Breast Neoplasms
Conditions
Keywords
advanced, sunitinib (Sutent), docetaxel, Phase 1B
Brief summary
This study is to evaluate the safety of SU011248 (Sunitinib/Sutent) in combination with docetaxel in patients with metastatic or locally recurrent breast cancer who have not received chemotherapy treatment in the advanced disease setting.
Interventions
Sunitinib (Sutent) 37.5 mg in schedule 2/1; Sunitinib (Sutent) 37.5 mg in continuous dosing (post discontinuation of axotere) and in accordance with Investigator decision
DRUGTaxotere
Taxotere 75 mg/m2 iv, once every 3 weeks
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Breast cancer with evidence of unresectable, locally recurrent or metastatic disease * Candidate for treatment with docetaxel
Exclusion criteria
* Prior chemotherapy in the advanced disease setting * Inflammatory breast cancer * HER2 positive disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Elimination Half-life (t1/2): Docetaxel PK Parameters | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose | Mean Thalf (t1/2) = terminal elimination half life; collected C1D1, C2D1. Paired observation. |
| Area Under the Plasma Concentration-time Curve From Time Zero (0) to 24 Hours (AUC24): Docetaxel PK Parameters | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose | Mean AUC24 = area under the plasma concentration-time profile from time 0 to 24 hours; collected C1D1, C2D1. Paired observation. |
| Area Under the Plasma Concentration-time Curve From Time Zero (0) to 48 Hours (AUC48): Docetaxel PK Parameters | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose | Mean AUC48 = area under the plasma concentration-time profile from time 0 to 48 hours; collected C1D1, C2D1. Paired observation. |
| Area Under the Curve From Time 24 Hours to 48 Hours (AUC24_48) : Docetaxel PK Parameters | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose | Mean AUC24\_48 = area under the plasma concentration-time profile from 24 to 48 hours; collected C1D1, C2D1. Paired observation. |
| Area Under the Curve From Time 0 to Last Quantifiable Concentration (AUClast): Docetaxel PK Parameters | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose | Mean AUClast = area under the plasma concentration-time profile from time 0 (predose) to the last measurable concentration; collected C1D1, C2D1. Paired observation. |
| Time to Reach Maximum Plasma Concentration (Tmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | 1, 2, 4, 6, 8, 12, 24 hours postdose | Median Tmax = time for maximum plasma concentration (Cmax) for SU011248, SU012662, and combined SU011248 and SU012662 (total drug); collected C1D2, C2D3. Paired observation. |
| Maximum Observed Plasma Concentration (Cmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | 1, 2, 4, 6, 8, 12, 24 hours postdose | Mean Cmax = maximum plasma concentration for SU011248, SU012662, and combined SU011248 and SU012662 (total drug) measured as nanograms per milliliter (ng/mL); collected C1D2, C2D3. Paired observation; Cmax dose corrected C2D3 (dose correction if predose concentrations of SU011248 or SU012662 were \> 5% of Cmax). |
| Area Under the Plasma Concentration-time Profile From Time Zero (0) to 24 Hours (AUC24): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | 1, 2, 4, 6, 8, 12, 24 hours postdose | Mean AUC24 = area under plasma concentration-time profile from time 0 to 24 hours for SU011248, SU012662, and combined SU011248 and SU012662 (total drug) measured in nanograms times hour per milliliter (ng\*hr/mL); collected C1D2, C2D3. Paired observation; AUC24 dose corrected C2D3 (dose correction if predose concentrations of SU011248 or SU012662 were \> 5% of Cmax). |
| Area Under the Curve From Time 0 to Last Quantifiable Concentration (AUClast): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | 1, 2, 4, 6, 8, 12, 24 hours postdose | Mean AUClast = area under the plasma concentration-time profile from time 0 (predose) to the last measurable concentration; collected C1D2, C2D3. Data did not allow calculation of AUClast; not summarized; AUC summarized in outcome measure: Area under the plasma concentration-time curve from time zero (0) to 24 hours (AUC24): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters. |
