Trial Outcomes & Findings for An International Phase 2 Study Of SU011248 In Patients With Inoperable Liver Cancer (NCT NCT00247676)
NCT ID: NCT00247676
Last Updated: 2010-02-18
Results Overview
Number of subjects with best overall response. Complete response (CR)=disappearance of all target lesions. Partial Response (PR)= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions. Progressive disease (PD)= ≥ 20% increase in sum of longest dimensions of lesions taking as a reference smallest sum of the longest dimensions since treatment start, or the appearance of ≥ 1 new lesion. Stable disease (SD)=neither shrinkage for PR or increase for PD taking as reference smallest sum of longest dimensions since treatment start.
COMPLETED
PHASE2
37 participants
From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter
2010-02-18
Participant Flow
This study was designed using a Simon 2-stage design with the objective response rate as the primary efficacy endpoint. Enrollment was halted after the first stage because the minimum number of responders by Response Evaluation Criteria in Solid Tumors (RECIST) needed to continue into Stage 2 was not reached.
Participant milestones
| Measure |
50 Milligram (mg) Sunitinib
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Overall Study
STARTED
|
37
|
|
Overall Study
COMPLETED
|
1
|
|
Overall Study
NOT COMPLETED
|
36
|
Reasons for withdrawal
| Measure |
50 Milligram (mg) Sunitinib
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Overall Study
Death
|
5
|
|
Overall Study
Adverse Event
|
11
|
|
Overall Study
Lack of Efficacy
|
15
|
|
Overall Study
Other
|
3
|
|
Overall Study
Withdrawal by Subject
|
2
|
Baseline Characteristics
An International Phase 2 Study Of SU011248 In Patients With Inoperable Liver Cancer
Baseline characteristics by cohort
| Measure |
50 Milligram (mg) Sunitinib
n=37 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Age Continuous
|
59.0 years
STANDARD_DEVIATION 12.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafterPopulation: Intent-to-treat (ITT) population includes all patients enrolled in the study that received at least 1 dose of study medication.
Number of subjects with best overall response. Complete response (CR)=disappearance of all target lesions. Partial Response (PR)= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions. Progressive disease (PD)= ≥ 20% increase in sum of longest dimensions of lesions taking as a reference smallest sum of the longest dimensions since treatment start, or the appearance of ≥ 1 new lesion. Stable disease (SD)=neither shrinkage for PR or increase for PD taking as reference smallest sum of longest dimensions since treatment start.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=37 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Best Overall Response
CR
|
0 participants
|
|
Best Overall Response
PR
|
1 participants
|
|
Best Overall Response
SD
|
15 participants
|
|
Best Overall Response
Progressive Disease
|
11 participants
|
|
Best Overall Response
Not Evaluable
|
7 participants
|
|
Best Overall Response
Missing
|
3 participants
|
PRIMARY outcome
Timeframe: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafterPopulation: ITT
Number of patients with objective response: confirmed CR or confirmed PR according to RECIST. CR was defined as the disappearance of all target lesions. A PR was defined as a ≥30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. To be assigned a status of PR or CR, changes in tumor measurements in patients with responding tumors had to have been confirmed by repeat studies that were performed ≥ 4 weeks after the criteria for response were first met.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=37 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Objective Response (CR or PR)
|
1 participants
|
SECONDARY outcome
Timeframe: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death due to cancerPopulation: From the Overall ITT population, only 1 subject had Objective Response for evaluation of duration of objective response.
