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

Study Overview
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Brief Summary
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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.

Official Title
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Exploratory Evaluation Of A Sequential Administration Of Docetaxel And SU011248 In Women With Advanced Breast Cancer

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Drug: Sunitinib (Sutent)
* Drug: Taxotere


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Sunitinib (Sutent)<br>* 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<br>* Other names: Sutent;Drug: Taxotere<br>* Taxotere 75 mg/m2 iv, once every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 1, 2, 4, 6, 8, 12, 24 hours postdose | 
| 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). | 1, 2, 4, 6, 8, 12, 24 hours postdose | 
| 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). | 1, 2, 4, 6, 8, 12, 24 hours postdose | 
| 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. | 1, 2, 4, 6, 8, 12, 24 hours postdose | 
| 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. | 0 hour postdose | 
| 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. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose | 
| 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). | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose | 
| 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. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose | 
| 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. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose | 
| 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. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose | 
| 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. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose | 
| Plasma Elimination Half-life (t1/2): Docetaxel PK Parameters | Mean Thalf (t1/2) = terminal elimination half life; collected C1D1, C2D1. Paired observation. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | First dose of study treatment until progressive disease | 
| 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. | First dose of study treatment until at least 4 weeks after confirmed response or partial response | 
| 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. | First dose of study treatment until at least 24 weeks on study | 
| 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. | Start of first confirmed CR or PR to first confirmed progression or death | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced, sunitinib (Sutent), docetaxel, Phase 1B