| Trough Plasma Concentration (Ctrough) at Time Zero (0): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | 0 hour postdose | Mean Ctrough=plasma concentration-time profile at time 0 (predose); collected C1D2, C1D15, and C2D1. Calculated by setting concentration values below the limit of quantification to zero. |
| Time to Reach Maximum Plasma Concentration (Tmax): Docetaxel PK Parameters | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose | Median Tmax = time to maximum plasma concentration (Cmax) for Docetaxel; collected C1D1, C2D1. Paired observation. |
| Maximum Observed Plasma Concentration (Cmax): Docetaxel PK Parameters | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose | Mean Cmax = maximum plasma concentration for Docetaxel; collected C1D1, C2D1. Paired observation; Cmax dose corrected (dose correction if predose concentrations of SU011248 or SU012662 were \> 5% of Cmax). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Objective Response of Complete Response or Partial Response Based on Investigator Assessment | First dose of study treatment until at least 4 weeks after confirmed response or partial response | Number of subjects with objective response based on Investigator assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. |
| Number of Subjects With Clinical Benefit of Complete Response, Partial Response, or Stable Disease Based on Investigator Assessment | First dose of study treatment until at least 24 weeks on study | Number of subjects with clinical benefit based on Investigator assessment of confirmed complete response (CR), partial response (PR), or stable disease (SD) according to RECIST for at least 24 weeks on study. |
| Duration of Tumor Response Based on Investigator Assessment | Start of first confirmed CR or PR to first confirmed progression or death | Median duration (50%) of tumor response based on Investigator assessment for a subgroup of subjects with objective disease response: who have not progressed or died due to any cause; with a response and subsequent progression or death due to any cause for duration of response (DR). DR defined as time from start of first documented objective tumor response (CR or PR) to first documented objective tumor progression or death due to any cause, whichever occurs first. DR calculated as (Weeks) = (the end date for DR minus first subsequent confirmed CR or PR plus 1) divided by 7. |
| Progression-Free Survival (PFS) Based on Investigator Assessment | First dose of study treatment until progressive disease | Median time (50 percent \[%\]) from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first; based on Investigator assessment. PFS calculated as (Weeks) = (first event date minus first dose date plus 1) divided by 7. |
Countries
Belgium, Italy, Sweden
Participant flow
Pre-assignment details
First 12 subjects evaluable for pharmacokinetic (PK) analysis had full PK profile on Cycle 1, Day 1 (C1D1) and C2D1.
Participants by arm
| Arm | Count |
|---|---|
| Sunitinib in Combination With Docetaxel Sunitinib (SU011248) orally (PO) for 2 weeks every 3 weeks (2 weeks on, then 1 week off = Schedule 2/1) starting on Day 2 (Cycle 2, Day 3 only for those subjects included in the Pharmacokinetic \[PK\] study); starting dose 37.5 milligrams (mg) daily (QD). Docetaxel (Taxotere) administered Day 1 of each cycle via intravenous (IV) infusion every 3 weeks; starting dose 75 mg/m2. | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lack of Efficacy | 14 |
| Overall Study | Other | 4 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Sunitinib in Combination With Docetaxel |
|---|---|
| Age, Customized 18 to 44 years | 3 participants |
| Age, Customized 45 to 64 years | 13 participants |
| Age, Customized > = 65 years | 6 participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 22 |
| serious Total, serious adverse events | 11 / 22 |
Outcome results
Primary
Area Under the Curve From Time 0 to Last Quantifiable Concentration (AUClast): Docetaxel PK Parameters
Mean AUClast = area under the plasma concentration-time profile from time 0 (predose) to the last measurable concentration; collected C1D1, C2D1. Paired observation.