Time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of disease progression or to death due to any cause. CR=disappearance of all target lesions. PR= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=1 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Duration of Objective Response (CR or PR)
|
32.4 Weeks
|
SECONDARY outcome
Timeframe: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or SD with duration of at least 12 weeks on studyPopulation: ITT
Number of patients with Clinical Benefit Response: confirmed CR, confirmed PR, or SD for at least 12 weeks on study according to RECIST. CR=disappearance of all target lesions. PR= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions. SD=neither shrinkage for PR or increase for PD taking as reference smallest sum of longest dimensions since treatment start.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=37 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Clinical Benefit Response (CR, PR, or SD With Duration ≥12 Weeks)
|
14 participants
|
SECONDARY outcome
Timeframe: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or SD with duration of at least 12 weeks or death due to cancerPopulation: ITT
Number of patients with best overall response of PR or SD with duration ≥ 12 weeks. Best overall response was defined as the time from the first documentation of tumor response that was subsequently confirmed to the first documentation of disease progression or to death due to any cause. CR=disappearance of all target lesions. PR= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions. SD=neither shrinkage for PR or increase for PD taking as reference smallest sum of longest dimensions since treatment start.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=37 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Best Overall Response of PR or SD With Duration ≥12 Weeks
|
14 participants
|
SECONDARY outcome
Timeframe: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or deathPopulation: ITT
Time from start of study treatment to first documentation of objective tumor progression, or to death due to any cause.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=37 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Progression-Free Survival (Overall ITT)
|
16.1 Weeks
Interval 8.0 to 28.0
|
SECONDARY outcome
Timeframe: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or deathPopulation: ITT Child Pugh Class A (assessment of liver function) subject population = subjects enrolled in the study with Child-Pugh Class A that received at least 1 dose of study medication.
Time from start of study treatment to first documentation of objective tumor progression, or to death due to any cause.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=31 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Progression-Free Survival (ITT Child Pugh Class A Subject Population)
|
21.0 Weeks
Interval 8.1 to 32.4
|
SECONDARY outcome
Timeframe: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafterPopulation: ITT
Time from the start of study treatment to the first documentation of objective tumor progression.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=37 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Time to Tumor Progression (Overall ITT)
|
23.00 Weeks
Interval 11.71 to 34.14
|
SECONDARY outcome
Timeframe: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafterPopulation: ITT Child Pugh Class A (assessment of liver function) subject population
Time from the start of study treatment to the first documentation of objective tumor progression.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=31 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Time to Tumor Progression (ITT Child Pugh Class A Subject Population)
|
23.00 Weeks
Interval 16.14 to 34.14
|
SECONDARY outcome
Timeframe: From start of study treatment until death.Population: ITT
Time from the date of first dose of study medication to the date of death due to any cause.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=37 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Overall Survival (Overall ITT)
|
34.6 Weeks
Interval 19.0 to 57.0
|
SECONDARY outcome
Timeframe: From start of study treatment until death.Population: ITT Child Pugh Class A (assessment of liver function) subject population
Time from the date of first dose of study medication to the date of death due to any cause.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=31 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Overall Survival (ITT Child Pugh Class A Subject Population)
|
40.4 Weeks
Interval 23.4 to 65.1
|
SECONDARY outcome
Timeframe: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter up until 1 year.Population: ITT
Probability of survival 1 year after the first dose of study treatment.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=37 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
1-Year Survival Probability
|
0.324 Probability
|
SECONDARY outcome
Timeframe: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)Population: Pharmacokinetic (PK) = All subjects enrolled in the study who at least 1 PK sample collected.
