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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
26
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.
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.
Pfizer Investigational Site
Brussels, Belgium
Pfizer Investigational Site
Brussels, Belgium
Pfizer Investigational Site
Charleroi, Belgium
Pfizer Investigational Site
Sint-Niklaas, Belgium
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.
Time frame: From screening until 28 days post last dose of study drug
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.
Time frame: 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").
Time frame: Baseline, assessed every 6 weeks starting from Day1 of Cycle 3 up to end of treatment (Day 1344)
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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.
Pfizer Investigational Site
Wilrijk, Belgium
Pfizer Investigational Site
Meldola, FC, Italy
Pfizer Investigational Site
Milan, Italy
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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