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Study Of SU011248 In Combination With Docetaxel In Patients With Metastatic Breast Cancer

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00291577
Collaborator
(none)
22
Enrollment
3
Locations
1
Arm
31.1
Duration (Months)
7.3
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
22 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Exploratory Evaluation Of A Sequential Administration Of Docetaxel And SU011248 In Women With Advanced Breast Cancer
Study Start Date :
Jul 1, 2006
Actual Primary Completion Date :
Oct 1, 2008
Actual Study Completion Date :
Feb 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1

Drug: Sunitinib (Sutent)
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
Other Names:
  • Sutent

    • Drug: Taxotere
    Taxotere 75 mg/m2 iv, once every 3 weeks

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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).

    3. 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).

    4. 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.

    5. 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.

    6. 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.

    7. 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).

    8. 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.

    9. 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.

    10. 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.

    11. 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.

    12. 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.

    Secondary Outcome Measures

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Pfizer Investigational Site Bruxelles Belgium 1000
    2 Pfizer Investigational Site Milano Italy 20133
    3 Pfizer Investigational Site Stockholm Sweden 171 76

    Sponsors and Collaborators

    • Pfizer

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00291577
    Other Study ID Numbers:
    • A6181100
    First Posted:
    Feb 14, 2006
    Last Update Posted:
    Dec 23, 2009
    Last Verified:
    Nov 1, 2009
    Keywords provided by , ,
    advanced
    sunitinib (Sutent)
    docetaxel
    Phase 1B
    Additional relevant MeSH terms:
    Breast Neoplasms
    Docetaxel
    Sunitinib

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail First 12 subjects evaluable for pharmacokinetic (PK) analysis had full PK profile on Cycle 1, Day 1 (C1D1) and C2D1.
    Arm/Group Title Sunitinib in Combination With Docetaxel
    Arm/Group Description 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.
    Period Title: Overall Study
    STARTED 22
    COMPLETED 1
    NOT COMPLETED 21

    Baseline Characteristics

    Arm/Group Title Sunitinib in Combination With Docetaxel
    Arm/Group Description 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.
    Overall Participants 22
    Age, Customized (participants) [Number]
    18 to 44 years
    3
    13.6%
    45 to 64 years
    13
    59.1%
    > = 65 years
    6
    27.3%
    Sex: Female, Male (Count of Participants)
    Female
    21
    95.5%
    Male
    1
    4.5%

