated on Day 28 of Cycles 1, 2, and 3. Vital signs included systolic blood pressure and diastolic blood pressure.

12. Number of Participants With Stable Disease (SD), Partial Response (PR), Complete Response (CR) and Progressive Disease (PD) for PK Sub-groups [Baseline until disease progression or discontinuation from the study, or death, whichever occurred first(maximum duration: up to Cycle 18; each cycle was of 42 days)]

    SD:when there is no sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PR: as at least 30% decrease in the sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non-target lesions not increased or absent. CR: disappearance of all lesions (target and non-target). PD:at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Participants with SD, PR, CR and PD responses were assessed according to 2 PK subgroups created on Day 28 of Cycle 1: those with total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) value less than (<) the median Ctrough value(lower exposure) and those with total drug (sunitinib + SU012662) Ctrough values greater than or equal to (>=) the median Ctrough value(higher exposure).

13. Progression Free Survival for PK Subgroups [Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days)]

    Progression free survival was defined as time (in months) from date of enrollment to the first documentation of disease progression or to death (due to any cause), whichever occurred first. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The PK evaluable participants were assessed according to 2 PK subgroups created on Day 28 of Cycle 1: those with total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) value less than (<) the median Ctrough value(lower exposure) and those with total drug (sunitinib + SU012662) Ctrough values greater than or equal to (>=) the median Ctrough value(higher exposure).

14. Pearson Correlation Coefficient Between Progression Free Survival With Total Drug (Sunitinib + SU012662) Concentration [Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days]

    Pearson correlation coefficient between Progression Free Survival (PFS) with total drug (Sunitinib + SU012662) concentration at Day 28 of Cycle 1 was calculated. PFS was defined as time (in months) from date of enrolment to the first documentation of disease progression or to death (due to any cause), whichever occurred first. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

15. Estimated Sunitinib Plasma Concentration at Which 50% of the Maximum Effect (EC50) for Each Selected Efficacy Parameter (e.g., Sum of Largest Diameters for Target Tumors) Was Observed [Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose]

16. Estimated Sunitinib Plasma Concentration at Which 50% of the Maximum Effect (EC50) for Each Selected Safety Endpoint (e.g., Absolute Neutrophil Count) Was Observed [Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 20 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histological diagnosis of GIST.

• Patients must have demonstrated either disease progression or intolerance to imatinib mesylate, have non-mutant Stem Cell Factor Receptor gene (KIT) GIST, or cannot obtain imatinib in their country

• Measurable by Response Evaluation Criterion in Solid Tumors (RECIST) or evaluable disease.

Exclusion Criteria:

• Current treatment with another investigational agent.

• Prior sunitinib treatment.

• Prior therapy with known risk for cardiovascular complications.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles	Los Angeles	California	United States	90027
2	Children's Hospital Boston	Boston	Massachusetts	United States	02115
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
4	Fakultni nemocnice Brno	Brno		Czechia	613 00
5	FN Brno	Brno		Czechia	625 00
6	Masarykuv onkologicky ustav	Brno		Czechia	656 33
7	CHU de La Timone, Hopital enfants	Marseille cedex 5		France	13385
8	Hopital d'Enfants de la Timone	Marseille cedex 5		France	13385
9	Hopital de la Timone	Marseille cedex 5		France	13385

Sponsors and Collaborators

• Pfizer

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Jul 31, 2017
• Statistical Analysis Plan - Jul 15, 2011

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01396148
• Other Study ID Numbers: A6181196; 2011-002008-33
• First Posted: Jul 18, 2011
• Last Update Posted: Mar 27, 2019
• Last Verified: Mar 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Pfizer: Children and young adults with GIST; sunitinib malate; pharmacokinetics; tumor response; overall survival; tumor KIT mutation status
• Additional relevant MeSH terms: Gastrointestinal Stromal Tumors; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Period Title: Overall Study
STARTED	6
COMPLETED	5
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Overall Participants	6
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.3 (1.4)
Sex: Female, Male (Count of Participants)
Female	5 83.3%
Male	1 16.7%
Race/Ethnicity, Customized (participants) [Number]
White	5 83.3%
Asian	1 16.7%

Outcome Measures

1. Primary Outcome

Title	Estimated Steady-State Maximum Plasma Concentration (Cmax,ss) of Sunitinib and Its Metabolite
Description	Estimated steady-state maximum plasma concentration (Cmax,ss) of Sunitinib and its metabolite SU012662. Summarized data for all time points was reported.
Time Frame	pre-dose on Day 1, Day 12-18 and Day 25-29 of Cycle 1,2, 3 and 2, 4, 6, 8 hours post-dose on Day 1 Cycle 1

Outcome Measure Data

Analysis Population Description

The PK population included all treated participants with at least one PK observation.

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Measure Participants	6
Sunitinib	37.98 (12.91)
SU012662	14.55 (3.04)

2. Primary Outcome

Title	Estimated Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose AUC(0-24) of Sunitinib and Its Metabolite
Description	Estimated area under the plasma concentration versus time curve from time zero to 24 hours post dose (AUC24) of Sunitinib and its metabolite SU012662. Summarized data for all time points was reported.
Time Frame	pre-dose on Day 1, Day 12-18 and Day 25-29 of Cycle 1,2, 3 and 2, 4, 6, 8 hours post-dose on Day 1 Cycle 1

Outcome Measure Data

Analysis Population Description

The PK population included all treated participants with at least one PK observation.

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Measure Participants	6
Sunitinib	812.59 (273.37)
SU012662	336.78 (74.15)

3. Primary Outcome

Title	Estimated Oral Clearance (CL/F) of Sunitinib and Its Metabolite
Description	SU012662 is the metabolite of Sunitinib. Oral clearance (CL/F) is a quantitative measure of the rate at which a drug substance is removed from the blood (CL) normalized by the oral bioavailability of the drug (F). Summarized data for all time points was reported.
Time Frame	pre-dose on Day 1, Day 12-18 and Day 25-29 of Cycle 1,2, 3 and 2, 4, 6, 8 hours post-dose on Day 1 Cycle 1

Outcome Measure Data

Analysis Population Description

The PK population included all treated participants with at least one PK observation.

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Measure Participants	6
Sunitinib	26.37 (7.62)
SU012662	12.85 (3.11)

4. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Sunitinib and Its Metabolite
Description	SU012662 is the metabolite of Sunitinib.
Time Frame	Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose

Outcome Measure Data

Analysis Population Description

The PK population included all treated participants with at least one PK observation.

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Measure Participants	6
Sunitinib	17.58 (32)
SU012662	2.342 (18)

5. Primary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) for Sunitinib and Its Metabolite
Description	SU012662 is the metabolite of Sunitinib.
Time Frame	Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose

Outcome Measure Data

Analysis Population Description

The PK population included all treated participants with at least one PK observation.

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Measure Participants	6
Sunitinib	8
SU012662	8

6. Primary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours Post Dose AUC(0-8) for Sunitinib and Its Metabolite
Description	AUC(0-8) was defined as area under the plasma concentration time-curve from time zero to 8 hours post dose. SU012662 is the metabolite of Sunitinib.
Time Frame	Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose

Outcome Measure Data

Analysis Population Description

The PK population included all treated participants with at least one PK observation.

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Measure Participants	6
Sunitinib	77.49 (42)
SU012662	10.11 (37)

7. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to end of study (up to Cycle 18) that were absent before treatment or that worsened relative to pretreatment state. AEs included both non-serious adverse events (AEs) and SAEs.
Time Frame	Baseline up to end of study (up to Cycle 18, each cycle was of 42 days)

Outcome Measure Data

Analysis Population Description

The as-treated population included all enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Measure Participants	6
AEs	6 100%
SAEs	0 0%

8. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) Greater Than or Equal to (>=) Grade 3, Based on National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE), Version 4.0
Description	An AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. As per NCI CTCAE, Grade 3 events =medically significant but not immediately life-threatening, unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment, Grade 4 events =participant to be in imminent danger of death. Grade 5 events =death. Treatment-emergent events are events between first dose of study drug and up to end of study (up to Cycle 18) that were absent before treatment or that worsened relative to pretreatment state. Number of participants with AEs of any of the Grade 3 or above (Grade 4, 5) were reported.
Time Frame	Baseline up to end of study (up to Cycle 18, each cycle was of 42 days)

Outcome Measure Data

Analysis Population Description

The as-treated population included all enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Measure Participants	6
Number [participants]	5 83.3%

9. Secondary Outcome

Title	Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both non-serious adverse events (AEs) and SAEs.
Time Frame	Baseline up to end of study (up to Cycle 18, each cycle was of 42 days)

Outcome Measure Data

Analysis Population Description

The as-treated population included all enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Measure Participants	6
AEs	6 100%
SAEs	0 0%

10. Secondary Outcome

Title	Number of Participants With Clinically Significant Laboratory Abnormalities
Description	Criteria for clinically significant laboratory abnormalities: Hemoglobin (Hb), hematocrit: less than (<) 0.8*lower limit of normal (LLN), platelet: <75 or greater than (>) 700*10^3/millimeter (mm)^3*upper limit of normal (ULN), leukocyte: <2.5 or >17.5*10^3/mm^3*ULN; total bilirubin 1.5*ULN, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase: >3.0*ULN, total protein, albumin: <0.8*LLN or >1.2*ULN ;blood urea nitrogen, creatinine: >1.3*ULN, uric acid >1.2*ULN; sodium <0.95*LLN or >1.05*ULN, potassium, calcium: <0.9*LLN or >1.1*ULN, albumin, total protein <0.8*LLN or >1.2*ULN; glucose <0.6*LLN or >1.5*ULN, creatine kinase >2.0*ULN; urine (red blood cell, white blood cell >6/high power field).
Time Frame	Baseline up to end of study (up to Cycle 18, each cycle was of 42 days)

Outcome Measure Data

Analysis Population Description

The as-treated population included all enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Measure Participants	6
Number [participants]	0 0%

11. Secondary Outcome

Title	Number of Participants With Objective Response
Description	Objective response in participants was defined as the number of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Confirmed response were those that persisted on repeat imaging study for at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and non-target). PR was defined as at least 30 percentage (%) decrease in the sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non-target lesions not increased or absent.
Time Frame	Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days)

Outcome Measure Data

Analysis Population Description

The full analysis set included all enrolled participants regardless of what treatment, if any, was received.

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Measure Participants	6
Complete response	0 0%
Partial response	0 0%

12. Secondary Outcome

Title	Duration of Response
Description	Duration of response was defined as time (in months) from the first documentation of objective tumor response (confirmed CR or PR) to the first documentation of disease progression or death due to any cause. Confirmed response were those that persisted on repeat imaging study for at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and non-target). PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non-target lesions not increased or absent. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Time Frame	Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days)

Outcome Measure Data

Analysis Population Description

Analysis was performed on a subset of FAS which included participants who had a confirmed CR or PR. Since, none of the participants had confirmed CR or PR, hence duration of response was not analyzed.

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Measure Participants	0

13. Secondary Outcome

Title	Progression-Free Survival
Description	Progression free survival was defined as time (in months) from date of enrollment to the first documentation of disease progression or to death (due to any cause), whichever occurred first. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Time Frame	Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days)

Outcome Measure Data

Analysis Population Description

The full analysis set included all enrolled participants regardless of what treatment, if any, was received.

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Measure Participants	6
Median (95% Confidence Interval) [months]	5.8

14. Secondary Outcome

Title	Overall Survival
Description	Overall survival was defined as time (in months) from enrollment to the date of death due to any cause. Analysis was performed using Kaplan-Meier method.
Time Frame	Baseline until death or discontinuation from the study whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days)

Outcome Measure Data

Analysis Population Description

The full analysis set included all enrolled participants regardless of what treatment, if any, was received.

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Measure Participants	6
Median (95% Confidence Interval) [months]	NA

15. Secondary Outcome

Title	Number of Participants With Adverse Events Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) for Pharmacokinetic (PK) Subgroups
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI CTCAE version 4.0, Grade1= asymptomatic or mild symptoms, Grade 2= Moderate;local or noninvasive intervention indicated; Grade 3 events =medically significant but not immediately life-threatening, unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment, Grade 4 events =participant to be in imminent danger of death. Grade 5 events =death. Participants with any of the Grade 1 to Grade 5 AEs were reported. The PK evaluable participants were divided into 2 PK subgroups on Day 28 of Cycle 1: those with total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) value less than (<) the median Ctrough value(lower exposure) and those with total drug (sunitinib + SU012662) Ctrough values greater than or equal to (>=) the median Ctrough value(higher exposure).
Time Frame	Cycle 1 Day 28 up to Cycle 3 (each cycle 42 days)

Outcome Measure Data

Analysis Population Description

The PK subgroup analysis set included all treated participants with at least 1 PK observation.

Arm/Group Title	Sunitinib: Lower Exposure	Sunitinib: Higher Exposure
Arm/Group Description	Participants who received Sunitinib capsules orally at a dose based on BSA (minimum dose of 15 mg/m^2 up to a maximum dose of 30 mg/m^2 once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) and had total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) < the median Ctrough value	Participants who received Sunitinib capsules orally at a dose based on BSA (minimum dose of 15 mg/m^2 up to a maximum dose of 30 mg/m^2 once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) and had total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) >= the median Ctrough value
Measure Participants	3	3
Nausea	0 0%	2 NaN
Vomiting	0 0%	1 NaN
Diarrhoea	0 0%	2 NaN
Fatigue	0 0%	1 NaN
Palmar-Plantar Erythrodysaesthesia Syndrome	1 16.7%	0 NaN
Neutropenia	2 33.3%	1 NaN
Thrombocytopenia	1 16.7%	1 NaN
Lymphopenia	0 0%	0 NaN
Hypertension	0 0%	0 NaN
Anaemia	1 16.7%	0 NaN

16. Secondary Outcome

Title	Pearson Correlation Coefficient Between Percent Change From Baseline in Laboratory Parameters With Total Drug (Sunitinib + SU012662) Concentration
Description	Pearson correlation coefficient between percent change from baseline in laboratory parameters with total drug (Sunitinib + SU012662) concentration were calculated on Day 28 of Cycles 1, 2, and 3. Laboratory parameters included absolute neutrophil count, platelet count, lymphocyte count and hemoglobin.
Time Frame	Baseline, Day 28 of Cycle 1, Cycle 2 and Cycle 3 (each cycle was of 42 days)

Outcome Measure Data

Analysis Population Description

The PK population included all treated participants with at least one PK observation.

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Measure Participants	6
Absolute Neutrophil Count: Cycle 1 Day 28	-0.1870
Absolute Neutrophil Count: Cycle 2 Day 28	-0.5914
Absolute Neutrophil Count: Cycle 3 Day 28	-0.5536
Platelet Count: Cycle 1 Day 28	0.0329
Platelet Count: Cycle 2 Day 28	-0.6424
Platelet Count: Cycle 3 Day 28	-0.6604
Lymphocyte Count: Cycle 1 Day 28	0.1509
Lymphocyte Count: Cycle 2 Day 28	-0.4815
Lymphocyte Count: Cycle 3 Day 28	-0.2931
Hemoglobin: Cycle 1 Day 28	0.9107
Hemoglobin: Cycle 2 Day 28	0.4368
Hemoglobin: Cycle 3 Day 28	0.2095

17. Secondary Outcome

Title	Pearson Correlation Coefficient Between Percent Change From Baseline in Vital Sign Results With Total Drug (Sunitinib + SU012662) Concentration
Description	Pearson correlation coefficient between percent change from baseline in vital sign results with total drug (Sunitinib + SU012662) concentration were calculated on Day 28 of Cycles 1, 2, and 3. Vital signs included systolic blood pressure and diastolic blood pressure.
Time Frame	Baseline, Day 28 of Cycle 1, Cycle 2 and Cycle 3 (each cycle was of 42 days)

Outcome Measure Data

Analysis Population Description

The PK population included all treated participants with at least one PK observation.