Ctrough = the concentration prior to study drug administration.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=37 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Trough Plasma Concentrations (Ctrough) of Sunitinib
Cycle 1, Day 1 (n=37)
|
0.00 nanograms (ng)/milliliter (mL)
Standard Deviation 0.00
|
|
Trough Plasma Concentrations (Ctrough) of Sunitinib
Cycle 1, Day 14 (n=32)
|
75.05 nanograms (ng)/milliliter (mL)
Standard Deviation 35.74
|
|
Trough Plasma Concentrations (Ctrough) of Sunitinib
Cycle 1, Day 28 (n=29)
|
64.19 nanograms (ng)/milliliter (mL)
Standard Deviation 38.36
|
|
Trough Plasma Concentrations (Ctrough) of Sunitinib
Cycle 2, Day 1 (n=25)
|
3.27 nanograms (ng)/milliliter (mL)
Standard Deviation 6.87
|
|
Trough Plasma Concentrations (Ctrough) of Sunitinib
Cycle 2, Day 28 (n=19)
|
47.68 nanograms (ng)/milliliter (mL)
Standard Deviation 39.27
|
|
Trough Plasma Concentrations (Ctrough) of Sunitinib
Cycle 3, Day 1 (n=16)
|
1.11 nanograms (ng)/milliliter (mL)
Standard Deviation 1.78
|
|
Trough Plasma Concentrations (Ctrough) of Sunitinib
Cycle 3, Day 28 (n=16)
|
43.92 nanograms (ng)/milliliter (mL)
Standard Deviation 26.85
|
|
Trough Plasma Concentrations (Ctrough) of Sunitinib
Cycle 5, Day 28 (n=12)
|
31.99 nanograms (ng)/milliliter (mL)
Standard Deviation 18.20
|
SECONDARY outcome
Timeframe: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)Population: PK
Ctrough = the concentration prior to study drug administration.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=37 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Ctrough of SU-012662 (Metabolite of Sunitinib)
Cycle 1, Day 1 (n=37)
|
0.00 ng/mL
Standard Deviation 0.00
|
|
Ctrough of SU-012662 (Metabolite of Sunitinib)
Cycle 1, Day 14 (n=32)
|
20.49 ng/mL
Standard Deviation 8.68
|
|
Ctrough of SU-012662 (Metabolite of Sunitinib)
Cycle 1, Day 28 (n=29)
|
20.77 ng/mL
Standard Deviation 12.93
|
|
Ctrough of SU-012662 (Metabolite of Sunitinib)
Cycle 2, Day 1 (n=25)
|
2.29 ng/mL
Standard Deviation 3.55
|
|
Ctrough of SU-012662 (Metabolite of Sunitinib)
Cycle 2, Day 28 (n=19)
|
18.04 ng/mL
Standard Deviation 15.02
|
|
Ctrough of SU-012662 (Metabolite of Sunitinib)
Cycle 3, Day 1 (n=16)
|
1.14 ng/mL
Standard Deviation 1.48
|
|
Ctrough of SU-012662 (Metabolite of Sunitinib)
Cycle 3, Day 28 (n=16)
|
17.50 ng/mL
Standard Deviation 14.20
|
|
Ctrough of SU-012662 (Metabolite of Sunitinib)
Cycle 5, Day 28 (n=12)
|
11.19 ng/mL
Standard Deviation 5.81
|
SECONDARY outcome
Timeframe: Cycle 1 (Days 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)Population: PK
Ctrough = the concentration prior to study drug administration.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=32 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Ctrough of Total Drug (Sunitinib + SU-012662)
Cycle 1, Day 14 (n=32)
|
95.54 ng/mL
Standard Deviation 41.72
|
|
Ctrough of Total Drug (Sunitinib + SU-012662)
Cycle 1, Day 28 (n=28)
|
87.99 ng/mL
Standard Deviation 45.21
|
|
Ctrough of Total Drug (Sunitinib + SU-012662)
Cycle 2, Day 1 (n=14)
|
9.92 ng/mL
Standard Deviation 11.52
|
|
Ctrough of Total Drug (Sunitinib + SU-012662)
Cycle 2, Day 28 (n=19)
|
65.73 ng/mL
Standard Deviation 53.39
|
|
Ctrough of Total Drug (Sunitinib + SU-012662)
Cycle 3, Day 1 (n=8)
|
4.49 ng/mL
Standard Deviation 2.98
|
|
Ctrough of Total Drug (Sunitinib + SU-012662)
Cycle 3, Day 28 (n=16)
|
61.41 ng/mL
Standard Deviation 38.95
|
|
Ctrough of Total Drug (Sunitinib + SU-012662)
Cycle 5, Day 28 (n=11)
|
47.11 ng/mL
Standard Deviation 17.84
|
SECONDARY outcome
Timeframe: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)Population: PK
Data was dose-corrected to the starting dose (dose-corrected Ctrough = observed Ctrough x \[starting dose/actual dose\]).