    Outcome Measures

    1. Primary Outcome
    Title Time to Reach Maximum Plasma Concentration (Tmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Sunitinib in Combination With Docetaxel
    Arm/Group Description 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.
    Measure Participants 11
    SU011248 C1D2
    6.0
    SU011248 C2D3
    6.0
    SU012662 C1D2
    6.0
    SU012662 C2D3
    6.0
    Total drug C1D2
    6.0
    Total drug C2D3
    6.0
    2. Primary Outcome
    Title Maximum Observed Plasma Concentration (Cmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Evaluable set of subjects for PK analysis
    Arm/Group Title Sunitinib in Combination With Docetaxel
    Arm/Group Description 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.
    Measure Participants 11
    SU011248 C1D2
    29.17
    (7.906)
    SU011248 C2D3
    29.49
    (7.910)
    SU012662 C1D2
    5.07
    (2.385)
    SU012662 C2D3
    5.91
    (2.251)
    Total drug C1D2
    34.05
    (9.312)
    Total drug C2D3
    34.69
    (8.941)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib in Combination With Docetaxel
    Comments 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.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Ratio of adjusted geometric means
    Estimated Value 98.89
    Confidence Interval () 90%
    80.34 to 121.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments Ratio percent (%) (Test/Reference) of adjusted geometric means; values have been back-transformed from the log scale.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sunitinib in Combination With Docetaxel
    Comments SU012662 C1D2 vs C2D3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Ratio of adjusted geometric means
    Estimated Value 81.96
    Confidence Interval () 90%
    59.76 to 112.41
    Parameter Dispersion Type:
    Value:
    Estimation Comments Ratio percent (%) (Test/Reference) of adjusted geometric means; values have been back-transformed from the log scale.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sunitinib in Combination With Docetaxel
    Comments Total drug C1D2 vs C2D3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Ratio of adjusted geometric means
    Estimated Value 97.81
    Confidence Interval () 90%
    80.44 to 118.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments Ratio percent (%) (Test/Reference) of adjusted geometric means; values have been back-transformed from the log scale.
    3. Primary Outcome
    Title 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
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Evaluable set of subjects for PK analysis
    Arm/Group Title Sunitinib in Combination With Docetaxel
    Arm/Group Description 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.
    Measure Participants 11
    SU011248 C1D2
    486.38
    (132.439)
    SU011248 C2D3
    479.80
    (128.718)
    SU012662 C1D2
    82.21
    (33.204)
    SU012662 C2D3
    96.88
    (30.513)
    Total drug C1D2
    568.78
    (152.106)
    Total drug C2D3
    567.43
    (145.952)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib in Combination With Docetaxel
    Comments SU011248 C1D2 vs C2D3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Ratio of adjusted geometric means
    Estimated Value 101.23
    Confidence Interval () 90%
    82.75 to 123.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments Ratio percent (%) (Test/Reference) of adjusted geometric means; values have been back-transformed from the log scale.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sunitinib in Combination With Docetaxel
    Comments SU012662 C1D2 vs C2D3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Ratio of adjusted geometric means
    Estimated Value 81.72
    Confidence Interval () 90%
    62.40 to 107.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments Ratio percent (%) (Test/Reference) of adjusted geometric means; values have been back-transformed from the log scale.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sunitinib in Combination With Docetaxel
    Comments Total drug C1D2 vs C2D3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Ratio of adjusted geometric means
    Estimated Value 100.00
    Confidence Interval () 90%
    82.95 to 120.56
    Parameter Dispersion Type:
    Value:
    Estimation Comments Ratio percent (%) (Test/Reference) of adjusted geometric means; values have been back-transformed from the log scale.
    4. Primary Outcome
    Title Area Under the Curve From Time 0 to Last Quantifiable Concentration (AUClast): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Evaluable set of subjects for PK analysis
    Arm/Group Title Sunitinib in Combination With Docetaxel
    Arm/Group Description 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.
    Measure Participants 0
    5. Primary Outcome
    Title Trough Plasma Concentration (Ctrough) at Time Zero (0): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Sunitinib in Combination With Docetaxel
    Arm/Group Description 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.
    Measure Participants 18
    SU011248 C1D15 (n=18)
    52.06
    (23.05)
    SU011248 C2D1 (n=11)
    5.00
    (5.14)
    SU012662 C1D15 (n=18)
    21.75
    (8.85)
    SU012662 C2D1 (n=11)
    4.88
    (3.52)
    Total drug C1D2 (n=12)
    0.20
    (0.00)
    Total drug C1D15 (n=18)
    73.81
    (29.00)
    Total drug 21D1 (n=11)
    9.87
    (8.36)
    6. Primary Outcome
    Title Time to Reach Maximum Plasma Concentration (Tmax): Docetaxel PK Parameters
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Evaluable set of subjects for PK analysis
    Arm/Group Title Sunitinib in Combination With Docetaxel
    Arm/Group Description 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.
    Measure Participants 10
    C1D1
    0.70
    C2D1
    0.77
    7. Primary Outcome
    Title Maximum Observed Plasma Concentration (Cmax): Docetaxel PK Parameters
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Evaluable set of subjects for PK analysis
    Arm/Group Title Sunitinib in Combination With Docetaxel
    Arm/Group Description 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.
    Measure Participants 10
    C1D1
    2932.00
    (903.952)
    C2D1
    2955.38
    (853.925)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib in Combination With Docetaxel
    Comments C1D1 vs C2D1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Ratio of adjusted geometric means
    Estimated Value 99.18
    Confidence Interval () 90%
    78.73 to 124.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments Ratio percent (%) (Test/Reference) of adjusted geometric means; values have been back-transformed from the log scale.
    8. Primary Outcome
    Title Area Under the Plasma Concentration-time Curve From Time Zero (0) to 24 Hours (AUC24): Docetaxel PK Parameters
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Evaluable set of subjects for PK analysis
    Arm/Group Title Sunitinib in Combination With Docetaxel
    Arm/Group Description 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.
    Measure Participants 10
    C1D1
    2918.09
    (594.227)
    C2D1
    3101.69
    (778.041)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib in Combination With Docetaxel
    Comments C1D1 vs C2D1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Ratio of adjusted geometric means
    Estimated Value 94.98
    Confidence Interval () 90%
    78.73 to 114.58
    Parameter Dispersion Type:
    Value:
    Estimation Comments Ratio percent (%) (Test/Reference) of adjusted geometric means; values have been back-transformed from the log scale.
    9. Secondary Outcome
    Title Progression-Free Survival (PFS) Based on Investigator Assessment
    Description 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

    Outcome Measure Data

    Analysis Population Description
    ITT population = all subjects enrolled in study who received at least 1 dose of study medication (SU011248 or docetaxel).
    Arm/Group Title Sunitinib in Combination With Docetaxel
    Arm/Group Description 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.
    Measure Participants 20
    Median (95% Confidence Interval) [weeks]
    34.9
    10. Secondary Outcome
    Title Number of Subjects With Objective Response of Complete Response or Partial Response Based on Investigator Assessment
    Description 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

