Trial Outcomes & Findings for A Study of Sunitinib In Young Patients With Advanced Gastrointestinal Stromal Tumor (NCT NCT01396148)

Last Updated: 2019-03-27

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

6 participants

Primary outcome timeframe

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

Results posted on

2019-03-27

Participant Flow

Participant milestones

Participant milestones
Measure	Sunitinib 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 Study STARTED	6
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Sunitinib 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 Study Patient Decision	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sunitinib n=6 Participants 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.
Age, Continuous	14.3 years STANDARD_DEVIATION 1.4 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Race/Ethnicity, Customized White	5 participants n=5 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants

PRIMARY outcome

Timeframe: 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

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

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

Outcome measures

Outcome measures
Measure	Sunitinib n=6 Participants 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.	Sunitinib: Higher Exposure 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
Estimated Steady-State Maximum Plasma Concentration (Cmax,ss) of Sunitinib and Its Metabolite Sunitinib	37.98 nanograms per milliliter (ng/mL) Standard Deviation 12.91	—
Estimated Steady-State Maximum Plasma Concentration (Cmax,ss) of Sunitinib and Its Metabolite SU012662	14.55 nanograms per milliliter (ng/mL) Standard Deviation 3.04	—

PRIMARY outcome

Timeframe: 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

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

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.

Outcome measures

Outcome measures
Measure	Sunitinib n=6 Participants 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.	Sunitinib: Higher Exposure 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
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 Sunitinib	812.59 nanogramhour per milliliter (nghr)/mL Standard Deviation 273.37	—
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 SU012662	336.78 nanogramhour per milliliter (nghr)/mL Standard Deviation 74.15	—

PRIMARY outcome

Timeframe: 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

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

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.

Outcome measures

Outcome measures
Measure	Sunitinib n=6 Participants 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.	Sunitinib: Higher Exposure 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
Estimated Oral Clearance (CL/F) of Sunitinib and Its Metabolite Sunitinib	26.37 Liters per hour (L/hr) Standard Deviation 7.62	—
Estimated Oral Clearance (CL/F) of Sunitinib and Its Metabolite SU012662	12.85 Liters per hour (L/hr) Standard Deviation 3.11	—

PRIMARY outcome

Timeframe: Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose

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

SU012662 is the metabolite of Sunitinib.

Outcome measures

Outcome measures
Measure	Sunitinib n=6 Participants 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.	Sunitinib: Higher Exposure 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
Maximum Observed Plasma Concentration (Cmax) of Sunitinib and Its Metabolite Sunitinib	17.58 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 32	—
Maximum Observed Plasma Concentration (Cmax) of Sunitinib and Its Metabolite SU012662	2.342 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 18	—

PRIMARY outcome

Timeframe: Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose

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

SU012662 is the metabolite of Sunitinib.

Outcome measures

Outcome measures
Measure	Sunitinib n=6 Participants 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.	Sunitinib: Higher Exposure 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
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Sunitinib and Its Metabolite Sunitinib	8 hours Interval 4.0 to 8.0	—
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Sunitinib and Its Metabolite SU012662	8 hours Interval 4.0 to 8.0	—

PRIMARY outcome

Timeframe: Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose

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

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.

Outcome measures

Outcome measures
Measure	Sunitinib n=6 Participants 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.	Sunitinib: Higher Exposure 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
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours Post Dose AUC(0-8) for Sunitinib and Its Metabolite Sunitinib	77.49 nanogramshour per milliliter (nghr)/mL Geometric Coefficient of Variation 42	—
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours Post Dose AUC(0-8) for Sunitinib and Its Metabolite SU012662	10.11 nanogramshour per milliliter (nghr)/mL Geometric Coefficient of Variation 37	—

SECONDARY outcome

Timeframe: Baseline up to end of study (up to Cycle 18, each cycle was of 42 days)

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

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.

Outcome measures

Outcome measures
Measure	Sunitinib n=6 Participants 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.	Sunitinib: Higher Exposure 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
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	0 participants	—
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	6 participants	—

SECONDARY outcome

Timeframe: Baseline up to end of study (up to Cycle 18, each cycle was of 42 days)

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

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.

Outcome measures

Outcome measures
Measure	Sunitinib n=6 Participants 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.	Sunitinib: Higher Exposure 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
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	5 participants	—

SECONDARY outcome

Timeframe: Baseline up to end of study (up to Cycle 18, each cycle was of 42 days)

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

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.