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=37 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Dose-Corrected Ctrough of Sunitinib
Cycle 1, Day 1 (n=37)
|
0.00 ng/mL
Standard Deviation 0.00
|
|
Dose-Corrected Ctrough of Sunitinib
Cycle 1, Day 14 (n=29)
|
78.52 ng/mL
Standard Deviation 34.97
|
|
Dose-Corrected Ctrough of Sunitinib
Cycle 1, Day 28 (n=18)
|
78.20 ng/mL
Standard Deviation 35.44
|
|
Dose-Corrected Ctrough of Sunitinib
Cycle 2, Day 1 (n=11)
|
6.55 ng/mL
Standard Deviation 9.08
|
|
Dose-Corrected Ctrough of Sunitinib
Cycle 2, Day 28 (n=15)
|
62.88 ng/mL
Standard Deviation 35.27
|
|
Dose-Corrected Ctrough of Sunitinib
Cycle 3, Day 1 (n=6)
|
3.01 ng/mL
Standard Deviation 1.67
|
|
Dose-Corrected Ctrough of Sunitinib
Cycle 3, Day 28 (n=10)
|
63.83 ng/mL
Standard Deviation 30.77
|
|
Dose-Corrected Ctrough of Sunitinib
Cycle 5, Day 28 (n=10)
|
58.50 ng/mL
Standard Deviation 30.39
|
SECONDARY outcome
Timeframe: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)Population: PK
Data was dose-corrected to the starting dose (dose-corrected Ctrough = observed Ctrough x \[starting dose/actual dose\]).
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=37 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)
Cycle 2, Day 28 (n=15)
|
22.86 ng/mL
Standard Deviation 14.93
|
|
Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)
Cycle 1, Day 1 (n=37)
|
0.00 ng/mL
Standard Deviation 0.00
|
|
Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)
Cycle 1, Day 14 (n=29)
|
21.07 ng/mL
Standard Deviation 8.35
|
|
Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)
Cycle 1, Day 28 (n=18)
|
24.20 ng/mL
Standard Deviation 10.32
|
|
Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)
Cycle 2, Day 1 (n=12)
|
3.63 ng/mL
Standard Deviation 2.54
|
|
Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)
Cycle 3, Day 1 (n=7)
|
2.71 ng/mL
Standard Deviation 1.00
|
|
Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)
Cycle 3, Day 28 (n=10)
|
24.67 ng/mL
Standard Deviation 17.05
|
|
Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)
Cycle 5, Day 28 (n=10)
|
18.38 ng/mL
Standard Deviation 8.74
|
SECONDARY outcome
Timeframe: Cycle 1 (Days 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28)Population: PK
Data was dose-corrected to the starting dose (dose-corrected Ctrough = observed Ctrough x \[starting dose/actual dose\]).
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=37 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)
Cycle 1, Day 14 (n=29)
|
99.59 ng/mL
Standard Deviation 40.43
|
|
Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)
Cycle 1, Day 28 (n=18)
|
102.40 ng/mL
Standard Deviation 41.92
|
|
Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)
Cycle 2, Day 1 (n=13)
|
8.89 ng/mL
Standard Deviation 11.08
|
|
Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)
Cycle 2, Day 28 (n=15)
|
85.75 ng/mL
Standard Deviation 48.87
|
|
Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)
Cycle 3, Day 1 (n=8)
|
4.63 ng/mL
Standard Deviation 2.85
|
|
Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)
Cycle 3, Day 28 (n=10)
|
88.50 ng/mL
Standard Deviation 44.20
|
|
Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)
Cycle 5, Day 28 (n=10)
|
76.87 ng/mL
Standard Deviation 35.89
|
SECONDARY outcome
Timeframe: Cycle 1 (Days 1, 14), Cycle 2 (Days 1, 28), Cycle 5 (Day 1)Population: ITT. Blood samples for CECs and CEP cells were collected during the study, but evaluations of these samples were not performed.
Blood samples for the assessment of CECs and circulating CEPs were planned to be obtained for subjects in Part 1 of the study, and for a subset of subjects in Part 2 of the study to complete the angiogenic profile of unresectable hepatocellular carcinoma, in addition to the soluble protein evaluation.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 28 of Cycle 1 (optional)Population: ITT. Tumor biopsy results were collected optionally in 5 subjects; however, no evaluations were performed.