    Outcome Measure Data

    Analysis Population Description
    ITT; subjects with baseline assessments
    Arm/Group Title Sunitinib in Combination With Docetaxel
    Arm/Group Description 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.
    Measure Participants 20
    Number [participants]
    14
    63.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib in Combination With Docetaxel
    Comments Overall confirmed objective response rate (CR + PR)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter rate (percent)
    Estimated Value 73.7
    Confidence Interval () 95%
    48.8 to 90.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Two-sided Confidence Interval (CI) (%) from exact method based on F distribution.
    11. Secondary Outcome
    Title Number of Subjects With Clinical Benefit of Complete Response, Partial Response, or Stable Disease Based on Investigator Assessment
    Description 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

    Outcome Measure Data

    Analysis Population Description
    ITT; subjects with baseline assessments
    Arm/Group Title Sunitinib in Combination With Docetaxel
    Arm/Group Description 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.
    Measure Participants 20
    Number [participants]
    17
    77.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib in Combination With Docetaxel
    Comments Clinical Benefit Rate (CR + PR + SD > = 24 weeks)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter rate (percent)
    Estimated Value 89.5
    Confidence Interval () 95%
    66.9 to 98.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Two-sided CI (%) from exact method based on F distribution.
    12. Secondary Outcome
    Title Duration of Tumor Response Based on Investigator Assessment
    Description 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