Outcome measures

Outcome measures
Measure	Sunitinib n=6 Participants 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.	Sunitinib: Higher Exposure 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
Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	6 participants	—
Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	0 participants	—

SECONDARY outcome

Timeframe: Baseline up to end of study (up to Cycle 18, each cycle was of 42 days)

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

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).

Outcome measures

Outcome measures
Measure	Sunitinib n=6 Participants 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.	Sunitinib: Higher Exposure 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
Number of Participants With Clinically Significant Laboratory Abnormalities	0 participants	—

SECONDARY outcome

Timeframe: 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)

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

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.

Outcome measures

Outcome measures
Measure	Sunitinib n=6 Participants 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.	Sunitinib: Higher Exposure 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
Number of Participants With Objective Response Complete response	0 participants	—
Number of Participants With Objective Response Partial response	0 participants	—

SECONDARY outcome

Timeframe: 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)

Population: 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.

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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)

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

Outcome measures

Outcome measures
Measure	Sunitinib n=6 Participants 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.	Sunitinib: Higher Exposure 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
Progression-Free Survival	5.8 months Interval 2.3 to The upper limit of the 95% CI was not estimable due to the small number of events.	—

SECONDARY outcome

Timeframe: Baseline until death or discontinuation from the study whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days)

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

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.

Outcome measures

Outcome measures
Measure	Sunitinib n=6 Participants 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.	Sunitinib: Higher Exposure 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
Overall Survival	NA months There were no deaths in study population, hence OS was not summarized using the Kaplan-Meier method.	—

SECONDARY outcome

Timeframe: Cycle 1 Day 28 up to Cycle 3 (each cycle 42 days)

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

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).

Outcome measures

Outcome measures
Measure	Sunitinib n=3 Participants 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.	Sunitinib: Higher Exposure n=3 Participants 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
Number of Participants With Adverse Events Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) for Pharmacokinetic (PK) Subgroups Nausea	0 participants	2 participants
Number of Participants With Adverse Events Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) for Pharmacokinetic (PK) Subgroups Vomiting	0 participants	1 participants
Number of Participants With Adverse Events Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) for Pharmacokinetic (PK) Subgroups Diarrhoea	0 participants	2 participants
Number of Participants With Adverse Events Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) for Pharmacokinetic (PK) Subgroups Fatigue	0 participants	1 participants
Number of Participants With Adverse Events Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) for Pharmacokinetic (PK) Subgroups Palmar-Plantar Erythrodysaesthesia Syndrome	1 participants	0 participants
Number of Participants With Adverse Events Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) for Pharmacokinetic (PK) Subgroups Neutropenia	2 participants	1 participants
Number of Participants With Adverse Events Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) for Pharmacokinetic (PK) Subgroups Thrombocytopenia	1 participants	1 participants
Number of Participants With Adverse Events Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) for Pharmacokinetic (PK) Subgroups Lymphopenia	0 participants	0 participants
Number of Participants With Adverse Events Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) for Pharmacokinetic (PK) Subgroups Hypertension	0 participants	0 participants
Number of Participants With Adverse Events Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) for Pharmacokinetic (PK) Subgroups Anaemia	1 participants	0 participants

SECONDARY outcome

Timeframe: Baseline, Day 28 of Cycle 1, Cycle 2 and Cycle 3 (each cycle was of 42 days)

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

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.