Provision of previously collected tumor paraffin blocks (or at least 5-10 4-micron slides prepared from the paraffin block) for correlative laboratory analysis was optional. For all subjects showing OR on study, it was highly recommended to provide previously collected paraffin blocks (or at least 5-10 4-micron slides prepared from the paraffin block). These samples were to be analyzed for markers that may be associated with tumor proliferation or angiogenesis.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28)Population: ITT
Plasma concentrations of VEGF that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by e nzyme-linked immunosorbent assay (ELISA). Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=37 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Plasma Concentration of Vascular Endothelial Growth Factor (VEGF)
Cycle 1, Day 1 (n=37)
|
54.9 picograms (pg)/mL
Interval 20.2 to 466.3
|
|
Plasma Concentration of Vascular Endothelial Growth Factor (VEGF)
Cycle 1, Day 14 (n=33)
|
210.7 picograms (pg)/mL
Interval 71.4 to 2301.8
|
|
Plasma Concentration of Vascular Endothelial Growth Factor (VEGF)
Cycle 1, Day 28 (n=28)
|
182.9 picograms (pg)/mL
Interval 43.6 to 973.0
|
|
Plasma Concentration of Vascular Endothelial Growth Factor (VEGF)
Cycle 2, Day 1 (n=25)
|
81.3 picograms (pg)/mL
Interval 27.4 to 328.3
|
|
Plasma Concentration of Vascular Endothelial Growth Factor (VEGF)
Cycle 2, Day 28 (n=19)
|
234.7 picograms (pg)/mL
Interval 51.1 to 1717.6
|
|
Plasma Concentration of Vascular Endothelial Growth Factor (VEGF)
Cycle 5, Day 28 (n=12)
|
157.8 picograms (pg)/mL
Interval 91.0 to 2666.9
|
SECONDARY outcome
Timeframe: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28)Population: ITT
Plasma concentrations of VEGF-C that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by ELISA. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=37 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Plasma Concentration of VEGF-C
Cycle 1, Day 1 (n=37)
|
822.2 pg/mL
Interval 334.5 to 3216.5
|
|
Plasma Concentration of VEGF-C
Cycle 1, Day 14 (n=33)
|
731.7 pg/mL
Interval 394.6 to 3540.5
|
|
Plasma Concentration of VEGF-C
Cycle 1, Day 28 (n=28)
|
693.1 pg/mL
Interval 336.4 to 1862.3
|
|
Plasma Concentration of VEGF-C
Cycle 2, Day 1 (n=25)
|
733.8 pg/mL
Interval 457.9 to 1390.3
|
|
Plasma Concentration of VEGF-C
Cycle 2, Day 28 (n=19)
|
601.6 pg/mL
Interval 339.9 to 1565.4
|
|
Plasma Concentration of VEGF-C
Cycle 5, Day 28 (n=12)
|
802.7 pg/mL
Interval 441.9 to 2268.7
|
SECONDARY outcome
Timeframe: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28)Population: ITT
Plasma concentrations of sVEGFR-2 that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by ELISA. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline). Samples below the limit of quantitation and samples with insufficient volume available were excluded.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=37 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Plasma Concentration of Soluble VEGF Receptor-2 (sVEGFR-2)
Cycle 1, Day 1 (n=37)
|
7068.5 pg/mL
Interval 4572.5 to 13667.5
|
|
Plasma Concentration of Soluble VEGF Receptor-2 (sVEGFR-2)
Cycle 1, Day 14 (n=33)
|
3824.5 pg/mL
Interval 2044.5 to 9404.0
|
|
Plasma Concentration of Soluble VEGF Receptor-2 (sVEGFR-2)
Cycle 1, Day 28 (n=28)
|
3105.8 pg/mL
Interval 1566.0 to 9391.5
|
|
Plasma Concentration of Soluble VEGF Receptor-2 (sVEGFR-2)
Cycle 2, Day 1 (n=25)
|
6121.5 pg/mL
Interval 2604.0 to 12471.0
|
|
Plasma Concentration of Soluble VEGF Receptor-2 (sVEGFR-2)
Cycle 2, Day 28 (n=19)
|
3542 pg/mL
Interval 2148.0 to 9416.5
|
|
Plasma Concentration of Soluble VEGF Receptor-2 (sVEGFR-2)
Cycle 5, Day 28 (n=12)
|
4408.5 pg/mL
Interval 1742.0 to 10612.0
|
SECONDARY outcome