    Outcome Measure Data

    Analysis Population Description
    ITT; subgroup of subjects with objective disease response
    Arm/Group Title Sunitinib in Combination With Docetaxel
    Arm/Group Description 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.
    Measure Participants 14
    Median (95% Confidence Interval) [weeks]
    28.7
    13. Primary Outcome
    Title Area Under the Plasma Concentration-time Curve From Time Zero (0) to 48 Hours (AUC48): Docetaxel PK Parameters
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Evaluable set of subjects for PK analysis
    Arm/Group Title Sunitinib in Combination With Docetaxel
    Arm/Group Description 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.
    Measure Participants 10
    C1D1
    3167.53
    (658.124)
    C2D1
    3326.98
    (775.599)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib in Combination With Docetaxel
    Comments C1D1 vs C2D1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Ratio of adjusted geometric means
    Estimated Value 95.57
    Confidence Interval () 90%
    79.90 to 114.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments Ratio percent (%) (Test/Reference) of adjusted geometric means; values have been back-transformed from the log scale.
    14. Primary Outcome
    Title Area Under the Curve From Time 24 Hours to 48 Hours (AUC24_48) : Docetaxel PK Parameters
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Evaluable set of subjects for PK analysis
    Arm/Group Title Sunitinib in Combination With Docetaxel
    Arm/Group Description 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.
    Measure Participants 10
    C1D1
    249.45
    (108.911)
    C2D1
    225.29
    (96.657)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib in Combination With Docetaxel
    Comments C1D1 vs C2D1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Ratio of adjusted geometric means
    Estimated Value 112.39
    Confidence Interval () 90%
    81.05 to 155.85
    Parameter Dispersion Type:
    Value:
    Estimation Comments Ratio percent (%) (Test/Reference) of adjusted geometric means; values have been back-transformed from the log scale.
    15. Primary Outcome
    Title Area Under the Curve From Time 0 to Last Quantifiable Concentration (AUClast): Docetaxel PK Parameters
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Evaluable set of subjects for PK analysis
    Arm/Group Title Sunitinib in Combination With Docetaxel
    Arm/Group Description 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.
    Measure Participants 10
    C1D1
    3159.58
    (675.834)
    C2D1
    3304.48
    (769.011)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib in Combination With Docetaxel
    Comments C1D1 vs C2D1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Ratio of adjusted geometric means
    Estimated Value 95.79
    Confidence Interval () 90%
    79.82 to 114.96
    Parameter Dispersion Type:
    Value:
    Estimation Comments Ratio percent (%) (Test/Reference) of adjusted geometric means; values have been back-transformed from the log scale.
    16. Primary Outcome
    Title Plasma Elimination Half-life (t1/2): Docetaxel PK Parameters
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Evaluable set of subjects for PK analysis
    Arm/Group Title Sunitinib in Combination With Docetaxel
    Arm/Group Description 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.
    Measure Participants 9
    C1D1
    22.55
    (5.914)
    C2D1
    24.88
    (10.651)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Sunitinib in Combination With Docetaxel
    Arm/Group Description 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.
    All Cause Mortality
    Sunitinib in Combination With Docetaxel
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    Sunitinib in Combination With Docetaxel
    Affected / at Risk (%) # Events
    Total 11/22 (50%)
    Blood and lymphatic system disorders
    Febrile neutropenia 4/22 (18.2%)
    Leukopenia 1/22 (4.5%)
    Neutropenia 2/22 (9.1%)
    Gastrointestinal disorders
    Stomatitis 1/22 (4.5%)
    General disorders
    Fatigue 1/22 (4.5%)
    Oedema peripheral 1/22 (4.5%)
    Pyrexia 1/22 (4.5%)
    Hepatobiliary disorders
    Jaundice 1/22 (4.5%)
    Musculoskeletal and connective tissue disorders
    Back pain 1/22 (4.5%)
    Musculoskeletal pain 1/22 (4.5%)
    Nervous system disorders
    Cerebral haemorrhage 1/22 (4.5%)
    Headache 1/22 (4.5%)
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 1/22 (4.5%)
    Skin and subcutaneous tissue disorders
    Palmar-plantar erythrodysaesthesia syndrome 1/22 (4.5%)
    Petechiae 1/22 (4.5%)
    Other (Not Including Serious) Adverse Events
    Sunitinib in Combination With Docetaxel
    Affected / at Risk (%) # Events
    Total 21/22 (95.5%)
    Blood and lymphatic system disorders
    Febrile neutropenia 2/22 (9.1%)
    Neutropenia 10/22 (45.5%)
    Eye disorders
    Conjunctivitis 2/22 (9.1%)
    Lacrimation increased 3/22 (13.6%)
    Photopsia 2/22 (9.1%)
    Visual acuity reduced 2/22 (9.1%)
    Gastrointestinal disorders
    Abdominal distension 2/22 (9.1%)
    Abdominal pain upper 7/22 (31.8%)
    Diarrhoea 13/22 (59.1%)
    Dyspepsia 7/22 (31.8%)
    Glossodynia 2/22 (9.1%)
    Haemorrhoids 2/22 (9.1%)
    Nausea 11/22 (50%)
    Oral pain 3/22 (13.6%)
    Stomatitis 11/22 (50%)
    Vomiting 4/22 (18.2%)
    General disorders
    Asthenia 6/22 (27.3%)
    Chest discomfort 3/22 (13.6%)
    Chest pain 4/22 (18.2%)
    Face oedema 2/22 (9.1%)
    Fatigue 10/22 (45.5%)
    Local swelling 2/22 (9.1%)
    Mucosal inflammation 9/22 (40.9%)
    Oedema peripheral 2/22 (9.1%)
    Pain 3/22 (13.6%)
    Pyrexia 7/22 (31.8%)
    Infections and infestations
    Cystitis 2/22 (9.1%)
    Nasopharyngitis 6/22 (27.3%)
    Investigations
    Alanine aminotransferase 2/22 (9.1%)
    Electrocardiogram QT prolonged 2/22 (9.1%)
    Metabolism and nutrition disorders
    Anorexia 3/22 (13.6%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 4/22 (18.2%)
    Back pain 3/22 (13.6%)
    Bone pain 3/22 (13.6%)
    Myalgia 7/22 (31.8%)
    Pain in extremity 2/22 (9.1%)
    Nervous system disorders
    Dizziness 4/22 (18.2%)
    Dysgeusia 6/22 (27.3%)
    Headache 8/22 (36.4%)
    Paraesthesia 2/22 (9.1%)
    Peripheral sensory neuropathy 5/22 (22.7%)
    Psychiatric disorders
    Depression 3/22 (13.6%)
    Insomnia 3/22 (13.6%)
    Respiratory, thoracic and mediastinal disorders
    Cough 3/22 (13.6%)
    Dyspnoea 4/22 (18.2%)
    Epistaxis 6/22 (27.3%)
    Pharyngolaryngeal pain 7/22 (31.8%)
    Skin and subcutaneous tissue disorders
    Alopecia 12/22 (54.5%)
    Dry skin 3/22 (13.6%)
    Night sweats 2/22 (9.1%)
    Palmar-plantar erythrodysaesthesia syndrome 11/22 (50%)
    Petechiae 2/22 (9.1%)
    Pruritus generalised 3/22 (13.6%)
    Rash 5/22 (22.7%)
    Skin exfoliation 2/22 (9.1%)
    Skin hyperpigmentation 2/22 (9.1%)
    Swelling face 3/22 (13.6%)
    Vascular disorders
    Flushing 2/22 (9.1%)
    Hypertension 2/22 (9.1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Results Point of Contact

    Name/Title Pfizer ClinicalTrials.gov Call Center
    Organization Pfizer, Inc.
    Phone 1-800-718-1021
    Email ClinicalTrials.govCallCenter@pfizer.com
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00291577
    Other Study ID Numbers:
    • A6181100
    First Posted:
    Feb 14, 2006
    Last Update Posted:
    Dec 23, 2009
    Last Verified:
    Nov 1, 2009