Study Of SU011248 In Combination With Docetaxel And Trastuzumab In Patients With Advanced Breast Cancer HER-2 Positive

Study Overview
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Brief Summary
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This is an exploratory trial evaluating the tolerability and preliminary anti-tumor activity of SU011248 combined with docetaxel and trastuzumab in patients with locally recurrent or metastatic breast cancer over-expressing Her-2, who have not received chemotherapy treatment in the advanced disease setting.

Official Title
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An Explorative Study Of The Tolerability Of SU011248 In Combination With Docetaxel And Trastuzumab As First-Line Treatment In Patients With Breast Cancer Over-Expressing HER-2

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Herceptin
* Drug: Sunitinib
* 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. Tumors over-expressing Her-2 Candidate for treatment with docetaxel/trastuzumab Exclusion Criteria: Histology of inflammatory carcinoma AST and/or ALT >1.5 x ULN concomitant with ALP >2.5 x ULN

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>Combination of SU011248 (37.5 mg once daily [Schedule 2/1]) with docetaxel (75 mg/m2 every 3 weeks) and trastuzumab (therapeutic dose) | Drug: Herceptin<br>* Trastuzumab will be administered intravenously on Day 1 before docetaxel - loading dose of 4 mg/kg over 90-minute on Day 1 followed by weekly maintenance doses of 2 mg/kg on Days 1, 8, 15 given as 30-minute infusions if the initial loading dose was well tolerated. Loading dose of 8 mg/kg over 90-minute on Day 1 followed by 3-weekly maintenance doses of 6 mg/kg given as 90-minute infusions. The administration of 6 mg/kg will be repeated on Day 1 every 3 weeks.<br>* Other names: trastuzumab;Drug: Sunitinib<br>* SU011248 will be administered at 37.5 mg once daily for 2 weeks every 3 weeks (Schedule 2/1) starting from Day 2, when in combination with docetaxel. SU011248 will be administered at the starting dose of 37.5 mg daily in a continuous regimen when docetaxel is discontinued.<br>* Other names: Sutent;Drug: Taxotere<br>* The starting dose of docetaxel will be 75 mg/m2 every 3 weeks, administered on Day 1 of each cycle as a 1-hour IV infusion.<br>* Other names: docetaxel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. | From screening until 28 days post last dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Objective Response (OR) | Percentage of participants with objective response based 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. CR are defined as disappearance of all target lesions. PR are those with at least 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. | Baseline, assessed every 6 weeks starting from Day1 of Cycle 3 up to end of treatment (Day 1344) | 
| Progression-free Survival (PFS) | Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. 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). | Baseline, assessed every 6 weeks starting from Day1 of Cycle 3 up to end of treatment (Day 1344) | 
| Duration of Response (DR) | Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. 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 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response. | Baseline, assessed every 6 weeks starting from Day1 of Cycle 3 up to end of treatment (Day 1344) | 
| Plasma Trough Concentrations (Ctrough) of SU011248 (Sunitinib), SU012662 (Sunitinib Metabolite) and Total Drug (SU011248+SU012662) | Ctrough = the concentration prior to study medication administration. Ctrough was calculated for SU011248 (Sunitinib), SU012662 (Sunitinib metabolite) and total drug (SU011248+SU012662). Concentration values below the lower limit of quantification were taken as zero. | Pre-dose (0 hours [H]) on Day 1 and Day 15 of Cycle 2, 4, 6 and additionally Day 15 of Cycle 1 | 
| Maximum Observed Plasma Concentration (Cmax) of Docetaxel | Concentration values below the lower limit of quantification were taken as zero. | End of infusion (1 H) on Day 1 of Cycle 1, 2, 4 and 6 | 
| Plasma Trough Concentrations (Ctrough) of Trastuzumab | Ctrough = the concentration prior to study medication administration. | Weekly trastuzumab: Pre-dose (0 H) on Day 1 and 15 of Cycle 1, 2, 4 and 6; 3-weekly trastuzumab: Pre-dose (0 H) on Day 1 of Cycle 1, 2, 4 and 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer over-expressing HER2. First-line treatment with sunitinib/docetaxel/trastuzumab.