Timeframe: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28)Population: ITT
Plasma concentrations of sVEGFR-3 that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by ELISA. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=37 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3)
Cycle 1, Day 1 (n=37)
|
48700 pg/mL
Interval 12420.0 to 119300.0
|
|
Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3)
Cycle 1, Day 14 (n=33)
|
25300 pg/mL
Interval 5760.0 to 79000.0
|
|
Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3)
Cycle 1, Day 28 (n=28)
|
11075 pg/mL
Interval 3060.0 to 54050.0
|
|
Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3)
Cycle 2, Day 1 (n=25)
|
44100 pg/mL
Interval 6820.0 to 95900.0
|
|
Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3)
Cycle 2, Day 28 (n=19)
|
11450 pg/mL
Interval 4920.0 to 44870.0
|
|
Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3)
Cycle 5, Day 28 (n=12)
|
12430 pg/mL
Interval 6230.0 to 72300.0
|
SECONDARY outcome
Timeframe: Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28)Population: ITT
Plasma concentrations of sKIT that may be associated with tumor proliferation or angiogenesis were collected from a subset of subjects and analyzed by ELISA analysis. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio to Baseline = plasma concentration of soluble protein at timepoint / concentration of soluble protein at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
Outcome measures
| Measure |
50 Milligram (mg) Sunitinib
n=37 Participants
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Plasma Concentration of Soluble KIT (sKIT)
Cycle 1, Day 1 (n=37)
|
41960 pg/mL
Interval 17560.0 to 85345.0
|
|
Plasma Concentration of Soluble KIT (sKIT)
Cycle 1, Day 14 (n=33)
|
32680 pg/mL
Interval 14005.0 to 57840.0
|
|
Plasma Concentration of Soluble KIT (sKIT)
Cycle 1, Day 28 (n=28)
|
22910 pg/mL
Interval 12710.0 to 37400.0
|
|
Plasma Concentration of Soluble KIT (sKIT)
Cycle 2, Day 1 (n=25)
|
21615 pg/mL
Interval 9520.0 to 41855.0
|
|
Plasma Concentration of Soluble KIT (sKIT)
Cycle 2, Day 28 (n=19)
|
18125 pg/mL
Interval 10995.0 to 35940.0
|
|
Plasma Concentration of Soluble KIT (sKIT)
Cycle 5, Day 28 (n=12)
|
18420 pg/mL
Interval 8265.0 to 29115.0
|
Adverse Events
50 Milligram (mg) Sunitinib
Serious adverse events
| Measure |
50 Milligram (mg) Sunitinib
n=37 participants at risk
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
16.2%
6/37
|
|
Blood and lymphatic system disorders
Leukopenia
|
2.7%
1/37
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.4%
2/37
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
16.2%
6/37
|
|
Cardiac disorders
Myocardial infarction
|
2.7%
1/37
|
|
Eye disorders
Cataract
|
2.7%
1/37
|
|
Gastrointestinal disorders
Abdominal pain
|
2.7%
1/37
|
|
Gastrointestinal disorders
Ascites
|
2.7%
1/37
|
|
Gastrointestinal disorders
Gastritis
|
2.7%
1/37
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
8.1%
3/37
|
|
Gastrointestinal disorders
Gingival bleeding
|
2.7%
1/37
|
|
Gastrointestinal disorders
Haematemesis
|
2.7%
1/37
|
|
Gastrointestinal disorders
Melaena
|
5.4%
2/37
|
|
Gastrointestinal disorders
Mouth haemorrhage
|
2.7%
1/37
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
10.8%
4/37
|
|
Gastrointestinal disorders
Peritoneal effusion
|
2.7%
1/37
|
|
Gastrointestinal disorders
Peritoneal haemorrhage
|
2.7%
1/37
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
5.4%
2/37
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
2.7%
1/37
|
|
Gastrointestinal disorders
Vomiting
|
2.7%
1/37
|
|
General disorders
Asthenia
|
13.5%
5/37
|
|
General disorders
Hypothermia
|
2.7%
1/37
|
|
General disorders
Pain
|
2.7%
1/37
|
|
General disorders
Pyrexia
|
2.7%
1/37
|
|
Hepatobiliary disorders
Hepatic cirrhosis
|
2.7%
1/37
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
5.4%
2/37
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
2.7%
1/37
|
|
Infections and infestations
Empyema
|
2.7%
1/37
|
|
Infections and infestations
Pneumonia
|
2.7%
1/37
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
2.7%
1/37
|
|
Musculoskeletal and connective tissue disorders
Hypercreatinaemia
|
2.7%
1/37
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.7%
1/37
|
|
Nervous system disorders
Aphasia
|
2.7%
1/37
|
|
Nervous system disorders
Balance disorder
|
2.7%
1/37
|
|
Nervous system disorders
Cerebrovascular accident
|
2.7%
1/37
|
|
Nervous system disorders
Coma
|
2.7%
1/37
|
|
Nervous system disorders
Depressed level of consciousness
|
2.7%
1/37
|
|
Nervous system disorders
Hepatic encephalopathy
|
8.1%
3/37
|
|
Nervous system disorders
Loss of consciousness
|
2.7%
1/37
|
|
Nervous system disorders
Nervous system disorder
|
2.7%
1/37
|
|
Nervous system disorders
Neurological decompensation
|
2.7%
1/37
|
|
Nervous system disorders
Somnolence
|
10.8%
4/37
|
|
Psychiatric disorders
Confusional state
|
5.4%
2/37
|
|
Renal and urinary disorders
Renal failure
|
2.7%
1/37
|
|
Reproductive system and breast disorders
Pelvic pain
|
2.7%
1/37
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
5.4%
2/37
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.7%
1/37
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
2.7%
1/37
|
Other adverse events
| Measure |
50 Milligram (mg) Sunitinib
n=37 participants at risk
Subjects received open-label sunitinib malate at a starting dose of 50 mg once daily for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
24.3%
9/37
|
|
Blood and lymphatic system disorders
Leukopenia
|
18.9%
7/37
|
|
Blood and lymphatic system disorders
Neutropenia
|
21.6%
8/37
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
45.9%
17/37
|
|
Ear and labyrinth disorders
Vertigo
|
5.4%
2/37
|
|
Gastrointestinal disorders
Abdominal distension
|
8.1%
3/37
|
|
Gastrointestinal disorders
Abdominal pain
|
21.6%
8/37
|
|
Gastrointestinal disorders
Abdominal pain upper
|
21.6%
8/37
|
|
Gastrointestinal disorders
Ascites
|
24.3%
9/37
|
|
Gastrointestinal disorders
Constipation
|
18.9%
7/37
|
|
Gastrointestinal disorders
Diarrhoea
|
43.2%
16/37
|
|
Gastrointestinal disorders
Dry mouth
|
8.1%
3/37
|
|
Gastrointestinal disorders
Dyspepsia
|
18.9%
7/37
|
|
Gastrointestinal disorders
Dysphagia
|
13.5%
5/37
|
|
Gastrointestinal disorders
Gastritis
|
5.4%
2/37
|
|
Gastrointestinal disorders
Gingivitis
|
5.4%
2/37
|
|
Gastrointestinal disorders
Haematemesis
|
5.4%
2/37
|
|
Gastrointestinal disorders
Haemorrhoids
|
5.4%
2/37
|
|
Gastrointestinal disorders
Melaena
|
5.4%
2/37
|
|
Gastrointestinal disorders
Mouth haemorrhage
|
5.4%
2/37
|
|
Gastrointestinal disorders
Nausea
|
45.9%
17/37
|
|
Gastrointestinal disorders
Odynophagia
|
5.4%
2/37
|
|
Gastrointestinal disorders
Stomatitis
|
24.3%
9/37
|
|
Gastrointestinal disorders
Varices oesophageal
|
10.8%
4/37
|
|
Gastrointestinal disorders
Vomiting
|
24.3%
9/37
|
|
General disorders
Asthenia
|
45.9%
17/37
|
|
General disorders
Chest pain
|
5.4%
2/37
|
|
General disorders
Face oedema
|
10.8%
4/37
|
|
General disorders
Fatigue
|
13.5%
5/37
|
|
General disorders
Malaise
|
10.8%
4/37
|
|
General disorders
Mucosal inflammation
|
18.9%
7/37
|
|
General disorders
Oedema peripheral
|
16.2%
6/37
|
|
General disorders
Pain
|
5.4%
2/37
|
|
General disorders
Pitting oedema
|
8.1%
3/37
|
|
General disorders
Pyrexia
|
18.9%
7/37
|
|
Hepatobiliary disorders
Hepatic pain
|
5.4%
2/37
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
16.2%
6/37
|
|
Infections and infestations
Bronchitis
|
5.4%
2/37
|
|
Infections and infestations
Fungal skin infection
|
8.1%
3/37
|
|
Infections and infestations
Skin infection
|
5.4%
2/37
|
|
Infections and infestations
Upper respiratory tract infection
|
8.1%
3/37
|
|
Infections and infestations
Urinary tract infection
|
8.1%
3/37
|
|
Injury, poisoning and procedural complications
Fall
|
5.4%
2/37
|
|
Investigations
Alanine aminotransferase increased
|
16.2%
6/37
|
|
Investigations
Aspartate aminotransferase increased
|
18.9%
7/37
|
|
Investigations
Blood alkaline phosphatase increased
|
8.1%
3/37
|
|
Investigations
Blood bilirubin
|
5.4%
2/37
|
|
Investigations
Gamma-glutamyltransferase increased
|
13.5%
5/37
|
|
Investigations
Haemoglobin
|
8.1%
3/37
|
|
Investigations
Platelet count
|
8.1%
3/37
|
|
Investigations
Weight decreased
|
16.2%
6/37
|
|
Investigations
White blood cell count
|
10.8%
4/37
|
|
Metabolism and nutrition disorders
Anorexia
|
45.9%
17/37
|
|
Metabolism and nutrition disorders
Dehydration
|
5.4%
2/37
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
8.1%
3/37
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
5.4%
2/37
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
5.4%
2/37
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
5.4%
2/37
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
10.8%
4/37
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
5.4%
2/37
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
8.1%
3/37
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
5.4%
2/37
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
5.4%
2/37
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
13.5%
5/37
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.4%
2/37
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
8.1%
3/37
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
5.4%
2/37
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
16.2%
6/37
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
10.8%
4/37
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
8.1%
3/37
|
|
Nervous system disorders
Ageusia
|
8.1%
3/37
|
|
Nervous system disorders
Dizziness
|
5.4%
2/37
|
|
Nervous system disorders
Dysgeusia
|
10.8%
4/37
|
|
Nervous system disorders
Headache
|
21.6%
8/37
|
|
Nervous system disorders
Neuropathy peripheral
|
5.4%
2/37
|
|
Nervous system disorders
Sciatica
|
5.4%
2/37
|
|
Psychiatric disorders
Anxiety
|
5.4%
2/37
|
|
Psychiatric disorders
Confusional state
|
5.4%
2/37
|
|
Psychiatric disorders
Insomnia
|
16.2%
6/37
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.2%
6/37
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
10.8%
4/37
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
18.9%
7/37
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
27.0%
10/37
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
5.4%
2/37
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
8.1%
3/37
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
18.9%
7/37
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.4%
2/37
|
|
Skin and subcutaneous tissue disorders
Hair colour changes
|
16.2%
6/37
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
5.4%
2/37
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
29.7%
11/37
|
|
Skin and subcutaneous tissue disorders
Periorbital oedema
|
5.4%
2/37
|
|
Skin and subcutaneous tissue disorders
Rash
|
13.5%
5/37
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
16.2%
6/37
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
5.4%
2/37
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
8.1%
3/37
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
10.8%
4/37
|
|
Vascular disorders
Hypertension
|
10.8%
4/37
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of \<60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), \<12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential info other than study results.
- Publication restrictions are in place
Restriction type: OTHER