Outcome measures

Outcome measures
Measure	Sunitinib n=6 Participants 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.	Sunitinib: Higher Exposure 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
Pearson Correlation Coefficient Between Percent Change From Baseline in Laboratory Parameters With Total Drug (Sunitinib + SU012662) Concentration Absolute Neutrophil Count: Cycle 1 Day 28	-0.1870 correlation coefficient	—
Pearson Correlation Coefficient Between Percent Change From Baseline in Laboratory Parameters With Total Drug (Sunitinib + SU012662) Concentration Absolute Neutrophil Count: Cycle 2 Day 28	-0.5914 correlation coefficient	—
Pearson Correlation Coefficient Between Percent Change From Baseline in Laboratory Parameters With Total Drug (Sunitinib + SU012662) Concentration Absolute Neutrophil Count: Cycle 3 Day 28	-0.5536 correlation coefficient	—
Pearson Correlation Coefficient Between Percent Change From Baseline in Laboratory Parameters With Total Drug (Sunitinib + SU012662) Concentration Platelet Count: Cycle 1 Day 28	0.0329 correlation coefficient	—
Pearson Correlation Coefficient Between Percent Change From Baseline in Laboratory Parameters With Total Drug (Sunitinib + SU012662) Concentration Platelet Count: Cycle 2 Day 28	-0.6424 correlation coefficient	—
Pearson Correlation Coefficient Between Percent Change From Baseline in Laboratory Parameters With Total Drug (Sunitinib + SU012662) Concentration Platelet Count: Cycle 3 Day 28	-0.6604 correlation coefficient	—
Pearson Correlation Coefficient Between Percent Change From Baseline in Laboratory Parameters With Total Drug (Sunitinib + SU012662) Concentration Lymphocyte Count: Cycle 1 Day 28	0.1509 correlation coefficient	—
Pearson Correlation Coefficient Between Percent Change From Baseline in Laboratory Parameters With Total Drug (Sunitinib + SU012662) Concentration Lymphocyte Count: Cycle 2 Day 28	-0.4815 correlation coefficient	—
Pearson Correlation Coefficient Between Percent Change From Baseline in Laboratory Parameters With Total Drug (Sunitinib + SU012662) Concentration Lymphocyte Count: Cycle 3 Day 28	-0.2931 correlation coefficient	—
Pearson Correlation Coefficient Between Percent Change From Baseline in Laboratory Parameters With Total Drug (Sunitinib + SU012662) Concentration Hemoglobin: Cycle 1 Day 28	0.9107 correlation coefficient	—
Pearson Correlation Coefficient Between Percent Change From Baseline in Laboratory Parameters With Total Drug (Sunitinib + SU012662) Concentration Hemoglobin: Cycle 2 Day 28	0.4368 correlation coefficient	—
Pearson Correlation Coefficient Between Percent Change From Baseline in Laboratory Parameters With Total Drug (Sunitinib + SU012662) Concentration Hemoglobin: Cycle 3 Day 28	0.2095 correlation coefficient	—

SECONDARY outcome

Timeframe: Baseline, Day 28 of Cycle 1, Cycle 2 and Cycle 3 (each cycle was of 42 days)

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

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.

Outcome measures

Outcome measures
Measure	Sunitinib n=6 Participants 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.	Sunitinib: Higher Exposure 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
Pearson Correlation Coefficient Between Percent Change From Baseline in Vital Sign Results With Total Drug (Sunitinib + SU012662) Concentration Diastolic Blood Pressure: Cycle 2 Day 28	-0.3638 correlation coefficient	—
Pearson Correlation Coefficient Between Percent Change From Baseline in Vital Sign Results With Total Drug (Sunitinib + SU012662) Concentration Diastolic Blood Pressure: Cycle 3 Day 28	0.2634 correlation coefficient	—
Pearson Correlation Coefficient Between Percent Change From Baseline in Vital Sign Results With Total Drug (Sunitinib + SU012662) Concentration Systolic Blood Pressure: Cycle 1 Day 28	-0.3730 correlation coefficient	—
Pearson Correlation Coefficient Between Percent Change From Baseline in Vital Sign Results With Total Drug (Sunitinib + SU012662) Concentration Systolic Blood Pressure: Cycle 2 Day 28	-0.8146 correlation coefficient	—
Pearson Correlation Coefficient Between Percent Change From Baseline in Vital Sign Results With Total Drug (Sunitinib + SU012662) Concentration Systolic Blood Pressure: Cycle 3 Day 28	0.2768 correlation coefficient	—
Pearson Correlation Coefficient Between Percent Change From Baseline in Vital Sign Results With Total Drug (Sunitinib + SU012662) Concentration Diastolic Blood Pressure: Cycle 1 Day 28	0.6854 correlation coefficient	—

SECONDARY outcome

Timeframe: 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)

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

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).

Outcome measures

Outcome measures
Measure	Sunitinib n=3 Participants 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.	Sunitinib: Higher Exposure n=3 Participants 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
Number of Participants With Stable Disease (SD), Partial Response (PR), Complete Response (CR) and Progressive Disease (PD) for PK Sub-groups Stable Disease	1 participants	2 participants
Number of Participants With Stable Disease (SD), Partial Response (PR), Complete Response (CR) and Progressive Disease (PD) for PK Sub-groups Partial Response	0 participants	0 participants
Number of Participants With Stable Disease (SD), Partial Response (PR), Complete Response (CR) and Progressive Disease (PD) for PK Sub-groups Complete Response	0 participants	0 participants
Number of Participants With Stable Disease (SD), Partial Response (PR), Complete Response (CR) and Progressive Disease (PD) for PK Sub-groups Progressive Disease	2 participants	1 participants

SECONDARY outcome

Timeframe: 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)

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

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).