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose
Population: Evaluable set of subjects for PK analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib in Combination With Docetaxel | Area Under the Curve From Time 0 to Last Quantifiable Concentration (AUClast): Docetaxel PK Parameters | C1D1 | 3159.58 ng*hr/mL | Standard Deviation 675.834 |
| Sunitinib in Combination With Docetaxel | Area Under the Curve From Time 0 to Last Quantifiable Concentration (AUClast): Docetaxel PK Parameters | C2D1 | 3304.48 ng*hr/mL | Standard Deviation 769.011 |
Comparison: C1D1 vs C2D190% CI: [79.82, 114.96]
Primary
Area Under the Curve From Time 0 to Last Quantifiable Concentration (AUClast): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters
Mean AUClast = area under the plasma concentration-time profile from time 0 (predose) to the last measurable concentration; collected C1D2, C2D3. Data did not allow calculation of AUClast; not summarized; AUC summarized in outcome measure: Area under the plasma concentration-time curve from time zero (0) to 24 hours (AUC24): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters.
Time frame: 1, 2, 4, 6, 8, 12, 24 hours postdose
Population: Evaluable set of subjects for PK analysis
Primary
Area Under the Curve From Time 24 Hours to 48 Hours (AUC24_48) : Docetaxel PK Parameters
Mean AUC24\_48 = area under the plasma concentration-time profile from 24 to 48 hours; collected C1D1, C2D1. Paired observation.
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose
Population: Evaluable set of subjects for PK analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib in Combination With Docetaxel | Area Under the Curve From Time 24 Hours to 48 Hours (AUC24_48) : Docetaxel PK Parameters | C1D1 | 249.45 ng*hr/mL | Standard Deviation 108.911 |
| Sunitinib in Combination With Docetaxel | Area Under the Curve From Time 24 Hours to 48 Hours (AUC24_48) : Docetaxel PK Parameters | C2D1 | 225.29 ng*hr/mL | Standard Deviation 96.657 |
Comparison: C1D1 vs C2D190% CI: [81.05, 155.85]
Primary
Area Under the Plasma Concentration-time Curve From Time Zero (0) to 24 Hours (AUC24): Docetaxel PK Parameters
Mean AUC24 = area under the plasma concentration-time profile from time 0 to 24 hours; collected C1D1, C2D1. Paired observation.
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose
Population: Evaluable set of subjects for PK analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib in Combination With Docetaxel | Area Under the Plasma Concentration-time Curve From Time Zero (0) to 24 Hours (AUC24): Docetaxel PK Parameters | C1D1 | 2918.09 ng*hr/mL | Standard Deviation 594.227 |
| Sunitinib in Combination With Docetaxel | Area Under the Plasma Concentration-time Curve From Time Zero (0) to 24 Hours (AUC24): Docetaxel PK Parameters | C2D1 | 3101.69 ng*hr/mL | Standard Deviation 778.041 |
Comparison: C1D1 vs C2D190% CI: [78.73, 114.58]
Primary
Area Under the Plasma Concentration-time Curve From Time Zero (0) to 48 Hours (AUC48): Docetaxel PK Parameters
Mean AUC48 = area under the plasma concentration-time profile from time 0 to 48 hours; collected C1D1, C2D1. Paired observation.
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose
Population: Evaluable set of subjects for PK analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib in Combination With Docetaxel | Area Under the Plasma Concentration-time Curve From Time Zero (0) to 48 Hours (AUC48): Docetaxel PK Parameters | C1D1 | 3167.53 ng*hr.mL | Standard Deviation 658.124 |
| Sunitinib in Combination With Docetaxel | Area Under the Plasma Concentration-time Curve From Time Zero (0) to 48 Hours (AUC48): Docetaxel PK Parameters | C2D1 | 3326.98 ng*hr.mL | Standard Deviation 775.599 |
Comparison: C1D1 vs C2D190% CI: [79.9, 114.32]
Primary
Area Under the Plasma Concentration-time Profile From Time Zero (0) to 24 Hours (AUC24): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters
Mean AUC24 = area under plasma concentration-time profile from time 0 to 24 hours for SU011248, SU012662, and combined SU011248 and SU012662 (total drug) measured in nanograms times hour per milliliter (ng\*hr/mL); collected C1D2, C2D3. Paired observation; AUC24 dose corrected C2D3 (dose correction if predose concentrations of SU011248 or SU012662 were \> 5% of Cmax).
Time frame: 1, 2, 4, 6, 8, 12, 24 hours postdose
Population: Evaluable set of subjects for PK analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib in Combination With Docetaxel | Area Under the Plasma Concentration-time Profile From Time Zero (0) to 24 Hours (AUC24): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | SU011248 C1D2 | 486.38 ng*hr/mL | Standard Deviation 132.439 |
| Sunitinib in Combination With Docetaxel | Area Under the Plasma Concentration-time Profile From Time Zero (0) to 24 Hours (AUC24): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | SU011248 C2D3 | 479.80 ng*hr/mL | Standard Deviation 128.718 |
| Sunitinib in Combination With Docetaxel | Area Under the Plasma Concentration-time Profile From Time Zero (0) to 24 Hours (AUC24): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | SU012662 C1D2 | 82.21 ng*hr/mL | Standard Deviation 33.204 |
| Sunitinib in Combination With Docetaxel | Area Under the Plasma Concentration-time Profile From Time Zero (0) to 24 Hours (AUC24): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | SU012662 C2D3 | 96.88 ng*hr/mL | Standard Deviation 30.513 |
| Sunitinib in Combination With Docetaxel | Area Under the Plasma Concentration-time Profile From Time Zero (0) to 24 Hours (AUC24): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | Total drug C1D2 | 568.78 ng*hr/mL | Standard Deviation 152.106 |
| Sunitinib in Combination With Docetaxel | Area Under the Plasma Concentration-time Profile From Time Zero (0) to 24 Hours (AUC24): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | Total drug C2D3 | 567.43 ng*hr/mL | Standard Deviation 145.952 |
Comparison: SU011248 C1D2 vs C2D390% CI: [82.75, 123.83]
Comparison: SU012662 C1D2 vs C2D390% CI: [62.4, 107.04]
Comparison: Total drug C1D2 vs C2D390% CI: [82.95, 120.56]
Primary
Maximum Observed Plasma Concentration (Cmax): Docetaxel PK Parameters
Mean Cmax = maximum plasma concentration for Docetaxel; collected C1D1, C2D1. Paired observation; Cmax dose corrected (dose correction if predose concentrations of SU011248 or SU012662 were \> 5% of Cmax).
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose
Population: Evaluable set of subjects for PK analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib in Combination With Docetaxel | Maximum Observed Plasma Concentration (Cmax): Docetaxel PK Parameters | C1D1 | 2932.00 ng/mL | Standard Deviation 903.952 |
| Sunitinib in Combination With Docetaxel | Maximum Observed Plasma Concentration (Cmax): Docetaxel PK Parameters | C2D1 | 2955.38 ng/mL | Standard Deviation 853.925 |
Comparison: C1D1 vs C2D190% CI: [78.73, 124.95]
Primary
Maximum Observed Plasma Concentration (Cmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters
Mean Cmax = maximum plasma concentration for SU011248, SU012662, and combined SU011248 and SU012662 (total drug) measured as nanograms per milliliter (ng/mL); collected C1D2, C2D3. Paired observation; Cmax dose corrected C2D3 (dose correction if predose concentrations of SU011248 or SU012662 were \> 5% of Cmax).
Time frame: 1, 2, 4, 6, 8, 12, 24 hours postdose
Population: Evaluable set of subjects for PK analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib in Combination With Docetaxel | Maximum Observed Plasma Concentration (Cmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | SU012662 C2D3 | 5.91 ng/mL | Standard Deviation 2.251 |
| Sunitinib in Combination With Docetaxel | Maximum Observed Plasma Concentration (Cmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | SU011248 C1D2 | 29.17 ng/mL | Standard Deviation 7.906 |
| Sunitinib in Combination With Docetaxel | Maximum Observed Plasma Concentration (Cmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | SU011248 C2D3 | 29.49 ng/mL | Standard Deviation 7.91 |
| Sunitinib in Combination With Docetaxel | Maximum Observed Plasma Concentration (Cmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | SU012662 C1D2 | 5.07 ng/mL | Standard Deviation 2.385 |
| Sunitinib in Combination With Docetaxel | Maximum Observed Plasma Concentration (Cmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | Total drug C1D2 | 34.05 ng/mL | Standard Deviation 9.312 |
| Sunitinib in Combination With Docetaxel | Maximum Observed Plasma Concentration (Cmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | Total drug C2D3 | 34.69 ng/mL | Standard Deviation 8.941 |
Comparison: SU011248 C1D2 vs C2D3. Due to the exploratory nature of the study, no statistical hypothesis testing was done since the primary purpose was to assess the tolerability of the combination of SU011248 with docetaxel.90% CI: [80.34, 121.73]
Comparison: SU012662 C1D2 vs C2D390% CI: [59.76, 112.41]
Comparison: Total drug C1D2 vs C2D390% CI: [80.44, 118.94]
Primary
Plasma Elimination Half-life (t1/2): Docetaxel PK Parameters
Mean Thalf (t1/2) = terminal elimination half life; collected C1D1, C2D1. Paired observation.
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose
Population: Evaluable set of subjects for PK analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib in Combination With Docetaxel | Plasma Elimination Half-life (t1/2): Docetaxel PK Parameters | C1D1 | 22.55 hours | Standard Deviation 5.914 |
| Sunitinib in Combination With Docetaxel | Plasma Elimination Half-life (t1/2): Docetaxel PK Parameters | C2D1 | 24.88 hours | Standard Deviation 10.651 |
Primary
Time to Reach Maximum Plasma Concentration (Tmax): Docetaxel PK Parameters
Median Tmax = time to maximum plasma concentration (Cmax) for Docetaxel; collected C1D1, C2D1. Paired observation.
Time frame: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose
Population: Evaluable set of subjects for PK analysis
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sunitinib in Combination With Docetaxel | Time to Reach Maximum Plasma Concentration (Tmax): Docetaxel PK Parameters | C1D1 | 0.70 hours |
| Sunitinib in Combination With Docetaxel | Time to Reach Maximum Plasma Concentration (Tmax): Docetaxel PK Parameters | C2D1 | 0.77 hours |
Primary
Time to Reach Maximum Plasma Concentration (Tmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters
Median Tmax = time for maximum plasma concentration (Cmax) for SU011248, SU012662, and combined SU011248 and SU012662 (total drug); collected C1D2, C2D3. Paired observation.
Time frame: 1, 2, 4, 6, 8, 12, 24 hours postdose
Population: Evaluable set of subjects for PK analysis is subjects in ITT population who completed sampling for PK profiles for both SU011248 and docetaxel; ITT population = all subjects enrolled in study who received at least 1 dose of study medication (SU011248 or docetaxel).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sunitinib in Combination With Docetaxel | Time to Reach Maximum Plasma Concentration (Tmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | SU011248 C1D2 | 6.0 hours |
| Sunitinib in Combination With Docetaxel | Time to Reach Maximum Plasma Concentration (Tmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | SU011248 C2D3 | 6.0 hours |
| Sunitinib in Combination With Docetaxel | Time to Reach Maximum Plasma Concentration (Tmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | SU012662 C1D2 | 6.0 hours |
| Sunitinib in Combination With Docetaxel | Time to Reach Maximum Plasma Concentration (Tmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | SU012662 C2D3 | 6.0 hours |
| Sunitinib in Combination With Docetaxel | Time to Reach Maximum Plasma Concentration (Tmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | Total drug C1D2 | 6.0 hours |
| Sunitinib in Combination With Docetaxel | Time to Reach Maximum Plasma Concentration (Tmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | Total drug C2D3 | 6.0 hours |
Primary
Trough Plasma Concentration (Ctrough) at Time Zero (0): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters
Mean Ctrough=plasma concentration-time profile at time 0 (predose); collected C1D2, C1D15, and C2D1. Calculated by setting concentration values below the limit of quantification to zero.
Time frame: 0 hour postdose
Population: Evaluable set of subjects for PK analysis; (n) = Number of observations above lower limit of quantification (NALQ). No participants analyzed for SU011248 C1D2 and SU012662 C1D2; standard deviation for Total drug C1D2 confirmed as 0.00 (median, minimum, and maximum = 0.20).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib in Combination With Docetaxel | Trough Plasma Concentration (Ctrough) at Time Zero (0): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | SU011248 C1D15 (n=18) | 52.06 ng/mL | Standard Deviation 23.05 |
| Sunitinib in Combination With Docetaxel | Trough Plasma Concentration (Ctrough) at Time Zero (0): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | SU011248 C2D1 (n=11) | 5.00 ng/mL | Standard Deviation 5.14 |
| Sunitinib in Combination With Docetaxel | Trough Plasma Concentration (Ctrough) at Time Zero (0): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | SU012662 C1D15 (n=18) | 21.75 ng/mL | Standard Deviation 8.85 |
| Sunitinib in Combination With Docetaxel | Trough Plasma Concentration (Ctrough) at Time Zero (0): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | SU012662 C2D1 (n=11) | 4.88 ng/mL | Standard Deviation 3.52 |
| Sunitinib in Combination With Docetaxel | Trough Plasma Concentration (Ctrough) at Time Zero (0): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | Total drug C1D2 (n=12) | 0.20 ng/mL | Standard Deviation 0 |
| Sunitinib in Combination With Docetaxel | Trough Plasma Concentration (Ctrough) at Time Zero (0): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | Total drug C1D15 (n=18) | 73.81 ng/mL | Standard Deviation 29 |
| Sunitinib in Combination With Docetaxel | Trough Plasma Concentration (Ctrough) at Time Zero (0): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters | Total drug 21D1 (n=11) | 9.87 ng/mL | Standard Deviation 8.36 |
Secondary
Duration of Tumor Response Based on Investigator Assessment
Median duration (50%) of tumor response based on Investigator assessment for a subgroup of subjects with objective disease response: who have not progressed or died due to any cause; with a response and subsequent progression or death due to any cause for duration of response (DR). DR defined as time from start of first documented objective tumor response (CR or PR) to first documented objective tumor progression or death due to any cause, whichever occurs first. DR calculated as (Weeks) = (the end date for DR minus first subsequent confirmed CR or PR plus 1) divided by 7.
Time frame: Start of first confirmed CR or PR to first confirmed progression or death
Population: ITT; subgroup of subjects with objective disease response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib in Combination With Docetaxel | Duration of Tumor Response Based on Investigator Assessment | 28.7 weeks |
Secondary
Number of Subjects With Clinical Benefit of Complete Response, Partial Response, or Stable Disease Based on Investigator Assessment
Number of subjects with clinical benefit based on Investigator assessment of confirmed complete response (CR), partial response (PR), or stable disease (SD) according to RECIST for at least 24 weeks on study.
Time frame: First dose of study treatment until at least 24 weeks on study
Population: ITT; subjects with baseline assessments
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib in Combination With Docetaxel | Number of Subjects With Clinical Benefit of Complete Response, Partial Response, or Stable Disease Based on Investigator Assessment | 17 participants |
Comparison: Clinical Benefit Rate (CR + PR + SD \> = 24 weeks)95% CI: [66.9, 98.7]
Secondary
Number of Subjects With Objective Response of Complete Response or Partial Response Based on Investigator Assessment
Number of subjects with objective response based on Investigator assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response.
Time frame: First dose of study treatment until at least 4 weeks after confirmed response or partial response
Population: ITT; subjects with baseline assessments
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib in Combination With Docetaxel | Number of Subjects With Objective Response of Complete Response or Partial Response Based on Investigator Assessment | 14 participants |
Comparison: Overall confirmed objective response rate (CR + PR)95% CI: [48.8, 90.9]
Secondary
Progression-Free Survival (PFS) Based on Investigator Assessment
Median time (50 percent \[%\]) from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first; based on Investigator assessment. PFS calculated as (Weeks) = (first event date minus first dose date plus 1) divided by 7.
Time frame: First dose of study treatment until progressive disease
Population: ITT population = all subjects enrolled in study who received at least 1 dose of study medication (SU011248 or docetaxel).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib in Combination With Docetaxel | Progression-Free Survival (PFS) Based on Investigator Assessment | 34.9 weeks |