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Measure Participants	6
Systolic Blood Pressure: Cycle 1 Day 28	-0.3730
Systolic Blood Pressure: Cycle 2 Day 28	-0.8146
Systolic Blood Pressure: Cycle 3 Day 28	0.2768
Diastolic Blood Pressure: Cycle 1 Day 28	0.6854
Diastolic Blood Pressure: Cycle 2 Day 28	-0.3638
Diastolic Blood Pressure: Cycle 3 Day 28	0.2634

18. Secondary Outcome

Title	Number of Participants With Stable Disease (SD), Partial Response (PR), Complete Response (CR) and Progressive Disease (PD) for PK Sub-groups
Description	SD:when there is no sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PR: as at least 30% decrease in the sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non-target lesions not increased or absent. CR: disappearance of all lesions (target and non-target). PD:at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Participants with SD, PR, CR and PD responses were assessed according to 2 PK subgroups created on Day 28 of Cycle 1: those with total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) value less than (<) the median Ctrough value(lower exposure) and those with total drug (sunitinib + SU012662) Ctrough values greater than or equal to (>=) the median Ctrough value(higher exposure).
Time Frame	Baseline until disease progression or discontinuation from the study, or death, whichever occurred first(maximum duration: up to Cycle 18; each cycle was of 42 days)

Outcome Measure Data

Analysis Population Description

The PK population included all treated participants with at least 1 PK observation.

Arm/Group Title	Sunitinib: Lower Exposure	Sunitinib: Higher Exposure
Arm/Group Description	Participants who received Sunitinib capsules orally at a dose based on BSA (minimum dose of 15 mg/m^2 up to a maximum dose of 30 mg/m^2 once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) and had total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) < the median Ctrough value	Participants who received Sunitinib capsules orally at a dose based on BSA (minimum dose of 15 mg/m^2 up to a maximum dose of 30 mg/m^2 once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) and had total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) >= the median Ctrough value
Measure Participants	3	3
Stable Disease	1 16.7%	2 NaN
Partial Response	0 0%	0 NaN
Complete Response	0 0%	0 NaN
Progressive Disease	2 33.3%	1 NaN

19. Secondary Outcome

Title	Progression Free Survival for PK Subgroups
Description	Progression free survival was defined as time (in months) from date of enrollment to the first documentation of disease progression or to death (due to any cause), whichever occurred first. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The PK evaluable participants were assessed according to 2 PK subgroups created on Day 28 of Cycle 1: those with total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) value less than (<) the median Ctrough value(lower exposure) and those with total drug (sunitinib + SU012662) Ctrough values greater than or equal to (>=) the median Ctrough value(higher exposure).
Time Frame	Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days)

Outcome Measure Data

Analysis Population Description

The PK population included all treated participants with at least one PK observation.

Arm/Group Title	Sunitinib: Lower Exposure	Sunitinib: Higher Exposure
Arm/Group Description	Participants who received Sunitinib capsules orally at a dose based on BSA (minimum dose of 15 mg/m^2 up to a maximum dose of 30 mg/m^2 once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) and had total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) < the median Ctrough value	Participants who received Sunitinib capsules orally at a dose based on BSA (minimum dose of 15 mg/m^2 up to a maximum dose of 30 mg/m^2 once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) and had total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) >= the median Ctrough value
Measure Participants	3	3
Median (95% Confidence Interval) [months]	2.6	9.0

20. Secondary Outcome

Title	Pearson Correlation Coefficient Between Progression Free Survival With Total Drug (Sunitinib + SU012662) Concentration
Description	Pearson correlation coefficient between Progression Free Survival (PFS) with total drug (Sunitinib + SU012662) concentration at Day 28 of Cycle 1 was calculated. PFS was defined as time (in months) from date of enrolment to the first documentation of disease progression or to death (due to any cause), whichever occurred first. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Time Frame	Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days

Outcome Measure Data

Analysis Population Description

The PK population included all treated participants with at least one PK observation.

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Measure Participants	6
Number [correlation coefficient]	0.5904

21. Secondary Outcome

Title	Estimated Sunitinib Plasma Concentration at Which 50% of the Maximum Effect (EC50) for Each Selected Efficacy Parameter (e.g., Sum of Largest Diameters for Target Tumors) Was Observed
Time Frame	Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose

Outcome Measure Data

Analysis Population Description

Due to low number of enrolled participants (n=6), there was insufficient data to perform any type of pharmacokinetic/pharmacodynamic modeling to obtain EC50 values, hence data is not reported.

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Measure Participants	0

22. Secondary Outcome

Title	Estimated Sunitinib Plasma Concentration at Which 50% of the Maximum Effect (EC50) for Each Selected Safety Endpoint (e.g., Absolute Neutrophil Count) Was Observed
Time Frame	Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose

Outcome Measure Data

Analysis Population Description

Due to low number of enrolled participants (n=6), there was insufficient data to perform any type of pharmacokinetic/pharmacodynamic modeling to obtain EC50 values, hence data is not reported.

Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
Measure Participants	0

Adverse Events

Time Frame	Baseline up to end of study (up to Cycle 18, each cycle was of 42 days)
Adverse Event Reporting Description	Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Arm/Group Title	Sunitinib
Arm/Group Description	Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met.
All Cause Mortality
	Sunitinib
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Serious Adverse Events
	Sunitinib
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	Sunitinib
	Affected / at Risk (%)	# Events
Total	6/6 (100%)
Blood and lymphatic system disorders
Anaemia	2/6 (33.3%)
Leukopenia	1/6 (16.7%)
Lymphopenia	1/6 (16.7%)
Neutropenia	3/6 (50%)
Thrombocytopenia	2/6 (33.3%)
Cardiac disorders
Palpitations	1/6 (16.7%)
Endocrine disorders
Hypothyroidism	1/6 (16.7%)
Eye disorders
Vision blurred	1/6 (16.7%)
Gastrointestinal disorders
Abdominal pain	1/6 (16.7%)
Constipation	1/6 (16.7%)
Diarrhoea	3/6 (50%)
Dyspepsia	2/6 (33.3%)
Impaired gastric emptying	1/6 (16.7%)
Intra-abdominal haemorrhage	1/6 (16.7%)
Lip discolouration	1/6 (16.7%)
Nausea	3/6 (50%)
Sensitivity of teeth	1/6 (16.7%)
Vomiting	1/6 (16.7%)
General disorders
Asthenia	1/6 (16.7%)
Chest pain	1/6 (16.7%)
Fatigue	1/6 (16.7%)
Hepatobiliary disorders
Hepatic haematoma	1/6 (16.7%)
Infections and infestations
Ear infection	1/6 (16.7%)
Folliculitis	1/6 (16.7%)
Herpes simplex	1/6 (16.7%)
Nasopharyngitis	1/6 (16.7%)
Otitis media	1/6 (16.7%)
Sinusitis	1/6 (16.7%)
Tooth infection	1/6 (16.7%)
Upper respiratory tract infection	1/6 (16.7%)
Viral infection	1/6 (16.7%)
Investigations
Alanine aminotransferase increased	1/6 (16.7%)
Amylase increased	1/6 (16.7%)
Aspartate aminotransferase increased	1/6 (16.7%)
Blood alkaline phosphatase	1/6 (16.7%)
Blood phosphorus increased	1/6 (16.7%)
Blood uric acid increased	1/6 (16.7%)
Eosinophil count decreased	1/6 (16.7%)
Lymphocyte count decreased	1/6 (16.7%)
Neutrophil count decreased	1/6 (16.7%)
Weight decreased	1/6 (16.7%)
White blood cell count decreased	3/6 (50%)
Metabolism and nutrition disorders
Decreased appetite	2/6 (33.3%)
Hyperglycaemia	1/6 (16.7%)
Hyperkalaemia	1/6 (16.7%)
Hypermagnesaemia	1/6 (16.7%)
Hypocalcaemia	1/6 (16.7%)
Hypoglycaemia	1/6 (16.7%)
Hypophosphataemia	1/6 (16.7%)
Musculoskeletal and connective tissue disorders
Back pain	2/6 (33.3%)
Muscle spasms	1/6 (16.7%)
Musculoskeletal stiffness	1/6 (16.7%)
Myalgia	1/6 (16.7%)
Neck pain	1/6 (16.7%)
Nervous system disorders
Headache	4/6 (66.7%)
Migraine	1/6 (16.7%)
Psychiatric disorders
Insomnia	1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/6 (16.7%)
Nasal congestion	1/6 (16.7%)
Skin and subcutaneous tissue disorders
Acne	1/6 (16.7%)
Alopecia	1/6 (16.7%)
Erythema	1/6 (16.7%)
Hair colour changes	1/6 (16.7%)
Palmar-plantar erythrodysaesthesia syndrome	1/6 (16.7%)
Pruritus	1/6 (16.7%)
Rash	1/6 (16.7%)

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 less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.