Outcome measures

Outcome measures
Measure	Sunitinib n=3 Participants 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.	Sunitinib: Higher Exposure n=3 Participants 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
Progression Free Survival for PK Subgroups	2.6 months Interval 2.4 to The upper limit of the 95% CI was not estimable due to the small number of events	9.0 months Interval 2.3 to The upper limit of the 95% CI was not estimable due to the small number of events

SECONDARY outcome

Timeframe: 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

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

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).

Outcome measures

Outcome measures
Measure	Sunitinib n=6 Participants 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.	Sunitinib: Higher Exposure 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
Pearson Correlation Coefficient Between Progression Free Survival With Total Drug (Sunitinib + SU012662) Concentration	0.5904 correlation coefficient	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose

Population: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose

Outcome measures

Outcome data not reported

Adverse Events

Sunitinib

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Sunitinib n=6 participants at risk 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.
Blood and lymphatic system disorders Anaemia	33.3% 2/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Blood and lymphatic system disorders Leukopenia	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Blood and lymphatic system disorders Lymphopenia	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Blood and lymphatic system disorders Neutropenia	50.0% 3/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Blood and lymphatic system disorders Thrombocytopenia	33.3% 2/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Cardiac disorders Palpitations	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Endocrine disorders Hypothyroidism	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Eye disorders Vision blurred	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Gastrointestinal disorders Abdominal pain	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Gastrointestinal disorders Constipation	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Gastrointestinal disorders Diarrhoea	50.0% 3/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Gastrointestinal disorders Dyspepsia	33.3% 2/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Gastrointestinal disorders Impaired gastric emptying	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Gastrointestinal disorders Intra-abdominal haemorrhage	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Gastrointestinal disorders Lip discolouration	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Gastrointestinal disorders Nausea	50.0% 3/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Gastrointestinal disorders Sensitivity of teeth	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Gastrointestinal disorders Vomiting	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
General disorders Asthenia	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
General disorders Chest pain	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
General disorders Fatigue	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Hepatobiliary disorders Hepatic haematoma	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Infections and infestations Ear infection	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Infections and infestations Folliculitis	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Infections and infestations Herpes simplex	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Infections and infestations Nasopharyngitis	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Infections and infestations Otitis media	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Infections and infestations Sinusitis	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Infections and infestations Tooth infection	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Infections and infestations Upper respiratory tract infection	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Infections and infestations Viral infection	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Investigations Alanine aminotransferase increased	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Investigations Amylase increased	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Investigations Aspartate aminotransferase increased	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Investigations Blood alkaline phosphatase	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Investigations Blood phosphorus increased	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Investigations Blood uric acid increased	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Investigations Eosinophil count decreased	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Investigations Lymphocyte count decreased	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Investigations Neutrophil count decreased	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Investigations Weight decreased	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Investigations White blood cell count decreased	50.0% 3/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Metabolism and nutrition disorders Decreased appetite	33.3% 2/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Metabolism and nutrition disorders Hyperglycaemia	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Metabolism and nutrition disorders Hyperkalaemia	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Metabolism and nutrition disorders Hypermagnesaemia	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Metabolism and nutrition disorders Hypocalcaemia	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Metabolism and nutrition disorders Hypoglycaemia	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Metabolism and nutrition disorders Hypophosphataemia	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Musculoskeletal and connective tissue disorders Back pain	33.3% 2/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Musculoskeletal and connective tissue disorders Muscle spasms	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Musculoskeletal and connective tissue disorders Myalgia	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Musculoskeletal and connective tissue disorders Neck pain	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Nervous system disorders Headache	66.7% 4/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Nervous system disorders Migraine	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Psychiatric disorders Insomnia	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Respiratory, thoracic and mediastinal disorders Epistaxis	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Respiratory, thoracic and mediastinal disorders Nasal congestion	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Skin and subcutaneous tissue disorders Acne	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Skin and subcutaneous tissue disorders Alopecia	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Skin and subcutaneous tissue disorders Erythema	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Skin and subcutaneous tissue disorders Hair colour changes	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Skin and subcutaneous tissue disorders Pruritus	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.
Skin and subcutaneous tissue disorders Rash	16.7% 1/6 • Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) 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.

Additional Information

Pfizer ClinicalTrials.gov Call Center

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Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER