Breast Neoplasms
Conditions
Brief summary
The purpose of this study is to compare progression free survival for SU011248 \[sutent (sunitinib malate)\] versus standard of care therapy in patients with previously treated, advanced, triple receptor negative (ER, PR, HER2) locally recurrent or metastatic breast cancer.
Interventions
DRUGSU011248
SU011248 capsules administered orally, daily in a continuous regimen, 3-week cycles, starting dose of 37.5 mg daily. 1-week treatment rests and dose reductions allowed for dose-limiting toxicity. Dose escalate SU011248 to 50-mg daily if minimal toxicities . Study will continue until disease progression. Patients randomized to or crossed over to SU011248 may continue beyond the time of Response Evaluation Criterion in Solid Tumors (RECIST) -defined progression at the discretion of the investigator in the case of clinical benefit.
DRUGChemotherapy
The choice of chemotherapy will be at the discretion of the investigator within the limits outlined below. 1. Capecitabine - 1000-1250 mg/m2 twice daily days 1-14 every 3 weeks 2. Vinorelbine - 25-30 mg/m2 rapid intravenous infusion or 60-80 mg/m2 oral weekly, expressed in 3-week cycles 3. Docetaxel - 75-100 mg/m2 every 3 weeks 4. Paclitaxel - 175-200 mg/m2 every 3 weeks 5. Paclitaxel - 80-90 mg/m2 weekly, in a continuous regimen expressed in 3-week cycles or administration of 3 weeks of treatment followed by 1 week of rest. Use of the 3/1 regimen will require extra care in scheduling disease assessments. 6. Gemcitabine - 800-1250 mg/m2 Days 1 and 8 every 3 weeks Study will continue until disease progression or it is in the best interest of the patient to discontinue based on achievement of maximum benefit or tolerability issues. At the time of progression patients randomized to chemotherapy will be offered crossover to single agent SU011248.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Recurrent or metastatic breast cancer * Estrogen receptor (ER), progestin receptor (PR) and HER2/neu receptor (HER2) negative status * Prior treatment with an anthracycline and a taxane in the adjuvant or advanced disease setting * Relapse following adjuvant chemotherapy within 6 months of last treatment and/or received one or two chemotherapy regimens for advanced disease
Exclusion criteria
* More than two chemotherapy regimens for advanced disease * Uncontrolled/symptomatic spread of cancer to the brain
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Baseline, every 6 weeks until disease progression or death (up to 3 years from first dose) | Time in months from start of study treatment to first documentation of objective tumor progression (per RECIST) or death due to any cause. PFS was calculated as (first event date minus first randomization date plus 1) divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from adverse event (AE) data (where the outcome was Death). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Objective Response | Baseline until response or disease progression (up to 3 years from first dose) | Objective response based assessment of confirmed response (CR) or confirmed partial response (PR) according to RECIST. CR are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. PR are those with a greater than or equal to (≥) 30% decrease in the sum of the longest dimensions (SLD) of the target lesions taking as a reference the baseline SLD. |
| Duration of Response (DR) | Time from first response to disease progression up to 3 years from first dose | Time in months from the first documentation of objective tumor response (CR or PR) to objective tumor progression or death. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4. DR was calculated for the subgroup of participants with a confirmed objective tumor response. |
| Overall Survival (OS) | Baseline until death (up to 3 years after first dose of study medication) | Time in months from the date of randomization to date of death due to any cause. OS was calculated as (date of death minus randomization date plus 1) divided by 30.4. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death). |
| Health Related Quality of Life (HRQoL) and Disease Related Symptoms as Measured by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (EORTC-QLQ-C30) | Day 1, Cycle 1; Day 1, odd number cycles; and end of treatment (EOT)/withdrawal | EORTC QLQ-C30: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much; global/QoL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms. |
| HRQoL and Disease Related Symptoms as Measured by EORTC-QLQ-C30 Breast Cancer Module (BR23) Score | Day 1, Cycle 1; Day 1, odd number cycles; and EOT/withdrawal | BR23: measured disease related symptoms of dry mouth, eye pain, hair loss, hot flushes, attractiveness, future health, sexual activity, arm/shoulder pain, breast pain, swollen breast, and skin problems on the breast. Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms. |
| Observed Plasma Trough Concentrations (Ctrough) of Sunitinib | Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3 | — |
| Ctrough of SU012662 (Metabolite of Sunitinib) | Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3 | — |
| Ctrough of Total Drug (Sunitinib + SU012662) | Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3 | — |
| Dose-corrected Ctrough of Sunitinib | Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3 | Ctrough = plasma concentration of sunitinib prior to study drug administration, dose corrected using the following formula Intended Dose/Actual Dose, where Actual Dose: the dose the participant received over the last 10 consecutive days and Intended Dose: the starting dose per study protocol. |
| Survival Probability at 1 Year | Baseline until death (up to 3 years after first dose of study medication) | Probability that the participants will survive at end of 1 year from the first dose of study treatment. Calculated using data collected from baseline until death (up to 3 years after first dose of study medication). Probability calculated from Kaplan-Meier estimate. |
| Dose-corrected Ctrough of Total Drug (Sunitinib + SU012662) | Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3 | Ctrough = plasma concentration of total drug (Sunitinib + SU012662) prior to study drug administration dose corrected using the following formula Intended Dose/Actual Dose, where Actual Dose: the dose the participant received over the last 10 consecutive days and Intended Dose: the starting dose per study protocol. |
| Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 2 (sVEGFR2) | Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5, and 7), and EOT/withdrawal | Plasma concentrations of sVEGFR2 were examined as a potential pharmacodynamic marker |
| Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (sVEGFR3) | Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5, and 7), and EOT/withdrawal | Plasma concentrations of sVEGFR3 were examined as a potential pharmacodynamic marker |
| Plasma Concentration of Soluble Vascular Endothelial Growth Factor A (sVEGF-A) | Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5, and 7), and EOT/withdrawal | Plasma concentrations of sVEGF-A were examined as a potential pharmacodynamic marker |
| Plasma Concentration of Soluble Placental Growth Factor (sPlGF) | Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5 and 7), and EOT/withdrawal | Plasma concentrations of sPlGF were examined as a potential pharmacodynamic marker |
| Plasma Concentration of Soluble Kinase Insert Domain for Tyrosine (sKIT), a Stem Cell Factor Receptor | Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5 and 7), and EOT/withdrawal | Plasma concentrations of sKIT were examined as a potential pharmacodynamic marker |
| Circulating Endothelial Cells (CEC) | Days 1 and 15 of Cycles 1, 2 and 3, Day 1 of Cycles 4 and 5, and every odd cycle thereafter, and EOT/withdrawal | Blood samples were collected to enumerate the number of total CECs and sVEGFR1, sVEGFR2 and sVEGFR3 protein expression and/or cellular viability. |
| Circulating Tumor Cells (CTC) | Days 1 and 15 of Cycles 1, 2 and 3, Day 1 of Cycles 4 and 5, and every odd cycle thereafter, and EOT/withdrawal | Blood samples were collected to enumerate the number of total CTCs and insulin growth factor 1R positive (IGF-1R+) CTCs |
| Dose-corrected Ctrough of SU012662 (Metabolite of Sunitinib) | Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3 | Ctrough = plasma concentration of SU012662 prior to study drug administration, dose corrected using the following formula Intended Dose/Actual Dose, where Actual Dose: the dose the participant received over the last 10 consecutive days and Intended Dose: the starting dose per study protocol. |
Countries
Bulgaria, Canada, Czechia, France, Germany, Hungary, Italy, Spain, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sunitinib SU011248 (Sutent \[sunitinib malate, hereafter referred to as sunitinib\]) oral capsules, 37.5 milligrams (mg) once daily (QD) in a continuous regimen, expressed in 3-week cycles. 1-week treatment rests and dose reductions allowed for dose-limiting toxicity (DLT). Dose escalated to sunitinib 50 mg QD if minimal toxicities. | 113 |
| Standard of Care One of the following regimens was administered (at investigator's discretion): oral capecitabine 1000-1250 mg/m\^2 BID Days 1-14, every 3 weeks; vinorelbine 25-30 mg/m\^2 rapid IV infusion or 60-80 mg/m\^2 oral weekly, expressed in 3-week cycles; docetaxel 75-100 mg/m\^2 via IV infusion every 3 weeks; paclitaxel 175-200 mg/m\^2 via IV infusion every 3 weeks; paclitaxel 80-90 mg/m\^2 weekly, in a continuous regimen expressed in 3-week cycles or 3 weeks of treatment followed by 1 week of rest; gemcitabine 800-1250 mg/m\^2 via IV infusion, Days 1 and 8 every 3 weeks. If RECIST defined progression was met, participants could receive sunitinib, 37.5 mg oral capsules QD, in continuous 3-week cycles. | 104 |
| Total | 217 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 0 |
| Overall Study | Crossover participants | 0 | 74 |
| Overall Study | Death | 17 | 3 |
| Overall Study | Did not meet entrance criteria | 2 | 1 |
| Overall Study | Laboratory abnormalities | 1 | 0 |
| Overall Study | Lack of Efficacy | 84 | 21 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Sponsor | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Sunitinib | Standard of Care | Total |
|---|---|---|---|
| Age, Customized Greater than or equal to 65 years | 10 Participants | 14 Participants | 24 Participants |
| Age, Customized Less than 65 years | 103 Participants | 90 Participants | 193 Participants |
| Sex: Female, Male Female | 113 Participants | 104 Participants | 217 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 109 / 110 | 98 / 103 |
| serious Total, serious adverse events | 40 / 110 | 21 / 103 |
Outcome results
Primary
Progression-Free Survival (PFS)
Time in months from start of study treatment to first documentation of objective tumor progression (per RECIST) or death due to any cause. PFS was calculated as (first event date minus first randomization date plus 1) divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from adverse event (AE) data (where the outcome was Death).
Time frame: Baseline, every 6 weeks until disease progression or death (up to 3 years from first dose)
Population: Intent-to-Treat (ITT) population: all participants who were randomized.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sunitinib | Progression-Free Survival (PFS) | Core radiology laboratory assessment | 2.0 Months |
| Sunitinib | Progression-Free Survival (PFS) | Investigator's assessment | 1.7 Months |
| Standard of Care | Progression-Free Survival (PFS) | Core radiology laboratory assessment | 2.7 Months |
| Standard of Care | Progression-Free Survival (PFS) | Investigator's assessment | 2.5 Months |
Comparison: For core radiology laboratory assessmentp-value: 0.888595% CI: [0.8889, 1.628]Log Rank
Comparison: For investigator's assessmentp-value: 0.847295% CI: [0.8703, 1.5457]Log Rank
Secondary
Circulating Endothelial Cells (CEC)
Blood samples were collected to enumerate the number of total CECs and sVEGFR1, sVEGFR2 and sVEGFR3 protein expression and/or cellular viability.
Time frame: Days 1 and 15 of Cycles 1, 2 and 3, Day 1 of Cycles 4 and 5, and every odd cycle thereafter, and EOT/withdrawal
Population: ITT population. n = participants with available data at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib | Circulating Endothelial Cells (CEC) | Cycle 1, Day 15 (n=28, 37) | 630 cells/mL | Standard Deviation 1210.431 |
| Sunitinib | Circulating Endothelial Cells (CEC) | Cycle 3, Day 15 (n=4, 1) | 923.85 cells/mL | Standard Deviation 1274.882 |
| Sunitinib | Circulating Endothelial Cells (CEC) | Cycle 2, Day 15 (n=7, 5) | 1310.86 cells/mL | Standard Deviation 725.107 |
| Sunitinib | Circulating Endothelial Cells (CEC) | Cycle 4, Day 1 (n=3, 5) | 169.24 cells/mL | Standard Deviation 73.614 |
| Sunitinib | Circulating Endothelial Cells (CEC) | Cycle 2, Day 1 (n=33, 35) | 512.39 cells/mL | Standard Deviation 790.018 |
| Sunitinib | Circulating Endothelial Cells (CEC) | Cycle 5, Day 1 (n=2, 2) | 145.68 cells/mL | Standard Deviation 178.643 |
| Sunitinib | Circulating Endothelial Cells (CEC) | Cycle 3, Day 1 (n=27, 25) | 390.09 cells/mL | Standard Deviation 490.173 |
| Sunitinib | Circulating Endothelial Cells (CEC) | EOT (n=18, 18) | 477.83 cells/mL | Standard Deviation 780.161 |
| Sunitinib | Circulating Endothelial Cells (CEC) | Cycle 1, Day 1 (n=42, 48) | 944.67 cells/mL | Standard Deviation 1784.549 |
| Standard of Care | Circulating Endothelial Cells (CEC) | EOT (n=18, 18) | 1087.94 cells/mL | Standard Deviation 1713.581 |
| Standard of Care | Circulating Endothelial Cells (CEC) | Cycle 1, Day 1 (n=42, 48) | 1176.92 cells/mL | Standard Deviation 2704.135 |
| Standard of Care | Circulating Endothelial Cells (CEC) | Cycle 1, Day 15 (n=28, 37) | 1199.32 cells/mL | Standard Deviation 2334.643 |
| Standard of Care | Circulating Endothelial Cells (CEC) | Cycle 2, Day 1 (n=33, 35) | 1048.31 cells/mL | Standard Deviation 2415.424 |
| Standard of Care | Circulating Endothelial Cells (CEC) | Cycle 2, Day 15 (n=7, 5) | 852.96 cells/mL | Standard Deviation 438.779 |
| Standard of Care | Circulating Endothelial Cells (CEC) | Cycle 3, Day 1 (n=27, 25) | 509.75 cells/mL | Standard Deviation 665.236 |
| Standard of Care | Circulating Endothelial Cells (CEC) | Cycle 3, Day 15 (n=4, 1) | 231.80 cells/mL | Standard Deviation 0 |
| Standard of Care | Circulating Endothelial Cells (CEC) | Cycle 4, Day 1 (n=3, 5) | 976.79 cells/mL | Standard Deviation 1185.18 |
| Standard of Care | Circulating Endothelial Cells (CEC) | Cycle 5, Day 1 (n=2, 2) | 2031.67 cells/mL | Standard Deviation 105.932 |
Secondary
Circulating Tumor Cells (CTC)
Blood samples were collected to enumerate the number of total CTCs and insulin growth factor 1R positive (IGF-1R+) CTCs
Time frame: Days 1 and 15 of Cycles 1, 2 and 3, Day 1 of Cycles 4 and 5, and every odd cycle thereafter, and EOT/withdrawal
Population: ITT population. n = participants with available data at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib | Circulating Tumor Cells (CTC) | Cycle 2, Day 1 (n=19, 17) | 189 cells/7.5 mL | Standard Deviation 701.533 |
| Sunitinib | Circulating Tumor Cells (CTC) | Cycle 3, Day 15 (n=2, 4) | 40.50 cells/7.5 mL | Standard Deviation 28.991 |
| Sunitinib | Circulating Tumor Cells (CTC) | Cycle 1, Day 1 (n=33, 28) | 119.76 cells/7.5 mL | Standard Deviation 495.731 |
| Sunitinib | Circulating Tumor Cells (CTC) | Cycle 4, Day 1 (n=2, 5) | 61 cells/7.5 mL | Standard Deviation 0 |
| Sunitinib | Circulating Tumor Cells (CTC) | Cycle 2, Day 15 (n=3, 7) | 33.33 cells/7.5 mL | Standard Deviation 50.143 |
| Sunitinib | Circulating Tumor Cells (CTC) | Cycle 5, Day 1 (n=2, 3) | 19.50 cells/7.5 mL | Standard Deviation 23.335 |
| Sunitinib | Circulating Tumor Cells (CTC) | Cycle 1, Day 15 (n=20, 16) | 183.60 cells/7.5 mL | Standard Deviation 672.994 |
| Sunitinib | Circulating Tumor Cells (CTC) | EOT (n=17,4) | 55 cells/7.5 mL | Standard Deviation 105.796 |
| Sunitinib | Circulating Tumor Cells (CTC) | Cycle 3, Day 1 (n=8, 15) | 36.50 cells/7.5 mL | Standard Deviation 40.918 |
| Standard of Care | Circulating Tumor Cells (CTC) | EOT (n=17,4) | 3 cells/7.5 mL | Standard Deviation 4 |
| Standard of Care | Circulating Tumor Cells (CTC) | Cycle 1, Day 15 (n=20, 16) | 10.69 cells/7.5 mL | Standard Deviation 24.811 |
| Standard of Care | Circulating Tumor Cells (CTC) | Cycle 2, Day 1 (n=19, 17) | 3.18 cells/7.5 mL | Standard Deviation 6.317 |
| Standard of Care | Circulating Tumor Cells (CTC) | Cycle 2, Day 15 (n=3, 7) | 0.86 cells/7.5 mL | Standard Deviation 1.215 |
| Standard of Care | Circulating Tumor Cells (CTC) | Cycle 3, Day 1 (n=8, 15) | 10.60 cells/7.5 mL | Standard Deviation 28.045 |
| Standard of Care | Circulating Tumor Cells (CTC) | Cycle 3, Day 15 (n=2, 4) | 0 cells/7.5 mL | Standard Deviation 0 |
| Standard of Care | Circulating Tumor Cells (CTC) | Cycle 4, Day 1 (n=2, 5) | 0.60 cells/7.5 mL | Standard Deviation 1.342 |
| Standard of Care | Circulating Tumor Cells (CTC) | Cycle 5, Day 1 (n=2, 3) | 0.33 cells/7.5 mL | Standard Deviation 0.577 |
| Standard of Care | Circulating Tumor Cells (CTC) | Cycle 1, Day 1 (n=33, 28) | 17.71 cells/7.5 mL | Standard Deviation 44.139 |
Secondary
Ctrough of SU012662 (Metabolite of Sunitinib)
Time frame: Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3
Population: ITT population. n = number of participants with available data for those time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib | Ctrough of SU012662 (Metabolite of Sunitinib) | Cycle 1, Day 1 (n=54) | 0.02 ng/mL | Standard Deviation 0.16 |
| Sunitinib | Ctrough of SU012662 (Metabolite of Sunitinib) | Cycle 1, Day 15 (n=44) | 29.4 ng/mL | Standard Deviation 10.99 |
| Sunitinib | Ctrough of SU012662 (Metabolite of Sunitinib) | Cycle 2, Day 1 (n=42) | 32.3 ng/mL | Standard Deviation 17.21 |
| Sunitinib | Ctrough of SU012662 (Metabolite of Sunitinib) | Cycle 2, Day 15 (n=33) | 33.4 ng/mL | Standard Deviation 20.75 |
| Sunitinib | Ctrough of SU012662 (Metabolite of Sunitinib) | Cycle 3, Day 1 (n=26) | 28.5 ng/mL | Standard Deviation 21.91 |
| Sunitinib | Ctrough of SU012662 (Metabolite of Sunitinib) | Cycle 3, Day 15 (n=21) | 40.4 ng/mL | Standard Deviation 15.33 |
| Sunitinib | Ctrough of SU012662 (Metabolite of Sunitinib) | Cycle 4, Day 1 (n=18) | 30.9 ng/mL | Standard Deviation 19.06 |
| Sunitinib | Ctrough of SU012662 (Metabolite of Sunitinib) | Cycle 5, Day 1 (n=12) | 36.1 ng/mL | Standard Deviation 22.01 |
| Sunitinib | Ctrough of SU012662 (Metabolite of Sunitinib) | Cycle 7, Day 1 (n=6) | 21.3 ng/mL | Standard Deviation 5.06 |
Secondary
Ctrough of Total Drug (Sunitinib + SU012662)
Time frame: Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3
Population: ITT population. n = number of participants with available data for those time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib | Ctrough of Total Drug (Sunitinib + SU012662) | Cycle 1, Day 1 (n=54) | 0.14 ng/mL | Standard Deviation 1.05 |
| Sunitinib | Ctrough of Total Drug (Sunitinib + SU012662) | Cycle 1, Day 15 (n=44) | 94.9 ng/mL | Standard Deviation 38.43 |
| Sunitinib | Ctrough of Total Drug (Sunitinib + SU012662) | Cycle 2, Day 1 (n=42) | 94.4 ng/mL | Standard Deviation 51.24 |
| Sunitinib | Ctrough of Total Drug (Sunitinib + SU012662) | Cycle 2, Day 15 (n=33) | 91.6 ng/mL | Standard Deviation 46.27 |
| Sunitinib | Ctrough of Total Drug (Sunitinib + SU012662) | Cycle 3, Day 1 (n=26) | 78.6 ng/mL | Standard Deviation 53.15 |
| Sunitinib | Ctrough of Total Drug (Sunitinib + SU012662) | Cycle 3, Day 15 (n=21) | 105 ng/mL | Standard Deviation 39.99 |
| Sunitinib | Ctrough of Total Drug (Sunitinib + SU012662) | Cycle 4, Day 1 (n=18) | 82.2 ng/mL | Standard Deviation 48.56 |
| Sunitinib | Ctrough of Total Drug (Sunitinib + SU012662) | Cycle 5, Day 1 (n=12) | 84.2 ng/mL | Standard Deviation 42.66 |
| Sunitinib | Ctrough of Total Drug (Sunitinib + SU012662) | Cycle 7, Day 1 (n=6) | 63.6 ng/mL | Standard Deviation 24.64 |
Secondary
Dose-corrected Ctrough of SU012662 (Metabolite of Sunitinib)
Ctrough = plasma concentration of SU012662 prior to study drug administration, dose corrected using the following formula Intended Dose/Actual Dose, where Actual Dose: the dose the participant received over the last 10 consecutive days and Intended Dose: the starting dose per study protocol.
Time frame: Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3
Population: ITT population. n = number of participants with available data for those time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib | Dose-corrected Ctrough of SU012662 (Metabolite of Sunitinib) | Cycle 1, Day 1 (n=ND) | NA ng/mL | — |
| Sunitinib | Dose-corrected Ctrough of SU012662 (Metabolite of Sunitinib) | Cycle 1, Day 15 (n=44) | 29.9 ng/mL | Standard Deviation 10.14 |
| Sunitinib | Dose-corrected Ctrough of SU012662 (Metabolite of Sunitinib) | Cycle 2, Day 1 (n=42) | 37.2 ng/mL | Standard Deviation 13.33 |
| Sunitinib | Dose-corrected Ctrough of SU012662 (Metabolite of Sunitinib) | Cycle 2, Day 15 (n=33) | 37.3 ng/mL | Standard Deviation 20.72 |
| Sunitinib | Dose-corrected Ctrough of SU012662 (Metabolite of Sunitinib) | Cycle 3, Day 1 (n=26) | 39.8 ng/mL | Standard Deviation 21.58 |
| Sunitinib | Dose-corrected Ctrough of SU012662 (Metabolite of Sunitinib) | Cycle 3, Day 15 (n=21) | 40.1 ng/mL | Standard Deviation 14.55 |
| Sunitinib | Dose-corrected Ctrough of SU012662 (Metabolite of Sunitinib) | Cycle 4, Day 1 (n=18) | 38.7 ng/mL | Standard Deviation 17.58 |
| Sunitinib | Dose-corrected Ctrough of SU012662 (Metabolite of Sunitinib) | Cycle 5, Day 1 (n=12) | 41.9 ng/mL | Standard Deviation 19.95 |
| Sunitinib | Dose-corrected Ctrough of SU012662 (Metabolite of Sunitinib) | Cycle 7, Day 1 (n=6) | 28.6 ng/mL | Standard Deviation 7.86 |
Secondary
Dose-corrected Ctrough of Sunitinib
Ctrough = plasma concentration of sunitinib prior to study drug administration, dose corrected using the following formula Intended Dose/Actual Dose, where Actual Dose: the dose the participant received over the last 10 consecutive days and Intended Dose: the starting dose per study protocol.
Time frame: Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3
Population: ITT population. n = number of participants with available data for those time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib | Dose-corrected Ctrough of Sunitinib | Cycle 3, Day 15 (n=21) | 65.3 ng/mL | Standard Deviation 29.72 |
| Sunitinib | Dose-corrected Ctrough of Sunitinib | Cycle 4, Day 1 (n=18) | 68.7 ng/mL | Standard Deviation 34.28 |
| Sunitinib | Dose-corrected Ctrough of Sunitinib | Cycle 1, Day 1 (n=ND) | NA ng/mL | — |
| Sunitinib | Dose-corrected Ctrough of Sunitinib | Cycle 1, Day 15 (n=44) | 67.5 ng/mL | Standard Deviation 28.78 |
| Sunitinib | Dose-corrected Ctrough of Sunitinib | Cycle 2, Day 1 (n=42) | 73.4 ng/mL | Standard Deviation 29.7 |
| Sunitinib | Dose-corrected Ctrough of Sunitinib | Cycle 2, Day 15 (n=33) | 69.8 ng/mL | Standard Deviation 32.67 |
| Sunitinib | Dose-corrected Ctrough of Sunitinib | Cycle 3, Day 1 (n=26) | 69.3 ng/mL | Standard Deviation 30.08 |
| Sunitinib | Dose-corrected Ctrough of Sunitinib | Cycle 5, Day 1 (n=12) | 58.4 ng/mL | Standard Deviation 27.14 |
| Sunitinib | Dose-corrected Ctrough of Sunitinib | Cycle 7, Day 1 (n=6) | 64.0 ng/mL | Standard Deviation 46.99 |
Secondary
Dose-corrected Ctrough of Total Drug (Sunitinib + SU012662)
Ctrough = plasma concentration of total drug (Sunitinib + SU012662) prior to study drug administration dose corrected using the following formula Intended Dose/Actual Dose, where Actual Dose: the dose the participant received over the last 10 consecutive days and Intended Dose: the starting dose per study protocol.
Time frame: Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3
Population: ITT population. n = number of participants with available data for those time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib | Dose-corrected Ctrough of Total Drug (Sunitinib + SU012662) | Cycle 1, Day 15 (n=44) | 97.4 ng/mL | Standard Deviation 35.09 |
| Sunitinib | Dose-corrected Ctrough of Total Drug (Sunitinib + SU012662) | Cycle 2, Day 1 (n=42) | 111 ng/mL | Standard Deviation 38.18 |
| Sunitinib | Dose-corrected Ctrough of Total Drug (Sunitinib + SU012662) | Cycle 1, Day 1 (n=ND) | NA ng/mL | — |
| Sunitinib | Dose-corrected Ctrough of Total Drug (Sunitinib + SU012662) | Cycle 2, Day 15 (n=33) | 107 ng/mL | Standard Deviation 48.08 |
| Sunitinib | Dose-corrected Ctrough of Total Drug (Sunitinib + SU012662) | Cycle 3, Day 1 (n=26) | 109 ng/mL | Standard Deviation 44.98 |
| Sunitinib | Dose-corrected Ctrough of Total Drug (Sunitinib + SU012662) | Cycle 3, Day 15 (n=21) | 105 ng/mL | Standard Deviation 39.64 |
| Sunitinib | Dose-corrected Ctrough of Total Drug (Sunitinib + SU012662) | Cycle 4, Day 1 (n=18) | 107 ng/mL | Standard Deviation 46.13 |
| Sunitinib | Dose-corrected Ctrough of Total Drug (Sunitinib + SU012662) | Cycle 5, Day 1 (n=12) | 100 ng/mL | Standard Deviation 39.32 |
| Sunitinib | Dose-corrected Ctrough of Total Drug (Sunitinib + SU012662) | Cycle 7, Day 1 (n=6) | 92.5 ng/mL | Standard Deviation 52.82 |
Secondary
Duration of Response (DR)
Time in months from the first documentation of objective tumor response (CR or PR) to objective tumor progression or death. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Time frame: Time from first response to disease progression up to 3 years from first dose
Population: ITT population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sunitinib | Duration of Response (DR) | Core radiology assessment (n=3,7) | 3.0 months |
| Sunitinib | Duration of Response (DR) | Investigator's assessment (n=10,12) | 3.6 months |
| Standard of Care | Duration of Response (DR) | Core radiology assessment (n=3,7) | NA months |
| Standard of Care | Duration of Response (DR) | Investigator's assessment (n=10,12) | 4.6 months |
Secondary
Health Related Quality of Life (HRQoL) and Disease Related Symptoms as Measured by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (EORTC-QLQ-C30)
EORTC QLQ-C30: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much; global/QoL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
Time frame: Day 1, Cycle 1; Day 1, odd number cycles; and end of treatment (EOT)/withdrawal
Population: This participant-reported outcome was not analyzed for this report because the study did not meet its primary endpoint.
Secondary
HRQoL and Disease Related Symptoms as Measured by EORTC-QLQ-C30 Breast Cancer Module (BR23) Score
BR23: measured disease related symptoms of dry mouth, eye pain, hair loss, hot flushes, attractiveness, future health, sexual activity, arm/shoulder pain, breast pain, swollen breast, and skin problems on the breast. Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.
Time frame: Day 1, Cycle 1; Day 1, odd number cycles; and EOT/withdrawal
Population: This participant-reported outcome was not analyzed for this report because the study did not meet its primary endpoint.
Secondary
Observed Plasma Trough Concentrations (Ctrough) of Sunitinib
Time frame: Predose Day 1, Cycles 1, 2, 3, 4, 5 and 7 and Day 15 of Cycles 1, 2, and 3
Population: ITT population. n = number of participants with available data for those time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib | Observed Plasma Trough Concentrations (Ctrough) of Sunitinib | Cycle 1, Day 1 (n=54) | 0.12 ng/mL | Standard Deviation 0.9 |
| Sunitinib | Observed Plasma Trough Concentrations (Ctrough) of Sunitinib | Cycle 1, Day 15 (n=44) | 65.53 ng/mL | Standard Deviation 30.64 |
| Sunitinib | Observed Plasma Trough Concentrations (Ctrough) of Sunitinib | Cycle 2, Day 1 (n=42) | 62.09 ng/mL | Standard Deviation 37.02 |
| Sunitinib | Observed Plasma Trough Concentrations (Ctrough) of Sunitinib | Cycle 2, Day 15 (n=33) | 58.20 ng/mL | Standard Deviation 29.67 |
| Sunitinib | Observed Plasma Trough Concentrations (Ctrough) of Sunitinib | Cycle 3, Day 1 (n=26) | 50.03 ng/mL | Standard Deviation 35.56 |
| Sunitinib | Observed Plasma Trough Concentrations (Ctrough) of Sunitinib | Cycle 3, Day 15 (n=21) | 64.61 ng/mL | Standard Deviation 28.75 |
| Sunitinib | Observed Plasma Trough Concentrations (Ctrough) of Sunitinib | Cycle 4, Day 1 (n=18) | 51.25 ng/mL | Standard Deviation 32.88 |
| Sunitinib | Observed Plasma Trough Concentrations (Ctrough) of Sunitinib | Cycle 5, Day 1 (n=12) | 48.07 ng/mL | Standard Deviation 24.74 |
| Sunitinib | Observed Plasma Trough Concentrations (Ctrough) of Sunitinib | Cycle 7, Day 1 (n=6) | 42.23 ng/mL | Standard Deviation 22.88 |
Secondary
Overall Survival (OS)
Time in months from the date of randomization to date of death due to any cause. OS was calculated as (date of death minus randomization date plus 1) divided by 30.4. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).
Time frame: Baseline until death (up to 3 years after first dose of study medication)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib | Overall Survival (OS) | 9.4 months |
| Standard of Care | Overall Survival (OS) | 10.5 months |
p-value: 0.839495% CI: [0.8648, 1.5558]Log Rank
Secondary
Plasma Concentration of Soluble Kinase Insert Domain for Tyrosine (sKIT), a Stem Cell Factor Receptor
Plasma concentrations of sKIT were examined as a potential pharmacodynamic marker
Time frame: Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5 and 7), and EOT/withdrawal
Population: ITT population. n = participants with available data at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib | Plasma Concentration of Soluble Kinase Insert Domain for Tyrosine (sKIT), a Stem Cell Factor Receptor | End Of Treatment (n=49, 11) | 25004.08 pg/mL | Standard Deviation 13431.632 |
| Sunitinib | Plasma Concentration of Soluble Kinase Insert Domain for Tyrosine (sKIT), a Stem Cell Factor Receptor | Cycle 4 Day 1 (n=33, 27) | 25887.88 pg/mL | Standard Deviation 13895.183 |
| Sunitinib | Plasma Concentration of Soluble Kinase Insert Domain for Tyrosine (sKIT), a Stem Cell Factor Receptor | Cycle 2 Day 1 (n=66, 48) | 44987.88 pg/mL | Standard Deviation 25631.702 |
| Sunitinib | Plasma Concentration of Soluble Kinase Insert Domain for Tyrosine (sKIT), a Stem Cell Factor Receptor | Cycle 5 Day 1 (n=28, 19) | 21696.07 pg/mL | Standard Deviation 12011.95 |
| Sunitinib | Plasma Concentration of Soluble Kinase Insert Domain for Tyrosine (sKIT), a Stem Cell Factor Receptor | Cycle 1 Day 1 (n=83, 64) | 61862.65 pg/mL | Standard Deviation 21839.664 |
| Sunitinib | Plasma Concentration of Soluble Kinase Insert Domain for Tyrosine (sKIT), a Stem Cell Factor Receptor | Cycle 7 Day 1 (n=9, 8) | 18166.67 pg/mL | Standard Deviation 5406.246 |
| Sunitinib | Plasma Concentration of Soluble Kinase Insert Domain for Tyrosine (sKIT), a Stem Cell Factor Receptor | Cycle 3 Day 1 (n=49, 35) | 30855.10 pg/mL | Standard Deviation 12403.495 |
| Standard of Care | Plasma Concentration of Soluble Kinase Insert Domain for Tyrosine (sKIT), a Stem Cell Factor Receptor | End Of Treatment (n=49, 11) | 72854.55 pg/mL | Standard Deviation 52888.909 |
| Standard of Care | Plasma Concentration of Soluble Kinase Insert Domain for Tyrosine (sKIT), a Stem Cell Factor Receptor | Cycle 1 Day 1 (n=83, 64) | 62232.81 pg/mL | Standard Deviation 25231.645 |
| Standard of Care | Plasma Concentration of Soluble Kinase Insert Domain for Tyrosine (sKIT), a Stem Cell Factor Receptor | Cycle 2 Day 1 (n=66, 48) | 65843.75 pg/mL | Standard Deviation 28889.26 |
| Standard of Care | Plasma Concentration of Soluble Kinase Insert Domain for Tyrosine (sKIT), a Stem Cell Factor Receptor | Cycle 3 Day 1 (n=49, 35) | 63582.86 pg/mL | Standard Deviation 22411.007 |
| Standard of Care | Plasma Concentration of Soluble Kinase Insert Domain for Tyrosine (sKIT), a Stem Cell Factor Receptor | Cycle 4 Day 1 (n=33, 27) | 62885.19 pg/mL | Standard Deviation 20790.173 |
| Standard of Care | Plasma Concentration of Soluble Kinase Insert Domain for Tyrosine (sKIT), a Stem Cell Factor Receptor | Cycle 5 Day 1 (n=28, 19) | 54811.05 pg/mL | Standard Deviation 14542.905 |
| Standard of Care | Plasma Concentration of Soluble Kinase Insert Domain for Tyrosine (sKIT), a Stem Cell Factor Receptor | Cycle 7 Day 1 (n=9, 8) | 56237.50 pg/mL | Standard Deviation 10577.056 |
Secondary
Plasma Concentration of Soluble Placental Growth Factor (sPlGF)
Plasma concentrations of sPlGF were examined as a potential pharmacodynamic marker
Time frame: Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5 and 7), and EOT/withdrawal
Population: ITT population. n = participants with available data at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib | Plasma Concentration of Soluble Placental Growth Factor (sPlGF) | Cycle 3 Day 1 (n=5, 4) | 72.16 pg/mL | Standard Deviation 30.436 |
| Sunitinib | Plasma Concentration of Soluble Placental Growth Factor (sPlGF) | Cycle 5 Day 1 (n=1, 3) | 118.30 pg/mL | Standard Deviation 0 |
| Sunitinib | Plasma Concentration of Soluble Placental Growth Factor (sPlGF) | Cycle 2 Day 1 (n=11, 9) | 168.05 pg/mL | Standard Deviation 168.643 |
| Sunitinib | Plasma Concentration of Soluble Placental Growth Factor (sPlGF) | Cycle 7 Day 1 (n=1, 1) | 176.60 pg/mL | Standard Deviation 0 |
| Sunitinib | Plasma Concentration of Soluble Placental Growth Factor (sPlGF) | Cycle 4 Day 1 (n=2, 3) | 144.60 pg/mL | Standard Deviation 4.384 |
| Sunitinib | Plasma Concentration of Soluble Placental Growth Factor (sPlGF) | End Of Treatment (n=5, 0) | 87.54 pg/mL | Standard Deviation 75.665 |
| Sunitinib | Plasma Concentration of Soluble Placental Growth Factor (sPlGF) | Cycle 1 Day 1 (n=15, 11) | 36.96 pg/mL | Standard Deviation 13.677 |
| Standard of Care | Plasma Concentration of Soluble Placental Growth Factor (sPlGF) | End Of Treatment (n=5, 0) | 0 pg/mL | Standard Deviation 0 |
| Standard of Care | Plasma Concentration of Soluble Placental Growth Factor (sPlGF) | Cycle 1 Day 1 (n=15, 11) | 37.23 pg/mL | Standard Deviation 7.007 |
| Standard of Care | Plasma Concentration of Soluble Placental Growth Factor (sPlGF) | Cycle 2 Day 1 (n=11, 9) | 36.24 pg/mL | Standard Deviation 5.778 |
| Standard of Care | Plasma Concentration of Soluble Placental Growth Factor (sPlGF) | Cycle 3 Day 1 (n=5, 4) | 40.08 pg/mL | Standard Deviation 11.539 |
| Standard of Care | Plasma Concentration of Soluble Placental Growth Factor (sPlGF) | Cycle 4 Day 1 (n=2, 3) | 33.23 pg/mL | Standard Deviation 6.17 |
| Standard of Care | Plasma Concentration of Soluble Placental Growth Factor (sPlGF) | Cycle 5 Day 1 (n=1, 3) | 51.83 pg/mL | Standard Deviation 10.385 |
| Standard of Care | Plasma Concentration of Soluble Placental Growth Factor (sPlGF) | Cycle 7 Day 1 (n=1, 1) | 38.50 pg/mL | Standard Deviation 0 |
Secondary
Plasma Concentration of Soluble Vascular Endothelial Growth Factor A (sVEGF-A)
Plasma concentrations of sVEGF-A were examined as a potential pharmacodynamic marker
Time frame: Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5, and 7), and EOT/withdrawal
Population: ITT population. n = participants with available data at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib | Plasma Concentration of Soluble Vascular Endothelial Growth Factor A (sVEGF-A) | Cycle 3 Day 1 (n=49, 37) | 265.56 pg/mL | Standard Deviation 235.166 |
| Sunitinib | Plasma Concentration of Soluble Vascular Endothelial Growth Factor A (sVEGF-A) | Cycle 5 Day 1 (n=28, 20) | 324.09 pg/mL | Standard Deviation 281.943 |
| Sunitinib | Plasma Concentration of Soluble Vascular Endothelial Growth Factor A (sVEGF-A) | Cycle 2 Day 1 (n=67, 50) | 455.17 pg/mL | Standard Deviation 704.062 |
| Sunitinib | Plasma Concentration of Soluble Vascular Endothelial Growth Factor A (sVEGF-A) | Cycle 7 Day 1 (n=9, 10) | 241.78 pg/mL | Standard Deviation 148.593 |
| Sunitinib | Plasma Concentration of Soluble Vascular Endothelial Growth Factor A (sVEGF-A) | Cycle 4 Day 1 (n=33, 28) | 274.94 pg/mL | Standard Deviation 226.763 |
| Sunitinib | Plasma Concentration of Soluble Vascular Endothelial Growth Factor A (sVEGF-A) | End Of Treatment (n=49, 12) | 294.66 pg/mL | Standard Deviation 675.063 |
| Sunitinib | Plasma Concentration of Soluble Vascular Endothelial Growth Factor A (sVEGF-A) | Cycle 1 Day 1 (n=83, 66) | 152.28 pg/mL | Standard Deviation 189.204 |
| Standard of Care | Plasma Concentration of Soluble Vascular Endothelial Growth Factor A (sVEGF-A) | End Of Treatment (n=49, 12) | 94.76 pg/mL | Standard Deviation 89.677 |
| Standard of Care | Plasma Concentration of Soluble Vascular Endothelial Growth Factor A (sVEGF-A) | Cycle 1 Day 1 (n=83, 66) | 151.49 pg/mL | Standard Deviation 170.322 |
| Standard of Care | Plasma Concentration of Soluble Vascular Endothelial Growth Factor A (sVEGF-A) | Cycle 2 Day 1 (n=67, 50) | 170.43 pg/mL | Standard Deviation 174.635 |
| Standard of Care | Plasma Concentration of Soluble Vascular Endothelial Growth Factor A (sVEGF-A) | Cycle 3 Day 1 (n=49, 37) | 129.31 pg/mL | Standard Deviation 140.943 |
| Standard of Care | Plasma Concentration of Soluble Vascular Endothelial Growth Factor A (sVEGF-A) | Cycle 4 Day 1 (n=33, 28) | 129.88 pg/mL | Standard Deviation 131.303 |
| Standard of Care | Plasma Concentration of Soluble Vascular Endothelial Growth Factor A (sVEGF-A) | Cycle 5 Day 1 (n=28, 20) | 126.97 pg/mL | Standard Deviation 135.604 |
| Standard of Care | Plasma Concentration of Soluble Vascular Endothelial Growth Factor A (sVEGF-A) | Cycle 7 Day 1 (n=9, 10) | 115.58 pg/mL | Standard Deviation 96.101 |
Secondary
Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 2 (sVEGFR2)
Plasma concentrations of sVEGFR2 were examined as a potential pharmacodynamic marker
Time frame: Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5, and 7), and EOT/withdrawal
Population: ITT population. This outcome measure was not analyzed.
Secondary
Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (sVEGFR3)
Plasma concentrations of sVEGFR3 were examined as a potential pharmacodynamic marker
Time frame: Baseline (Cycle 1, Day 1), Day 1 (Cycles 2, 3, 4, 5, and 7), and EOT/withdrawal
Population: ITT population. n = participants with available data at that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib | Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (sVEGFR3) | Cycle 3 Day 1 (n=48, 35) | 14459.38 pg/mL | Standard Deviation 9830.743 |
| Sunitinib | Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (sVEGFR3) | Cycle 5 Day 1 (n=28, 20) | 16345.36 pg/mL | Standard Deviation 19710.783 |
| Sunitinib | Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (sVEGFR3) | Cycle 2 Day 1 (n=66, 48) | 16299.70 pg/mL | Standard Deviation 13603.54 |
| Sunitinib | Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (sVEGFR3) | Cycle 7 Day 1 (n=9, 9) | 24795.56 pg/mL | Standard Deviation 44213.992 |
| Sunitinib | Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (sVEGFR3) | Cycle 4 Day 1 (n=32, 27) | 13702.81 pg/mL | Standard Deviation 13625.71 |
| Sunitinib | Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (sVEGFR3) | End Of Treatment (n=48, 10) | 26746.46 pg/mL | Standard Deviation 45358.59 |
| Sunitinib | Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (sVEGFR3) | Cycle 1 Day 1 (n=83, 64) | 24124.82 pg/mL | Standard Deviation 13258.718 |
| Standard of Care | Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (sVEGFR3) | End Of Treatment (n=48, 10) | 29194 pg/mL | Standard Deviation 16686.909 |
| Standard of Care | Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (sVEGFR3) | Cycle 1 Day 1 (n=83, 64) | 25857.19 pg/mL | Standard Deviation 11164.091 |
| Standard of Care | Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (sVEGFR3) | Cycle 2 Day 1 (n=66, 48) | 24515.83 pg/mL | Standard Deviation 11335.285 |
| Standard of Care | Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (sVEGFR3) | Cycle 3 Day 1 (n=48, 35) | 29034.86 pg/mL | Standard Deviation 13106.527 |
| Standard of Care | Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (sVEGFR3) | Cycle 4 Day 1 (n=32, 27) | 27929.63 pg/mL | Standard Deviation 11051.566 |
| Standard of Care | Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (sVEGFR3) | Cycle 5 Day 1 (n=28, 20) | 32949 pg/mL | Standard Deviation 13113.402 |
| Standard of Care | Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (sVEGFR3) | Cycle 7 Day 1 (n=9, 9) | 32004.44 pg/mL | Standard Deviation 15886.981 |
Secondary
Proportion of Participants With Objective Response
Objective response based assessment of confirmed response (CR) or confirmed partial response (PR) according to RECIST. CR are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. PR are those with a greater than or equal to (≥) 30% decrease in the sum of the longest dimensions (SLD) of the target lesions taking as a reference the baseline SLD.
Time frame: Baseline until response or disease progression (up to 3 years from first dose)
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib | Proportion of Participants With Objective Response | Core radiology laboratory assessment | 2.7 percentage of participants |
| Sunitinib | Proportion of Participants With Objective Response | Investigator's assessment | 8.8 percentage of participants |
| Standard of Care | Proportion of Participants With Objective Response | Core radiology laboratory assessment | 6.7 percentage of participants |
| Standard of Care | Proportion of Participants With Objective Response | Investigator's assessment | 11.5 percentage of participants |
Comparison: Core radiology laboratory assessmentp-value: 0.962495% CI: [0.06, 1.71]Cochran-Mantel-Haenszel
Comparison: Investigator's assessmentp-value: 0.81495% CI: [0.27, 1.98]Cochran-Mantel-Haenszel
Secondary
Survival Probability at 1 Year
Probability that the participants will survive at end of 1 year from the first dose of study treatment. Calculated using data collected from baseline until death (up to 3 years after first dose of study medication). Probability calculated from Kaplan-Meier estimate.
Time frame: Baseline until death (up to 3 years after first dose of study medication)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib | Survival Probability at 1 Year | 0.376 ratio |
| Standard of Care | Survival Probability at 1 Year | 0.446 ratio |